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Nunez H, Nieto PA, Mars RA, Ghavami M, Sew Hoy C, Sukhum K. Early life gut microbiome and its impact on childhood health and chronic conditions. Gut Microbes 2025; 17:2463567. [PMID: 39916516 PMCID: PMC11810090 DOI: 10.1080/19490976.2025.2463567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 12/20/2024] [Accepted: 02/02/2025] [Indexed: 02/12/2025] Open
Abstract
The development of the gut microbiome is crucial to human health, particularly during the first three years of life. Given its role in immune development, disturbances in the establishment process of the gut microbiome may have long term consequences. This review summarizes evidence for these claims, highlighting compositional changes of the gut microbiome during this critical period of life as well as factors that affect gut microbiome development. Based on human and animal data, we conclude that the early-life microbiome is a determinant of long-term health, impacting physiological, metabolic, and immune processes. The early-life gut microbiome field faces challenges. Some of these challenges are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies. Other challenges are methodological: small sample sizes, lack of longitudinal studies, and poor control of confounding variables. To address these limitations, we advocate for more robust research methodologies to better understand the microbiome's role in health and disease. Improved methods will lead to more reliable microbiome studies and a deeper understanding of its impact on health outcomes.
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Affiliation(s)
- Harold Nunez
- Seeding Inc, DBA Tiny Health, Austin, Texas, USA
| | | | - Ruben A. Mars
- Seeding Inc, DBA Tiny Health, Austin, Texas, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
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2
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Jardon KM, Umanets A, Gijbels A, Trouwborst I, Hul GB, Siebelink E, Vliex LM, Bastings JJ, Argamasilla R, Chenal E, Venema K, Afman LA, Goossens GH, Blaak EE. Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity. Gut Microbes 2025; 17:2501185. [PMID: 40336254 PMCID: PMC12064058 DOI: 10.1080/19490976.2025.2501185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 02/24/2025] [Accepted: 04/29/2025] [Indexed: 05/09/2025] Open
Abstract
Insulin resistance (IR) is an early marker of cardiometabolic deterioration which may develop heterogeneously in key metabolic organs, including the liver (LIR) and skeletal muscle (MIR). This tissue-specific IR is characterized by distinct metabolic signatures, but the role of the gut microbiota in its etiology remains unclear. Here, we profiled the gut microbiota, its metabolites and the plasma metabolome in individuals with either a LIR or MIR phenotype (n = 233). We observed distinct microbial community structures LIR and MIR, and higher short-chain fatty acid (SCFA) producing bacteria, fecal SCFAs and branched-chain fatty acids and a higher postprandial plasma glucagon-like-peptide-1 response in LIR. In addition, we found variations in metabolome profiles and phenotype-specific associations between microbial taxa and functional metabolite groups. Overall, our study highlights association between gut microbiota and its metabolites composition with IR heterogeneity that can be targeted in precision-based strategies to improve cardiometabolic health. Clinicaltrials.gov registration: NCT03708419.
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Affiliation(s)
- Kelly M. Jardon
- TiFN, Wageningen, The Netherlands
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Alexander Umanets
- Centre for Healthy Eating & Food Innovation, Maastricht University Campus Venlo, Venlo, The Netherlands
- Chair Group Youth Food and Health, Faculty of Science and Engineering, Maastricht University Campus Venlo, Venlo, The Netherlands
| | - Anouk Gijbels
- TiFN, Wageningen, The Netherlands
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
| | - Inez Trouwborst
- TiFN, Wageningen, The Netherlands
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Gabby B. Hul
- TiFN, Wageningen, The Netherlands
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Els Siebelink
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
| | - Lars M.M. Vliex
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Jacco J.A.J. Bastings
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | | | | | - Koen Venema
- Centre for Healthy Eating & Food Innovation, Maastricht University Campus Venlo, Venlo, The Netherlands
| | - Lydia A. Afman
- TiFN, Wageningen, The Netherlands
- Division of Human Nutrition and Health, Wageningen University & Research, Wageningen, The Netherlands
| | - Gijs H. Goossens
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Ellen E. Blaak
- TiFN, Wageningen, The Netherlands
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
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3
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Afecto Gonçalves MJ, González-Fernández C, Greses S. Assessing the effect of temperature drop on a stable anaerobic fermentation for volatile fatty acids production. Bioengineered 2025; 16:2458369. [PMID: 39895564 PMCID: PMC11792825 DOI: 10.1080/21655979.2025.2458369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 01/13/2025] [Accepted: 01/16/2025] [Indexed: 02/04/2025] Open
Abstract
Anaerobic fermentation (AF) processes are sensitive to temperature fluctuations, which can influence the microbial activity and overall metabolic performances. Anaerobic reactors can face unforeseen temperature control failures, leading to instabilities in the process. The present study investigated the effect of two short-term temperature perturbations (down to 20°C and 15°C) on AF of food wastes (FWs). While 20°C did not exhibit a negative impact on AF performance maintaining the bioconversion yields over 40%, the reactor subjected to 15°C presented an acidogenic limitation, which decreased the bioconversion yields (36.4 ± 1.8%). As a result, 2.2 ± 0.5 g/L of succinic acid was accumulated in the reactor, being identified as a temperature failure indicator. Once the conditions were reestablished (operation temperature of 25ºC), the metabolic redundancies identified in the reactors allowed the AFs recovery to initial fermentation yields. 20°C was further tested as operational temperature resulting in stable bioconversion yield similar to the Control Reactor (43.2 ± 0.3%). These results showed the feasibility of conducting AF under low temperatures, indicating the potential of this technology to increase the cost-effectiveness of AF at psychrophilic conditions.
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Affiliation(s)
| | - Cristina González-Fernández
- Biotechnological Processes Unit, IMDEA Energy, Madrid, Spain
- Department of Chemical Engineering and Environmental Technology, School of Industrial Engineering, University of Valladolid, Valladolid, Spain
- Institute of Sustainable Processes, Valladolid, Spain
| | - Silvia Greses
- Biotechnological Processes Unit, IMDEA Energy, Madrid, Spain
- CALAGUA – Unidad Mixta UV-UPV, Department of Chemical Engineering, Universitat de València, Spain
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Steinert RE, Rehman A, Sadabad MS, Milanese A, Wittwer-Schegg J, Burton JP, Spooren A. Microbial micronutrient sharing, gut redox balance and keystone taxa as a basis for a new perspective to solutions targeting health from the gut. Gut Microbes 2025; 17:2477816. [PMID: 40090884 PMCID: PMC11913388 DOI: 10.1080/19490976.2025.2477816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 02/05/2025] [Accepted: 03/05/2025] [Indexed: 03/18/2025] Open
Abstract
In health, the gut microbiome functions as a stable ecosystem maintaining overall balance and ensuring its own survival against environmental stressors through complex microbial interaction. This balance and protection from stressors is maintained through interactions both within the bacterial ecosystem as well as with its host. As a consequence, the gut microbiome plays a critical role in various physiological processes including maintaining the structure and function of the gut barrier, educating the gut immune system, and modulating the gut motor, digestive/absorptive, as well as neuroendocrine system all of which are crucial for human health and disease pathogenesis. Pre- and probiotics, widely available and clinically established, offer various health benefits primarily by beneficially modulating the gut microbiome. However, their clinical outcomes can vary significantly due to differences in host physiology, diets, individual microbiome compositions, and other environmental factors. This perspective paper highlights emerging scientific insights into the importance of microbial micronutrient sharing, gut redox balance, keystone species, and the gut barrier in maintaining a diverse and functional microbial ecosystem, and their relevance to human health. We propose a novel approach that targets microbial ecosystems and keystone taxa performance by supplying microbial micronutrients in the form of colon-delivered vitamins, and precision prebiotics [e.g. human milk oligosaccharides (HMOs) or synthetic glycans] as components of precisely tailored ingredient combinations to optimize human health. Such a strategy may effectively support and stabilize microbial ecosystems, providing a more robust and consistent approach across various individuals and environmental conditions, thus, overcoming the limitations of current single biotic solutions.
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Affiliation(s)
- Robert E. Steinert
- Health, Nutrition & Care (HNC), Dsm-Firmenich, Kaiseraugst, Switzerland
- Department of Surgery and Transplantation, University Hospital Zurich (USZ) and University of Zurich (UZH), Zürich, Switzerland
| | - Ateequr Rehman
- Health, Nutrition & Care (HNC), Dsm-Firmenich, Kaiseraugst, Switzerland
| | | | - Alessio Milanese
- Data Science, Science & Research, Dsm-Firmenich, Delft, Netherlands
| | | | - Jeremy P. Burton
- Department of Microbiology and Immunology, The University of Western Ontario, London, Canada
| | - Anneleen Spooren
- Health, Nutrition & Care (HNC), Dsm-Firmenich, Kaiseraugst, Switzerland
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5
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Li B, Liang C, Xu B, Song P, Liu D, Zhang J, Gu H, Jiang F, Gao H, Cai Z, Zhang T. Extreme winter environment dominates gut microbiota and metabolome of white-lipped deer. Microbiol Res 2025; 297:128182. [PMID: 40252261 DOI: 10.1016/j.micres.2025.128182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 03/23/2025] [Accepted: 04/10/2025] [Indexed: 04/21/2025]
Abstract
Qinghai-Tibet Plateau (QTP) is marked by harsh environments that drive the evolution of unique nutrient metabolism mechanism in indigenous animal gut microbiotas. Yet, responses of these microbiotas to different extreme environments remain poorly understood. White-lipped deer (Przewalskium albirostris), a native endangered species in the QTP, serves as an ideal model to study how gut microbiotas adapt to season and human disturbances. Here, a multi-omics integrated analysis of 16S rRNA, metagenomics, and untargeted metabolomics was performed to investigate the composition, function, and metabolic characteristics of gut microbiota in White-lipped deer across different seasons and living environments. Our results revealed that extreme winter environment dominated the composition, function, and metabolism of gut microbiota in white-lipped deer. The white-lipped deer exhibited an enriched gut microbiota associated with producing short-chain fatty acids in winter, with core feature genera including norank_o_Rhodospirillales, Rikenellaceae_RC9_gut_group, and unclassified_c_Clostridia. However, potential pathogenic bacteria and few short-chain fatty acid producers, with core feature genera including norank_f_p-2534-18B5_gut_group, Cellulosilyticum, and Paeniclostridium, showed enrichment in captivity. Pathways associated with carbohydrate metabolism, amino acid metabolism, and immune regulation showed enrichment in winter group as an adaptation to the cold and food scarcity. Among these, Rikenellaceae_RC9_gut_group and unclassified_c_Clostridia contributed significantly to these metabolic pathways. The gut microbiota of white-lipped deer exhibited enrichment in pathways related to intestinal inflammation and enhanced immune regulation to alleviate the stress of captivity. Among these, norank_f_p-2534-18B5_gut_group contributed the most to these pathways. Butyric, valeric, and valproic acids were significantly more abundant in the winter group, while 3-hydroxybutyric and (S)-beta-aminoisobutyric acids were higher in the captive group. Furthermore, enriched metabolites and associated pathways in both groups further supported the inferences on metagenomic functions. This study confirms the key role of specific gut microbiota in adapting to high-altitude winters and anthropogenic disturbances, emphasizing its importance for environmental resilience in wild, high-altitude mammals.
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Affiliation(s)
- Bin Li
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China; Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, China
| | - Chengbo Liang
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China; Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, China
| | - Bo Xu
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China; Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, China
| | - Pengfei Song
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China; Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, China
| | | | | | - Haifeng Gu
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, China
| | - Feng Jiang
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, China
| | - Hongmei Gao
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, China
| | - Zhenyuan Cai
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, China.
| | - Tongzuo Zhang
- Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, China; Qinghai Provincial Key Laboratory of Animal Ecological Genomics, Xining, China.
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6
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Pandeya PR, Black IM, Karlen SD, Heiss C, Tseng YC, Downie AB, Azadi P, Schendel RR. Hempseed cell wall polysaccharides are dominated by linear xylans and cellulose: Comprehensive structural profiling of ten cultivars of industrial hemp, Cannabis sativa L. Carbohydr Polym 2025; 361:123635. [PMID: 40368561 DOI: 10.1016/j.carbpol.2025.123635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 04/10/2025] [Accepted: 04/21/2025] [Indexed: 05/16/2025]
Abstract
Hempseed is a rich source of dietary fiber; however, there has been limited research on the variability of carbohydrate composition in hempseed cell walls. The primary aim of this study was to conduct a comprehensive chemical and structural analysis of the cell wall polysaccharides in ten hempseed cultivars. Water-soluble polysaccharides (WSP) and water-insoluble residues (WIR) were isolated and subsequently analyzed for their monosaccharide composition using HPAEC-PAD, glycosyl linkage analysis using GC-MS, and structural characterization via NMR spectroscopy. All hempseed cultivars contained a high proportion of insoluble fibers and smaller amounts of soluble polysaccharides. Glucose and xylose were the most abundant components of the WIR fractions, while the WSP fractions contained abundant amounts of galactose, galacturonic acid, arabinose, rhamnose, and mannose. The results of linkage and spectroscopic analysis were consistent with the compositional analysis, identifying cellulose and acetylated linear xylans as primary components of WIR, and arabinogalactans, rhamnogalacturonans, heteromannans, xyloglucans, and arabinan as predominant in WSP. Overall, the study revealed a comparable cell wall structure among the analyzed hemp seed varieties. The high fiber content of whole hempseed-based ingredients presents significant potential for food manufacturers seeking to develop products with enhanced dietary fiber content, offering both functional and nutritional benefits for consumers.
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Affiliation(s)
- Prakash Raj Pandeya
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40546, USA
| | - Ian M Black
- Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA
| | - Steven D Karlen
- Department of Energy, Great Lakes Bioenergy Research Center, Wisconsin Energy Institute, University of Wisconsin-Madison, Madison, WI 53726, USA
| | - Christian Heiss
- Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA
| | - Yen-Chang Tseng
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40546, USA
| | - A Bruce Downie
- Department of Horticulture, University of Kentucky, Lexington, KY 40546-0312, USA
| | - Parastoo Azadi
- Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA
| | - Rachel R Schendel
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY 40546, USA.
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Lin M, Huang R, Li W, Peng H, Chen J, Qiu Y, Liu Y, Chen L. Dysbiosis of the gut micro-flora aggravates symptoms and accelerates disease progression in MASLD-IBD Co-morbid mice through host-microbial metabolic imbalance. Arch Biochem Biophys 2025; 769:110441. [PMID: 40320060 DOI: 10.1016/j.abb.2025.110441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 04/09/2025] [Accepted: 04/26/2025] [Indexed: 05/07/2025]
Abstract
Studies have shown that dysregulation of intestinal microbial structure and co-metabolic imbalance caused by diet and other factors play important role in MASLD and IBD. However, it is unclear how host-microbial interactions differ in the two diseases, and what potential impact they have on accelerating disease progression. Our study aims to find the disease characteristics in MASLD, IBD and their complication from the perspective of host-microbial metabolism. In our study, mouse models of MASLD, IBD, and MASLD-IBD induced by high-fat diet and dextran sulfate sodium. Detecting the pathological changes of colon and liver. Using 16s rRNA to screen out specific micro-flora, and UPLC-MS to monitor the changes of metabolites in feces. The micro-flora-metabolite co-expression network was constructed by Cytoscape software. The result showed that MASLD-IBD mice aggravate intestinal barrier damage, hepatic steatosis and fibrosis, immune inflammation and other pathological changes. In MASLD-IBD mice, the structural change of gut micro-flora is similar to IBD mice, which significantly reduced the abundance of Actinobacteriota, Desulfobacterota while increasing the abundance of Proteobacteria, and the metabolic disorder include nine metabolic pathways, such as tryptophan, bile acids and short-chain fatty acids, is similar to MASLD mice. Their co-expression network indicates that different specific micro-flora are closely related to the metabolic disorder and disease symptoms of MASLD-IBD mice. Analyzing the relationship between intestinal microbial dysregulation and hoetic co-metabolic imbalance is helpful to understand the mechanism of MASLD and IBD comorbidity, which suggesting that combined liver-gut therapy may be a new method for the treatment of MASLD-IBD complication.
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Affiliation(s)
- Minling Lin
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Ruiting Huang
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Wanyu Li
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Hui Peng
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Jun Chen
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Yongyi Qiu
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Yi Liu
- School of Chinese Medicine, Southern Medical University, Guangzhou, 510515, China.
| | - Lei Chen
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
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Hicks R, Gozal D, Ahmed S, Khalyfa A. Interplay between gut microbiota and exosome dynamics in sleep apnea. Sleep Med 2025; 131:106493. [PMID: 40203611 DOI: 10.1016/j.sleep.2025.106493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 03/19/2025] [Accepted: 03/29/2025] [Indexed: 04/11/2025]
Abstract
Sleep-disordered breathing (SDB) is characterized by recurrent reductions or interruptions in airflow during sleep, termed hypopneas and apneas, respectively. SDB impairs sleep quality and is linked to substantive health issues including cardiovascular and metabolic disorders, as well as cognitive decline. Recent evidence suggests a link between gut microbiota (GM) composition and sleep apnea. Indeed, GM, a community of microorganisms residing in the gut, has emerged as a potential player in various diseases, and several studies have identified associations between sleep apnea and GM diversity along with shifts in bacterial populations. Additionally, the concept of "leaky gut," a compromised intestinal barrier with potentially increased inflammation, has emerged as another key player in the potential bidirectional relationship between GM and sleep apnea. One of the potential effectors could be extracellular vesicles (EVs) underlying gut-brain communication pathways that are relevant to sleep regulation and function. Thus, therapeutic implications afforded by targeting the GM or exosomes for sleep apnea management have surfaced as promising areas of research. This review explores current understanding of the relationship between GM, exosomes and sleep apnea, highlighting key research dynamics and potential mechanisms. A comprehensive review of the literature was conducted, focusing on studies investigating GM composition, intestinal barrier function and gut-brain communication in relation to sleep apnea.
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Affiliation(s)
- Rebecca Hicks
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25755, USA
| | - David Gozal
- Department of Pediatrics and Office of the Dean, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25755, USA
| | - Sarfraz Ahmed
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25755, USA
| | - Abdelnaby Khalyfa
- Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25755, USA.
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Wen Y, Zhou Y, Xu J, Cui Q, Weng Z, Lin Y, Song H, Xiong L, Wang L, Zhao C, Shen X, Wang F. Structural characterization and fermentation of a novel Moringa oleifera leaves polysaccharide with hypoglycemic effects. Food Chem 2025; 479:143832. [PMID: 40090193 DOI: 10.1016/j.foodchem.2025.143832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 03/03/2025] [Accepted: 03/08/2025] [Indexed: 03/18/2025]
Abstract
Moringa oleifera leaf-derived natural products offer diverse health benefits in metabolic disorders. However, the structural attributes of M. oleifera leaf polysaccharides, their transformations during gastrointestinal digestion, and their influence on gut microbiota and hypoglycemic activity remain insufficiently understood. This study isolated and purified a hypoglycemic polysaccharide (MOP-3) from M. oleifera leaves, primarily composed of arabinose, rhamnose, and galactose, with a molecular weight of 2.019 × 104 Da. Structural analysis identified glycosidic linkages, including →2)-α-L-Fucp-(1→, →2)-α-L-Araf-(1→, →2)-α-L-Rhap-(1→, →3,6)-β-D-Galp-(1→, →6)-β-D-Glcp-(1→, →2)-α-D-Xylp-(1→, →2,4)-β-D-Manp-(1→, →2,3)-α-D-GalpA-6-OMe-(1→, and →4)-β-D-GlcpA-6-OMe-(1→. MOP-3 reshapes gut microbiota by decreasing Firmicutes while increasing Bacteroidetes and Proteobacteria, concurrently stimulating SCFA production, and enhancing GLP-1 secretion in STC-1 cells. The structural characterization and hypoglycemic properties of MOP-3 in this study provide a theoretical basis for further utilization of food polysaccharides.
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Affiliation(s)
- Yuxi Wen
- College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China; University of Vigo, Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Science, E32004 Ourense, Spain
| | - Yang Zhou
- College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing 210046, China
| | - Jiaxiang Xu
- College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing 210046, China
| | - Qi Cui
- College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing 210046, China
| | - Zebin Weng
- School of Chinese Medicine & School Hospital, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yajuan Lin
- School of Chinese Medicine & School Hospital, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Haizhao Song
- College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing 210046, China
| | - Ling Xiong
- College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing 210046, China
| | - Luanfeng Wang
- College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing 210046, China
| | - Chao Zhao
- College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China
| | - Xinchun Shen
- College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing 210046, China
| | - Fang Wang
- College of Food Science and Engineering/Collaborative Innovation Center for Modern Grain Circulation and Safety, Nanjing University of Finance and Economics, Nanjing 210046, China; Beth Israel Deaconess Medical Center/Harvard Medical School, Boston 02215, United States of America.
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10
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Liu R, Xi Y, Duan X, Zhao Y, Tian Z. Exerkine-mediated organ interactions: A new interpretation of exercise on cardiovascular function improvement. Life Sci 2025; 371:123628. [PMID: 40210118 DOI: 10.1016/j.lfs.2025.123628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 03/31/2025] [Accepted: 04/06/2025] [Indexed: 04/12/2025]
Abstract
Cardiovascular diseases impair the structure and function of distal organs, including the liver, skeletal muscle, kidney, and adipose tissue. Exercise stimulates the interaction between the cardiovascular system and distal organs that is important for disease rehabilitation and organ health. However, the mechanisms by which exercise improves cardiovascular function through exerkine-mediated organ crosstalk remain incompletely elucidated. We used cardiovascular, exercise, exerkines, skeletal muscle, liver, kidney, and adipose tissue as keywords to search for the relevant articles, sorted out the differences between different exercise types, summarized the functions of 17 exerkines, focused on reviewing and categorizing the molecular mechanisms of interactions between the cardiovascular system and remote organs. We also look forward to future research perspectives on exercise prevention and control of chronic metabolic diseases. The aim of this review is to provide a new theoretical basis for establishing clinical rehabilitation and exercise prescriptions for cardiovascular system diseases.
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Affiliation(s)
- Renhan Liu
- Laboratory of Exercise Intervention on Metabolic Syndrome, Brain-Heart Health and Education, Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi' an 710119, PR China
| | - Yue Xi
- Laboratory of Exercise Intervention on Metabolic Syndrome, Brain-Heart Health and Education, Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi' an 710119, PR China..
| | - Xinyan Duan
- Laboratory of Exercise Intervention on Metabolic Syndrome, Brain-Heart Health and Education, Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi' an 710119, PR China
| | - Yifei Zhao
- Laboratory of Exercise Intervention on Metabolic Syndrome, Brain-Heart Health and Education, Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi' an 710119, PR China
| | - Zhenjun Tian
- Laboratory of Exercise Intervention on Metabolic Syndrome, Brain-Heart Health and Education, Institute of Sports and Exercise Biology, Shaanxi Normal University, Xi' an 710119, PR China..
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11
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Cresci GAM. Understanding how foods and enteral feedings influence the gut microbiome. Nutr Clin Pract 2025; 40:555-574. [PMID: 40051043 PMCID: PMC12049572 DOI: 10.1002/ncp.11285] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 01/09/2025] [Accepted: 02/06/2025] [Indexed: 05/06/2025] Open
Abstract
The gut microbiome supports both gut and overall health. Diet is known to be one of the driving factors that influences the gut microbiome. The foods we eat, the dietary and nondietary components they contain, various food consumption patterns, and the ratio of nutrients consumed have been shown to impact gut microbiome composition and function. Studies indicate that many acute and chronic diseases are associated with alterations to the gut microbiome. There are many patients who rely on enteral tube feeding for their nutrition support. More recently, enteral tube feeding formulations of "real food" have become commercially available. However, little is known about how enteral tube feeding impacts the gut microbiome in patients requiring this specialized form of nutrition therapy. This review summarizes the existing evidence regarding the food sources of commonly consumed macronutrients and their impact on the gut microbiome. Also presented is what is known regarding "standard" and real food enteral formulations on the gut microbiome. Existing evidence is suggestive that real food enteral formulations positively impact the gut microbiome. Still, more research is needed on ready-to-feed formulations, particularly in patients with various clinical conditions, and how gut microbiome modulation impacts clinical outcomes.
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Affiliation(s)
- Gail A. M. Cresci
- Department of GastroenterologyHepatology, and Nutrition, Digestive Disease Institute, Cleveland ClinicClevelandOhioUSA
- Department of Inflammation and ImmunityLerner Research Institute, Cleveland ClinicClevelandOhioUSA
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12
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Iddrisu I, Monteagudo-Mera A, Poveda C, Shahzad M, Walton GE, Andrews SC. A review of the effect of iron supplementation on the gut microbiota of children in developing countries and the impact of prebiotics. Nutr Res Rev 2025; 38:229-237. [PMID: 38586996 DOI: 10.1017/s0954422424000118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2024]
Abstract
Iron is essential for many physiological functions of the body, and it is required for normal growth and development. Iron deficiency (ID) is the most common form of micronutrient malnutrition and is particularly prevalent in infants and young children in developing countries. Iron supplementation is considered the most effective strategy to combat the risk of ID and ID anaemia (IDA) in infants, although iron supplements cause a range of deleterious gut-related problems in malnourished children. The purpose of this review is to assess the available evidence on the effect of iron supplementation on the gut microbiota during childhood ID and to further assess whether prebiotics offer any benefits for iron supplementation. Prebiotics are well known to improve gut-microbial health in children, and recent reports indicate that prebiotics can mitigate the adverse gut-related effects of iron supplementation in children with ID and IDA. Thus, provision of prebiotics alongside iron supplements has the potential for an enhanced strategy for combatting ID and IDA among children in the developing world. However, further understanding is required before the benefit of such combined treatments of ID in nutritionally deprived children across populations can be fully confirmed. Such enhanced understanding is of high relevance in resource-poor countries where ID, poor sanitation and hygiene, alongside inadequate access to good drinking water and poor health systems, are serious public health concerns.
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Affiliation(s)
- Ishawu Iddrisu
- Rose Ward, Prospect Park Hospital, Berkshire Healthcare NHS Foundation Trust, Reading, RG30 4EJ, UK
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK
- School of Biological Sciences, University of Reading, Whiteknights, Reading, RG6 6EX, UK
| | - Andrea Monteagudo-Mera
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK
| | - Carlos Poveda
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK
| | - Muhammed Shahzad
- Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan
- Faculty of Dentistry, Zarqa University, Zarqa, 13110, Jordan
| | - Gemma E Walton
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK
| | - Simon C Andrews
- School of Biological Sciences, University of Reading, Whiteknights, Reading, RG6 6EX, UK
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13
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Palm CL, de Wit S, Gorter TM, Rienstra M, Vos MJ, Kema IP, van der Ley CP, Bakker SJL, Bakker BM, de Boer RA, van Veldhuisen DJ, Meijers WC, Westenbrink BD. Beyond the gut: Systemic levels of short-chain fatty acids are altered in patients with heart failure. Int J Cardiol 2025; 428:133124. [PMID: 40068788 DOI: 10.1016/j.ijcard.2025.133124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 02/24/2025] [Accepted: 03/05/2025] [Indexed: 03/15/2025]
Abstract
BACKGROUND & AIM The gut microbiome produces short-chain fatty acids (SCFAs), which serve as a substantial energy source and provide a link between the microbiome and (cardiac) metabolism. It has been demonstrated that the composition of the microbiome is altered in patients with heart failure (HF), but whether circulating levels of SCFAs are altered in HF is unknown. METHODS & RESULTS Serum concentrations of the SCFAs acetate, propionate, and butyrate were measured in 205 patients with HF and in 54 healthy controls, using isotope dilution liquid chromatography-tandem mass spectrometry. Of the patients with HF, 99 had HF with a reduced ejection fraction (HFrEF) and 106 had HF with mildly-reduced or preserved ejection fraction (HFmrEF/HFpEF). Healthy controls were age and sex matched to the HFrEF patients. Serum concentrations of acetate and propionate were significantly lower in patients with HF than in healthy controls, whereas butyrate levels were higher in patients with HF. Analyses by HF type revealed that acetate and propionate levels were lower in both HFrEF and HFpEF/HFmrEF patients in comparison to healthy controls. However, butyrate levels were observed to be lower in patients with HFmrEF/HFpEF in comparison to healthy controls, while they were higher in patients with HFrEF. CONCLUSIONS In patients with HF, serum levels of acetate and propionate are lower across the HF spectrum, whereas serum butyrate levels are elevated in HFrEF, but lower in HFmrEF/HFpEF. These alterations in SCFA profiles suggest a microbiome-driven metabolic dysregulation, which appears to differ between HF subtypes.
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Affiliation(s)
- C L Palm
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Institute of Clinical Chemistry and Laboratory Medicine, Oldenburg Clinic, University of Oldenburg, Germany
| | - S de Wit
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - T M Gorter
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - M Rienstra
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - M J Vos
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, the Netherlands
| | - I P Kema
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, the Netherlands
| | - C P van der Ley
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, the Netherlands
| | - S J L Bakker
- Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - B M Bakker
- Laboratory of Pediatrics, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - R A de Boer
- Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, the Netherlands
| | - D J van Veldhuisen
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - W C Meijers
- Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, the Netherlands
| | - B D Westenbrink
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
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14
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Lindsell HB, Williams NC, Magistro D, Corsetti M, Walton GE, Hunter KA. Could the Therapeutic Effect of Physical Activity on Irritable Bowel Syndrome Be Mediated Through Changes to the Gut Microbiome? A Narrative and Hypothesis Generating Review. Neurogastroenterol Motil 2025; 37:e70004. [PMID: 40026117 PMCID: PMC12075915 DOI: 10.1111/nmo.70004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 01/31/2025] [Accepted: 02/04/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is one of the most prevalent gastrointestinal (GI) disorders worldwide. Defined as a disorder of gut-brain interaction, its pathophysiology is still not completely clear. Consequently, current treatments primarily target symptoms rather than addressing the cause of the condition. The gut microbiome is increasingly acknowledged as central to IBS pathophysiology and, thus, may have therapeutic potential. Several national treatment guidelines recommend increasing physical activity for IBS management. AIMS This review summarises the evidence about the relationship between physical activity, IBS symptoms, and the gut microbiome, investigating the hypothesis that physical activity's therapeutic effects on IBS may be explained via modulation of the gut microbiome. RESULTS This review revealed that routine exercise was associated with a 15%-66% reduction in symptom severity and up to 41% enhanced QoL in IBS participants, and modulates the gut microbiome in healthy controls. DISCUSSION This review generates the hypothesis that routine physical activity may favorably alter gut microbiome composition in IBS to improve IBS symptomology. While a plausible hypothesis, research needs to confirm whether gut microbiome modulation is involved in physical activity associated IBS symptom relief. CONCLUSION Furthermore, the establishment of the most effective mode, duration, and intensity of physical activity for each sex and IBS-subtype is needed, with patient input during this process crucial to successfully translate science into practice.
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Affiliation(s)
- Hannah B. Lindsell
- Department of Sport, Health and Performance Enhancement (SHAPE) Research Centre, Department of Sport ScienceNottingham Trent UniversityNottinghamUK
| | - Neil C. Williams
- Department of Sport, Health and Performance Enhancement (SHAPE) Research Centre, Department of Sport ScienceNottingham Trent UniversityNottinghamUK
| | - Daniele Magistro
- Department of Sport, Health and Performance Enhancement (SHAPE) Research Centre, Department of Sport ScienceNottingham Trent UniversityNottinghamUK
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research CentreNottingham University Hospitals NHS Trust UK, School of MedicineNottinghamUK
| | - Gemma E. Walton
- Department of Food and Nutritional SciencesThe University of ReadingReadingUK
| | - Kirsty A. Hunter
- Department of Sport, Health and Performance Enhancement (SHAPE) Research Centre, Department of Sport ScienceNottingham Trent UniversityNottinghamUK
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15
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Qiu X, Zou Z, Lin T, Guo C, Lin D. Engineered Lactobacillus rhamnosus Producing 3-Hydroxybutyrate: A Dual-Action Therapeutic Strategy for Colon Cancer Cachexia. Biotechnol Bioeng 2025; 122:1574-1589. [PMID: 40055977 DOI: 10.1002/bit.28972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/11/2025] [Accepted: 02/28/2025] [Indexed: 05/13/2025]
Abstract
3-hydroxybutyrate (3-HB), an essential endogenous metabolite, shows significant therapeutic potential in several disease contexts. However, its clinical application has been hampered by limitations, such as adverse effects on the gut microbiota. This study introduces a genetically engineered strain of Lactobacillus rhamnosus GG (LGGK) that integrates the benefits of 3-HB production with the probiotic properties of LGG. Using a murine colon cancer cachexia (CAC) model, LGGK supplementation significantly improved survival, reduced tumor progression, and alleviated muscle wasting. LGGK restored gut microbial diversity, increased the abundance of beneficial bacteria, and increased the production of short-chain fatty acids while reducing harmful microbial populations. In addition, LGGK supplementation demonstrated anti-inflammatory effects, effectively reducing elevated pro-inflammatory cytokines in serum and skeletal muscle. These findings highlight LGGK as a dual-action therapeutic approach that utilizes the metabolic benefits of 3-HB and the gut-modulating properties of LGG. This innovation offers a promising strategy for the treatment of CAC and potentially other metabolic and inflammatory disorders, and highlights the potential of engineered probiotics in advanced therapeutic applications.
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Affiliation(s)
- Xu Qiu
- Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China
| | - Zhiyun Zou
- Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China
| | - Taijie Lin
- Shanghai Diglean Health Technology Development Co., Shanghai, China
| | - Chenyun Guo
- Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China
| | - Donghai Lin
- Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China
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16
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Zhou BY, Shi XY, Luo ZY, Pan ZQ, Gu HY, Liu Y, Shi XH, Wu ZQ. Predictive Analysis of Dental Caries Risk via Rapid Urease Activity Evaluation in Saliva Using a ZIF-8 Nanoporous Membrane. ACS Sens 2025. [PMID: 40396810 DOI: 10.1021/acssensors.4c03091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2025]
Abstract
Despite a decrease in the incidence of dental caries over the past four decades, it remains a widespread public health concern. The multifactorial etiology of dental caries complicates effective prevention and early intervention efforts, underscoring the need for the development of rapid predictive methods that account for multiple factors. In this study, we selected the activity of urease secreted by Streptococcus salivarius as a metabolic marker for dental caries. This activity was quantified by measuring the diffusion of hydroxide ions generated from the urease catalytic reaction on urea across a ZIF-8-modified nanoporous membrane. The choice of ZIF-8 was based on its preference in transporting hydroxide ions, enabling the accurate detection of urease activity at concentrations as low as 1 CFU/mL. Subsequently, we collected 287 saliva samples to determine the Michaelis constant (Km) of urease using this method. Logistic regression analysis revealed that both the Km of urease and the frequency of sugar intake are significant factors influencing the development of dental caries. Furthermore, we developed a machine learning methodology for identifying dental caries, achieving an accuracy rate of 81%. It is expected that increasing the sample size will further enhance the predictive accuracy of the model. This innovative approach provides valuable insights into early intervention strategies in the fight against dental caries.
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Affiliation(s)
- Bao-Yi Zhou
- Institute for Applied Research in Public Health, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China
| | - Xiao-Yan Shi
- Nantong Stomatological Hospital, Nantong, Jiangsu 226019, China
| | - Zhao-Ying Luo
- Institute for Applied Research in Public Health, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China
| | - Zhong-Qin Pan
- Institute for Applied Research in Public Health, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China
| | - Hai-Ying Gu
- Institute for Applied Research in Public Health, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China
| | - Yang Liu
- Institute for Applied Research in Public Health, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China
| | - Xin-He Shi
- Jingling Institute of Technology, Nanjing, Jiangsu 211169, China
| | - Zeng-Qiang Wu
- Institute for Applied Research in Public Health, School of Public Health, Nantong University, Nantong, Jiangsu 226019, China
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17
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Derbyshire EJ, Brameld JM, Wall BT, Thomas P, Arens U, Forde CG, Hall W, Glenn AJ, Hill TR, Paxman J. Is There a Specific Role for Fungal Protein Within Food Based Dietary Guidelines? A Roundtable Discussion. NUTR BULL 2025. [PMID: 40390196 DOI: 10.1111/nbu.70011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Revised: 04/09/2025] [Accepted: 04/17/2025] [Indexed: 05/21/2025]
Abstract
Expanding and aging populations, sustainability drivers and changing attitudes to the way we eat mean that there has been growing interest in non-animal derived protein food sources. Given this shift, there has been an uprise in consumer demand and commercial innovation of meat analogues and alternative protein food sources. The question, with a focus on fungal proteins, is where to best place them within Food-based Dietary Guidelines? A Nutrition Society Member-Led meeting was convened as a roundtable on 12th February 2024 to gather views on whether there is a specific role for fungal protein within Food-based Dietary Guidelines and how this role is best communicated. The intention of the roundtable was to establish areas of consensus or any disparities, and pinpoint future research directions. The roundtable format included three contextual presentations followed by discussions around seven core statements. A group of 11 experts from academia, policymaking and industry participated. There was agreement that health and sustainability research had advanced (for mycoprotein in particular). Subsequently, there is no reason to exclude fungal-derived proteins from Food-based Dietary Guidelines. The panel agreed on the need for an updated database on mycoprotein intakes in different countries along with long-term population studies comparing fungal, plant and meat sources against health and sustainability outcomes. The consensus was that fungal-derived mycoprotein could be represented within Food-based Dietary Guidelines, within a 'non-animal/non-meat' or 'other protein' sector, or as part of a generic protein diversification message.
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Affiliation(s)
| | | | | | | | - Ursula Arens
- Freelance Consultant and Writer (Nutrition and Dietetics), Islington, London, UK
| | - Ciarán G Forde
- Wageningen University and Research, Wageningen, the Netherlands
| | | | - Andrea J Glenn
- New York University & Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - Tom R Hill
- Newcastle University, Newcastle upon Tyne, UK
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18
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Fukumori C, Ken Kawassaki R, Daré RG, Lopes LB. Polymer-lipid hybrid microcarriers for oral codelivery of paclitaxel and tributyrin: development, optimization, and cytotoxicity in cells and spheroids of colorectal cancer. Int J Pharm 2025; 676:125549. [PMID: 40189171 DOI: 10.1016/j.ijpharm.2025.125549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 03/30/2025] [Accepted: 03/31/2025] [Indexed: 04/19/2025]
Abstract
Colorectal cancer (CRC) is the third most frequent cancer worldwide. Despite advances in treatment, conventional chemotherapy suffers from severe side effects and limited drug selectivity, highlighting the importance of alternative therapies. In this study, a polymer-lipid hybrid microcarrier was developed for oral co-administration of paclitaxel (PTX) and tributyrin (TB) as a novel approach for CRC therapy. The microcarrier was designed with a pH-sensitive polymeric shell that encapsulates drug-loaded nanostructured lipid carriers (NLC); shell dissolution at intestinal pH enables localized release of the NLC. The methodological approach employed an emulsion of vegetable oil and NLC as a template for polymer deposition. Multiple parameters were optimized, including polymers ratios, NLC dilution, acid concentration, and sonication time. Spherical hybrid particles with smooth surface and mean size of 1000 nm were obtained; PTX encapsulation efficiency was 99.9 ± 0.2 %, with a production yield of 97.2 ± 0.08 %. Drug release followed the Korsmeyer-Peppas kinetic model. Cytotoxic evaluation in human colorectal adenocarcinoma HCT-116 monolayers showed that PTX encapsulation increased cytotoxicity, lowering IC50 to 83.7 nM compared to 199.5 nM for free PTX. The addition of TB further improved cytotoxicity, reducing the IC50 to 60.8 nM. A similar potentiation cytotoxicity was observed in spheroids. The microcarrier induced reductions in colony formation, alterations in cell cytoskeleton, and led to a significant reduction in P-glycoprotein expression compared to its free form, suggesting its potential to help to overcome drug resistance. These results point to the promising applicability of the hybrid microcarrier as an innovative delivery system for oral administration of cytotoxic agents.
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Affiliation(s)
- Claudio Fukumori
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Rodrigo Ken Kawassaki
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil; Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo, SP, Brazil
| | - Regina G Daré
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Luciana B Lopes
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
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19
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Kanika, Kumar A, Ahmad A, Rahul, Kumar B, Mahajan S, Ali A, Kumar J, Ali N, Navik U, Parvez S, Khan R. Beta-Sitosterol-Conjugated Sinapic Acid-Engineered Nanoliposome: Biomucoadhesive and Enzyme-Responsive Targeted Oral Therapy in Ulcerative Colitis. ACS APPLIED MATERIALS & INTERFACES 2025; 17:27839-27857. [PMID: 40298241 DOI: 10.1021/acsami.5c02190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
Developing oral drug delivery systems is promising for ulcerative colitis (UC). However, the key challenges, including formulation degradation under harsh gastric conditions, poor targeting efficiency, and limited colonic residence, lead to poor therapeutic efficacy that still needs to be tackled. Effective treatment requires a safe, efficacious, enzyme- and pH-responsive, biomucoadhesive oral drug delivery system to overcome these challenges. Therefore, we have developed chitosan-armored 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) nanoliposomes amalgamated with synthesized beta-sitosterol-sinapic acid (Be-S) conjugate, further encapsulated with 3,4-methylenedioxy-β-nitrostyrene (MNS) as NLRP3 inhibitor, termed C@MN@DMBe-S, to overcome the limitation of free MNS and sinapic acid. Formulated by the thin-film hydration method and processed through extrusion, these unilamellar liposomes demonstrated structural stability and mucoadhesive properties due to chitosan coating. This configuration protected the nanoliposomes from the gastric acidic environment and allowed retention in the inflamed colon for 48 h. The enzyme-responsive C@MN@DMBe-S nanoliposome releases sinapic acid at the inflamed colonic site via esterase activity, providing sustained and controlled release of MNS. This synergistic action delivers antioxidant and anti-inflammatory effects while influencing the gut microbiota composition by releasing short-chain fatty acids. Moreover, therapeutic investigations revealed that C@MN@DMBe-S exhibited superior efficacy compared with free MNS when administered orally. The formulation effectively downregulated NF-κB, NLRP3, Caspase-1, and IL-1β expression while upregulating MUC5AC expression, indicating enhanced anti-inflammatory and protective effects and thereby promoting mucosal healing. In addition, C@MN@DMBe-S was found to regulate immune cell expression and effectively downregulate neutrophil infiltration. This armor- and enzyme-responsive strategy elucidates the impact of oral nanomedicines on mitigating UC and is demonstrated as an effective treatment.
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Affiliation(s)
- Kanika
- Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali 140306, Punjab, India
| | - Ajay Kumar
- Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali 140306, Punjab, India
| | - Anas Ahmad
- Julia McFarlane Diabetes Research Centre (JMDRC) and Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary AB T2N4N1, Canada
| | - Rahul
- Department of Chemistry, Malaviya National Institute of Technology, Jaipur 302017, Rajasthan, India
| | - Bhuvnesh Kumar
- Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali 140306, Punjab, India
| | - Shubham Mahajan
- Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali 140306, Punjab, India
| | - Aneesh Ali
- Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali 140306, Punjab, India
| | - Jattin Kumar
- Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali 140306, Punjab, India
| | - Nemat Ali
- Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Umashanker Navik
- Department of Pharmacology, Central University of Punjab, Bathinda Ghudda Punjab, Bathinda 151401, Punjab, India
| | - Suhel Parvez
- Department of Toxicology, School of Chemical & Life Sciences, Jamia Hamdard, New Delhi 110062, India
| | - Rehan Khan
- Chemical Biology Unit, Institute of Nano Science and Technology, Sector 81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali 140306, Punjab, India
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20
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Hsu CY, Ahmad I, Maya RW, Abass MA, Gupta J, Singh A, Joshi KK, Premkumar J, Sahoo S, Khosravi M. The potential therapeutic approaches targeting gut health in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a narrative review. J Transl Med 2025; 23:530. [PMID: 40350437 PMCID: PMC12066075 DOI: 10.1186/s12967-025-06527-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2025] [Accepted: 04/21/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disorder characterized by persistent fatigue and cognitive impairments, with emerging evidence highlighting the role of gut health in its pathophysiology. The main objective of this review was to synthesize qualitative and quantitative data from research examining the gut microbiota composition, inflammatory markers, and therapeutic outcomes of interventions targeting the microbiome in the context of ME/CFS. METHODS The data collection involved a detailed search of peer-reviewed English literature from January 1995 to January 2025, focusing on studies related to the microbiome and ME/CFS. This comprehensive search utilized databases such as PubMed, Scopus, and Web of Science, with keywords including "ME/CFS," "Gut-Brain Axis," "Gut Health," "Intestinal Dysbiosis," "Microbiome Dysbiosis," "Pathophysiology," and "Therapeutic Approaches." Where possible, insights from clinical trials and observational studies were included to enrich the findings. A narrative synthesis method was also employed to effectively organize and present these findings. RESULTS The study found notable changes in the gut microbiota diversity and composition in ME/CFS patients, contributing to systemic inflammation and worsening cognitive and physical impairments. As a result, various microbiome interventions like probiotics, prebiotics, specific diets, supplements, fecal microbiota transplantation, pharmacological interventions, improved sleep, and moderate exercise training are potential therapeutic strategies that merit further exploration. CONCLUSIONS Interventions focusing on the gut-brain axis may help reduce neuropsychiatric symptoms in ME/CFS by utilizing the benefits of the microbiome. Therefore, identifying beneficial microbiome elements and incorporating their assessments into clinical practice can enhance patient care through personalized treatments. Due to the complexity of ME/CFS, which involves genetic, environmental, and microbial factors, a multidisciplinary approach is also necessary. Since current research lacks comprehensive insights into how gut health might aid ME/CFS treatment, standardized diagnostics and longitudinal studies could foster innovative therapies, potentially improving quality of life and symptom management for those affected.
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Affiliation(s)
- Chou-Yi Hsu
- Thunderbird School of Global Management, Arizona State University, Tempe Campus, Phoenix, AZ, USA
| | - Irfan Ahmad
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | | | | | - Jitendra Gupta
- Institute of Pharmaceutical Research, GLA University, Mathura, India
| | - Abhayveer Singh
- Centre for Research Impact & Outcome, Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab, India
| | - Kamal Kant Joshi
- Department of Allied Science, Graphic Era Hill University, Dehradun, India
- Graphic Era (Deemed to Be University), Dehradun, Uttarakhand, India
| | - J Premkumar
- Department of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - Samir Sahoo
- Department of General Medicine, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, India
| | - Mohsen Khosravi
- Department of Psychiatry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
- Health Promotion Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
- Community Nursing Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
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21
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Oğuz E, Yılmaz Y, Güneş FE. The relationship between bacterial changes and dietary intervention in non-alcoholic fatty liver disease. Clin Nutr ESPEN 2025; 68:267-273. [PMID: 40345652 DOI: 10.1016/j.clnesp.2025.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 04/19/2025] [Accepted: 05/02/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND AND AIM This study aimed to investigate the levels of Faecalibacterium prausnitzii (F. prausnitzii) and Eubacterium rectale (E. rectale) in patients with non-alcoholic fatty liver disease (NAFLD) and evaluate the impact of dietary intervention on these bacterial populations. MATERIALS An interventional study was conducted with 38 NAFLD patients recruited from the Marmara University Gastroenterology Institute. Participants were divided into two groups: a diet intervention group (n = 21) and a control group (n = 17). The dietary intervention consisted of a balanced diet containing 50-55 % carbohydrates, 30-35 % fats, and 15-20 % protein. Fecal samples were collected at baseline and after six weeks for both groups, and bacterial quantification was performed via deoxyribonucleic acid (DNA) analysis of the fecal samples. RESULTS In the diet intervention group, a significant increase in E. rectale abundance was observed after six weeks (p = 0.008). Additionally, intakes of dietary fiber, vitamin E, vitamin C, and thiamine were significantly higher in the intervention group compared to the control group by the end of the study (p < 0.05). However, no significant changes were detected in F. prausnitzii levels in either group. CONCLUSION The findings demonstrate that dietary intervention can significantly increase E. rectale abundance in NAFLD patients, while F. prausnitzii levels remain unaffected. These results highlight the selective influence of dietary modifications on gut bacterial populations, offering potential implications for the management of NAFLD.
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Affiliation(s)
- Esma Oğuz
- Kırklareli University, Faculty of Health Sciences, Department of Nutrition and Dietetics, Kırklareli, Türkiye.
| | - Yusuf Yılmaz
- Recep Tayyip Erdoğan University, School of Medicine, Department of Gastroenterology, Rize, Türkiye
| | - Fatma Esra Güneş
- İstanbul Medeniyet University, Faculty of Health Sciences, Department of Nutrition and Dietetics, İstanbul, Türkiye
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22
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Sun M, De Cuyper A, Xu J, Quiévy A, Janssens GPJ. Exploring fecal microbial activity in zoo felids of varying body mass on a similar diet. BMC Microbiol 2025; 25:270. [PMID: 40329211 PMCID: PMC12057243 DOI: 10.1186/s12866-025-03981-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Accepted: 04/21/2025] [Indexed: 05/08/2025] Open
Abstract
Under human care, felids are typically fed similar diets, unlike wild counterparts whose diets vary by body mass and ecology. This study evaluated fecal microbiota and fermentation products in 18 zoo felids from Pairi Daiza Zoo, Belgium, grouped by body mass: under 100 kg ("small") and over 100 kg ("large"), with 9 animals in each group. Fresh feces were collected from the rectum under anesthesia. Microbial composition was assessed via 16S rRNA gene sequencing, while the fecal volatile fatty acids were quantified using gas chromatography. At the phylum level, regardless of body mass, the gut microbiota of zoo felids was predominantly composed of Firmicutes (61.7%), Actinobacteria (16.4%) and Bacteroidetes (12.5%). At the genus level, the most abundant genus was Clostridium sensu stricto 1 (15.9%), followed by Collinsella (15.7%). Although no significant differences in microbial composition or alpha diversity were found, beta diversity showed body mass influenced overall microbial structure. Smaller felids had significantly higher acetate levels than larger felids (p < 0.01). Additionally, acetate proportions were positively correlated with Clostridium sensu stricto 13 (r = 0.6, p < 0.01) and Peptoniphilus (r = 0.5, p < 0.05). These results show particular associations between body mass and the response of the intestinal microbiome to diet, suggesting that a uniform diet may not suit all felids under human care.
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Affiliation(s)
- Mengmeng Sun
- Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
| | - Annelies De Cuyper
- Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Jia Xu
- Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
- Department of Veterinary Medicine, Faculty of Agriculture, Jinhua University of Vocational Technology, Jinhua, China
| | | | - Geert P J Janssens
- Department of Veterinary and Biosciences, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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23
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Jiang M, Bianchi F, van den Bogaart G. Protonophore activity of short-chain fatty acids induces their intracellular accumulation and acidification. FEBS Lett 2025. [PMID: 40325954 DOI: 10.1002/1873-3468.70064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 03/27/2025] [Accepted: 04/13/2025] [Indexed: 05/07/2025]
Abstract
Short-chain fatty acids (SCFAs), produced by dietary fiber fermentation in the colon, play essential roles in cellular metabolism, with butyrate notably modulating immune responses and epigenetic regulation. Their production contributes to an acidic colonic environment where protonated SCFAs permeate membranes, leading to intracellular acidification and SCFA accumulation. Using our method to measure intracellular pH, we investigated how extracellular pH influences butyrate-induced acidification and immunomodulatory effects in human macrophages. Our data show that butyrate accumulates and acidifies cells at acidic extracellular pH due to the permeability of its protonated form. While inflammatory cytokine production was mildly influenced by extracellular pH, butyrate-induced histone acetylation exhibited a pH dependence, underscoring the importance of considering extracellular pH when assessing the SCFA's functions.
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Affiliation(s)
- Muwei Jiang
- Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands
| | - Frans Bianchi
- Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands
| | - Geert van den Bogaart
- Department of Molecular Immunology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, The Netherlands
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24
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Nagao T, Yokoyama Y, Abe T, Miyata K, Sugita S, Ogura A, Murata Y, Higaki E, Fujieda H, Asahara T, Shimizu Y, Ebata T. The Ratio of the Preoperative Fecal Short-Chain Fatty Acid to Lactic Acid Concentrations as a Predictor of Postoperative Infectious Complications After Esophagectomy. Ann Surg Oncol 2025:10.1245/s10434-025-17347-0. [PMID: 40314905 DOI: 10.1245/s10434-025-17347-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Accepted: 04/04/2025] [Indexed: 05/03/2025]
Abstract
BACKGROUND The ratio of the fecal short-chain fatty acid (SCFA) to lactic acid concentrations (APB-L ratio) is a useful indicator for the healthiness of the intestinal microenvironment. A recent study indicated that the low APB-L ratio can be a predictor of postoperative infectious complications (POICs) in patients undergoing pancreaticoduodenectomy. However, the predictive power of the APB-L ratio in other highly invasive surgeries, such as esophagectomy, is still unclear. This study investigated whether the APB-L ratio can be a sensitive predictor of POICs in patients undergoing esohpagectomy. METHODS A total of 129 patients undergoing esohpagectomy with gastric conduit reconstruction were included in this study. Preoperative fecal samples were analyzed for SCFA and lactic acid concentrations. The associations between clinical characteristics, POICs, and the APB-L ratio were analyzed. Preoperative and intraoperative risk factors for POICs were explored via multivariate logistic regression analysis. RESULTS Postoperative infectious complications were observed in 34 patients (26%), including surgical site infections in 18 patients (14%). A low APB-L ratio was significantly associated with higher POICs and surgical site infections risk (both p < 0.05). A low APB-L ratio was identified as an independent risk factor for POICs, with an odds ratio of 3.62 (95% confidence interval, 1.44-9.10, p = 0.006). CONCLUSIONS The APB-L ratio measured with preoperative fecal organic acid concentrations is useful to assess the risk of POICs for esohpagectomy. The results also imply the importance of maintaining a healthy intestinal metabolism (thus high APB-L ratio) to reduce POICs before highly invasive surgery.
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Affiliation(s)
- Takuya Nagao
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
- Department of Surgery, Division of Perioperative Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Tetsuya Abe
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kazushi Miyata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shizuki Sugita
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Atsushi Ogura
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuki Murata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Eiji Higaki
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hironori Fujieda
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takashi Asahara
- Yakult Central Institute, Yakult Honsho Co., Ltd., Tokyo, Japan
| | - Yasuhiro Shimizu
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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25
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Aya V, Pardo-Rodriguez D, Vega LC, Cala MP, Ramírez JD. Integrating metagenomics and metabolomics to study the gut microbiome and host relationships in sports across different energy systems. Sci Rep 2025; 15:15356. [PMID: 40316630 PMCID: PMC12048592 DOI: 10.1038/s41598-025-98973-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 04/16/2025] [Indexed: 05/04/2025] Open
Abstract
The gut microbiome plays a critical role in modulating host metabolism, influencing energy production, nutrient utilization, and overall physiological adaptation. In athletes, these microbial functions may be further specialized to meet the unique metabolic demands of different sports disciplines. This study explored the role of the gut microbiome in modulating host metabolism among Colombian athletes by comparing elite weightlifters (n = 16) and cyclists (n = 13) through integrative omics analysis. Fecal and plasma samples collected one month before an international event underwent metagenomic, metabolomic, and lipidomic profiling. Metagenomic analysis revealed significant microbial pathways, including L-arginine biosynthesis III and fatty acid biosynthesis initiation. Key metabolic pathways, such as phenylalanine, tyrosine, and tryptophan biosynthesis; arginine biosynthesis; and folate biosynthesis, were enriched in both athlete groups. Plasma metabolomics and lipidomics revealed distinct metabolic profiles and a separation between athlete types through multivariate models, with lipid-related pathways such as lipid droplet formation and glycolipid synthesis driving the differences. Notably, elevated carnitine, amino acid, and glycerolipid levels in weightlifters suggest energy system-specific metabolic adaptations. These findings underscore the complex relationship between the gut microbiota composition and metabolic responses tailored to athletic demands, laying the groundwork for personalized strategies to optimize performance. This research highlights the potential for targeted modulation of the gut microbiota as a basis for tailored interventions to support specific energy demands in athletic disciplines.
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Affiliation(s)
- Viviana Aya
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia
| | - Daniel Pardo-Rodriguez
- MetCore - Metabolomics Core Facility, Vice-Presidency for Research, Universidad de los Andes, Bogotá, Colombia
| | - Laura Camila Vega
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia
| | - Mónica P Cala
- MetCore - Metabolomics Core Facility, Vice-Presidency for Research, Universidad de los Andes, Bogotá, Colombia
| | - Juan David Ramírez
- Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia.
- Molecular Microbiology Laboratory, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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26
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Vella VR, Ainsworth-Cruickshank G, Luft C, Wong KE, Parfrey LW, Vogl AW, Holman PJ, Bodnar TS, Raineki C. Dysregulation of immune system markers, gut microbiota and short-chain fatty acid production following prenatal alcohol exposure: A developmental perspective. Neurochem Int 2025; 185:105952. [PMID: 39988283 DOI: 10.1016/j.neuint.2025.105952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/25/2025] [Accepted: 02/19/2025] [Indexed: 02/25/2025]
Abstract
Prenatal alcohol exposure (PAE) can severely impact fetal development, including alterations to the developing immune system. Immune perturbations, in tandem with gut dysbiosis, have been linked to brain and behavioral dysfunction, but this relationship is poorly understood in the context of PAE. This study takes an ontogenetic approach to evaluate PAE-induced alterations to brain and serum cytokine levels and both the composition and metabolic output of the gut microbiota. Using a well-established rat model of PAE, cytokine levels in the serum, prefrontal cortex, amygdala, and hypothalamus as well as gut microbiota composition and short-chain fatty acid (SCFA) levels were assessed at three postnatal (P) timepoints: P8 (infancy), P22 (weaning), and P38 (adolescence). Male PAE rats had increased cytokine levels in the amygdala and hypothalamus, but not prefrontal cortex, at P8. This altered neuroimmune function was not seen in the PAE females. The effect of PAE on central cytokine levels was reduced at P22/38, the same age at which PAE-induced alterations in serum cytokine levels emerge in both sexes. PAE reduced bacterial diversity in both sexes at P8, but only in females at P38, where a PAE-induced unique community composition emerged. Both sexes had alterations to specific bacterial taxa (e.g., Firmicutes), some of which are important in producing the SCFA butyric acid, which was decreased in PAE animals at P22. These results demonstrate that PAE leads to sex- and age-specific alterations in immune function, gut microbiota and SCFA production, highlighting the need to consider both age and sex in future work.
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Affiliation(s)
- Victoria R Vella
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada
| | | | - Carolina Luft
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada
| | - Kingston E Wong
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada
| | - Laura W Parfrey
- Department of Botany, University of British Columbia, British Columbia, Canada
| | - A Wayne Vogl
- Life Sciences Centre, Department of Cellular and Physiological Sciences, University of British Columbia, British Columbia, Canada
| | - Parker J Holman
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada
| | - Tamara S Bodnar
- Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada
| | - Charlis Raineki
- Department of Psychology, Brock University, St. Catharines, Ontario, Canada.
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27
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Zeng H, Safratowich BD, Liu Z, Bukowski MR. Resistant starch inhibits high-fat diet-induced oncogenic responses in the colon of C57BL/6 mice. J Nutr Biochem 2025; 139:109838. [PMID: 39788163 DOI: 10.1016/j.jnutbio.2025.109838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2024] [Revised: 12/20/2024] [Accepted: 01/03/2025] [Indexed: 01/12/2025]
Abstract
The beneficial effects of dietary fiber for colon health may be due to short chain fatty acids (SCFAs), such as butyrate, produced by colonic bacterial fermentation. In contrast, obesogenic diet induced obesity is linked to increased colon cancer incidence. We hypothesize that increasing fiber intake promotes healthy microbiome and reduces bacterial dysbiosis and oncogenic signaling in the colon of mice fed an obesogenic diet. About 5-week-old male C57BL/6 mice were assigned to 5 dietary groups (n=22/group) for 24 weeks:(1) AIN93G as a control diet (AIN); (2) a high fat diet (HFD, 45% energy fat); (3) HFD+5% resistant starch enriched dietary fiber (RSF) from maize; (4) HFD+10%RSF; or (5) HFD+20%RSF. Compared to the AIN group, mice receiving the HFD exhibited more than 15% increase in body mass and body fat composition irrespective of RSF dosage. However, the HFD+RSF groups exhibited an increase (>300%) of fecal butyrate but a decrease (>45%) of secondary bile acids in a RSF dose-dependent manner over the HFD group. Similarly, there were concomitant decreases (>25%) in pro-inflammatory plasma cytokines (TNFα, IL-6 and MCP-1), β-catenin and Ki67 protein staining in the colon of the HFD+20%RSF group relative to the HFD group. Furthermore, the abundance of colonic Proteobacteria, signatures of dysbiosis, was decreased (>63%) in a RSF dose-dependent manner compared to the HFD. Collectively, these data indicate that RSF not only increases butyrate but also reduces secondary bile acids, bacterial dysbiosis and β-catenin in the colon of mice fed a HFD.
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Affiliation(s)
- Huawei Zeng
- United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203.
| | - Bryan D Safratowich
- United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203
| | - Zhenhua Liu
- School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003
| | - Michael R Bukowski
- United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58203
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28
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Lu SSM, Rutegård M, Häggström C, Gylfe Å, Harlid S, Van Guelpen B. Prior antibiotics exposure is associated with an elevated risk of surgical site infections, including anastomotic leakage, after colon cancer but not rectal cancer surgery: A register-based study of 38,839 patients. Int J Cancer 2025; 156:1703-1715. [PMID: 39600222 PMCID: PMC11887011 DOI: 10.1002/ijc.35269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 11/07/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024]
Abstract
Gut microbiota composition has been implicated in surgical site complications after colorectal cancer surgery. Antibiotics affect gut microbiota, but evidence for a role in surgical site complications is inconclusive. We aimed to investigate use of prescription antibiotics during the years before surgery in relation to the risk of surgical site infections, including anastomotic leakage, within 30 days after surgery. Cardiovascular/neurological complications and the urinary antiseptic methenamine hippurate, for which there is no clear link with the microbiota, were used as negative controls. We conducted a patient cohort study using complete population data from Swedish national registers between 2005 and 2020. The final study population comprised 26,527 colon cancer and 12,312 rectal cancer cases with a 4.5 year exposure window. In colon cancer patients, antibiotics use was associated with a higher risk of surgical site infections (adjusted odds ratio (aOR) for any versus no use = 1.20, 95% confidence interval (CI) 1.10-1.33) and anastomotic leakage in particular (aOR =1.19, 95% CI 1.03-1.36), both with dose-response relationships for increasing cumulative antibiotics use (Ptrend = <0.001 and Ptrend = 0.047, respectively). Conversely, associations in rectal cancer patients, as well as for the negative controls cardiovascular/neurological complications and methenamine hippurate, were null. In conclusion, prescription antibiotics use up to 4.5 years before colorectal cancer surgery is associated with a higher risk of surgical site infections, including anastomotic leakage, after colon cancer but not rectal cancer surgery. These findings support a role for antibiotics-induced intestinal dysbiosis in surgical site infections.
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Affiliation(s)
- Sai San Moon Lu
- Department of Diagnostics and Intervention, OncologyUmeå UniversityUmeåSweden
- Department of Public Health and Clinical Medicine, Sustainable HealthUmeå UniversityUmeåSweden
| | - Martin Rutegård
- Department of Diagnostics and Intervention, SurgeryUmeå UniversityUmeåSweden
- Wallenberg Centre for Molecular MedicineUmeå UniversityUmeåSweden
| | - Christel Häggström
- Department of Diagnostics and Intervention, Registry Centre NorthUmeå UniversityUmeåSweden
| | - Åsa Gylfe
- Department of Clinical MicrobiologyUmeå UniversityUmeåSweden
- Umeå Centre for Microbial ResearchUmeå UniversityUmeåSweden
| | - Sophia Harlid
- Department of Diagnostics and Intervention, OncologyUmeå UniversityUmeåSweden
| | - Bethany Van Guelpen
- Department of Diagnostics and Intervention, OncologyUmeå UniversityUmeåSweden
- Wallenberg Centre for Molecular MedicineUmeå UniversityUmeåSweden
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29
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Sharma T, Ranawat P, Garg A, Rastogi P, Kaushal N. Short-chain fatty acids as a novel intervention for high-fat diet-induced metabolic syndrome. Mol Cell Biochem 2025; 480:3169-3184. [PMID: 39709317 DOI: 10.1007/s11010-024-05185-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 12/07/2024] [Indexed: 12/23/2024]
Abstract
Metabolic syndrome (MetS) is driven by a complex interplay of genetic, lifestyle, and dietary factors, leading to weight gain, insulin resistance, dyslipidemia, and chronic inflammation. Gut microbiota dysbiosis has been recently recognized as a key contributor to MetS, leading to advancements in gut microbiome-based interventions to improve health outcomes. Considering the unique challenges associated with the use of pre/probiotics, short-chain fatty acids (SCFA), also known as postbiotics, have emerged as promising therapeutic agents due to their role in modulating host metabolism and physiology. Considering this, the aim of the current study was to explore the therapeutic potential of SCFA (butyrate, propionate, and acetate) supplementation against a high-fat diet (HFD)-induced experimental model of MetS in male Wistar rats. Alterations in body weight, lipid profile, histopathology, and adipose tissue accumulation were assessed to establish SCFA-mediated amelioration of experimental MetS. Further, the enzymatic (GPx, Catalase, GR, and GST) and non-enzymatic (LPO, total ROS, and Redox ratio were evaluated. The results indicated that SCFA supplementation could effectively mitigate key features of MetS. A significant reduction in body weight gain and fasting blood glucose levels, along with markedly lowered triglycerides, total cholesterol, and LDL levels, with partial restoration of HDL levels was observed following SCFA supplementation. SCFA administration also attenuated MetS-associated hepatic damage as studied by histopathological investigation and analysis of liver function marker enzyme activities. Such ameliorative effects of SCFA against HFD-induced MetS were owed to potential redox modulation studied using enzymatic and non-enzymatic oxidative stress markers. In conclusion, the study's outcomes show that SCFA supplementation could potentially be used against managing MetS. It underscores the therapeutic potential of SCFA by placing them as a novel gut microbiome-based dietary approach to improve metabolic health and reduce the risk of MetS-associated complications. However, more detailed mechanistic explorations are warranted in the future, leading to their beneficial role in MetS contributing to holistic health outcomes.
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Affiliation(s)
- Tanvi Sharma
- Department of Biophysics, Panjab University, Chandigarh, 160014, India
| | - Pavitra Ranawat
- Department of Biophysics, Panjab University, Chandigarh, 160014, India
| | - Ayushi Garg
- Department of Biophysics, Panjab University, Chandigarh, 160014, India
| | - Pulkit Rastogi
- Department of Hematology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India
| | - Naveen Kaushal
- Department of Biophysics, Panjab University, Chandigarh, 160014, India.
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30
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Mangan M, Połtowicz K, Metges CC, Siwek M. Modulatory effects of in ovo delivery of galactooligosaccharide and Lactiplantibacillus plantarum on antioxidant capacity, gene expression, and selected plasma metabolite parameters of broiler chickens. J Appl Genet 2025; 66:421-434. [PMID: 39666172 PMCID: PMC12000254 DOI: 10.1007/s13353-024-00931-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 11/22/2024] [Accepted: 12/03/2024] [Indexed: 12/13/2024]
Abstract
A stable gut microbiota promotes a healthy gut and enhances immune function, antioxidant status, and metabolic activities in chickens. The present research work aimed to investigate the modulatory impacts of in ovo delivery of prebiotic and probiotic on oxidative stress, the intestinal transcriptome, and various plasma metabolites in chickens. Fertilized Ross 308 eggs were administered in ovo either with galactooligosaccharide (GOS) (3.5 mg/egg or Lactiplantibacillus plantarum (LP) 1 × 106/egg on the 12th day of egg incubation. Three hundred viable Ross 308 broiler hatching eggs in total were randomly assigned to four groups, namely, the negative control not injected group, the group receiving physiological saline injections as the positive control, GOS, and LP. The analysis of genes associated with immune functions, antioxidants, barrier functions, and free fatty acid receptors were determined via qPCR. The analysis of the selected plasma blood metabolites was performed automatically with Pentra C 400. The antioxidant capacity of the chickens' liver, breast muscle, and spleen was enhanced by the in ovo injection of GOS and LP. The immune-related gene expression levels were upregulated after in ovo stimulation with either GOS or LP which improved the gut health of broiler chickens. In addition, several genes related to gut barrier functions were upregulated, thus ensuring epithelial integrity. As for blood plasma metabolites, no adverse effects were observed. In summary, we report that in ovo stimulation with either GOS or LP stimulates the immune system and improves the antioxidant status and gut health of chickens with no negative impact on plasma blood metabolite indices.
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Affiliation(s)
- Modou Mangan
- Department of Animal Biotechnology and Genetics, Bydgoszcz University of Science and Technology (PBS), Mazowiecka 28, 85-084, Bydgoszcz, Poland.
| | - Katarzyna Połtowicz
- Department of Poultry Breeding, National Research Institute of Animal Production, Krakow-Ska 1, 32-083, Balice, Poland
| | - Cornelia C Metges
- Research Institute for Farm Animal Biology (FBN), Nutritional Physiology, Wilhelm-Stahl-Allee 2, 18196, Dummerstorf, Germany
| | - Maria Siwek
- Department of Animal Biotechnology and Genetics, Bydgoszcz University of Science and Technology (PBS), Mazowiecka 28, 85-084, Bydgoszcz, Poland
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31
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Greene LK, Andriatiavina T, Foss ED, Andriantsalohimisantatra A, Rivoharison TV, Rakotoarison F, Randriamboavonjy T, Yoder AD, Ratsoavina F, Blanco MB. The gut microbiome of Madagascar's lemurs from forest fragments in the central highlands. Primates 2025; 66:313-325. [PMID: 39976822 DOI: 10.1007/s10329-025-01182-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Accepted: 02/03/2025] [Indexed: 04/23/2025]
Abstract
The gut microbiome is now understood to play essential roles in host nutrition and health and has become a dominant research focus in primatology. Over the past decade, research has clarified the evolutionary traits that govern gut microbiome structure across species and the ecological traits that further influence consortia within them. Nevertheless, we stand to gain resolution by sampling hosts in understudied habitats. We focus on the lemurs of Madagascar's central highlands. Madagascar's highlands have a deep history as heterogeneous grassland-forest mosaics, but due to significant anthropogenic modification, have long been overlooked as lemur habitat. We collected fecal samples from Verreaux's sifakas (Propithecus verreauxi), common brown lemurs (Eulemur fulvus), and Goodman's mouse lemurs (Microcebus lehilahytsara) inhabiting two protected areas in the highlands and used amplicon sequencing to determine gut microbiome diversity and membership. As expected, the lemurs harbored distinct gut consortia tuned to their feeding strategies. Mouse lemurs harbored abundant Bifidobacterium and Alloprevotella that are implicated in gum metabolism, sifakas harbored abundant Lachnospiraceae that are implicated in leaf-fiber metabolism, and brown lemurs harbored diverse consortia with abundant WCBH1-41 that could be associated with frugivory in harsh seasons and habitats. Within brown lemurs, a suite of bacteria varied between seed-packed and leaf-packed feces, a proxy for dietary intakes, collected from the same group over days. Our results underscore the evolutionary and ecological factors that govern primate gut microbiomes. More broadly, we showcase the forests of Madagascar's central highlands as rich habitat for future research of lemur ecology and evolution.
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Affiliation(s)
- Lydia K Greene
- Department of Biology, Duke University, Durham, NC, USA.
- Duke Lemur Center, Duke University, Durham, NC, USA.
| | - Tsinjo Andriatiavina
- Department of Zoology and Animal Biodiversity, University of Antananarivo, Antananarivo, Madagascar
| | - Elissa D Foss
- Department of Biology, Duke University, Durham, NC, USA
| | | | | | | | | | - Anne D Yoder
- Department of Biology, Duke University, Durham, NC, USA
| | - Fanomezana Ratsoavina
- Department of Zoology and Animal Biodiversity, University of Antananarivo, Antananarivo, Madagascar
| | - Marina B Blanco
- Department of Biology, Duke University, Durham, NC, USA
- Duke Lemur Center, Duke University, Durham, NC, USA
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Aranda-Carrillo SG, Del Carmen Ramos-Sustaita L, Cárdenas-Castro AP, Gutiérrez-Sarmiento W, Sánchez-Burgos JA, Ruíz-Valdiviezo VM, Sáyago-Ayerdi SG. Microbiota modulation and microbial metabolites produced during the in vitro colonic fermentation of Psidium guajava species. Food Res Int 2025; 208:116228. [PMID: 40263797 DOI: 10.1016/j.foodres.2025.116228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 02/27/2025] [Accepted: 03/11/2025] [Indexed: 04/24/2025]
Abstract
The interaction between gut microbiota and its metabolites is a growing area of research. Therefore, this study analyzed the bioactive compound profile of the indigestible fraction (IF) from Psidium species and evaluated its effects on microbiota composition during in vitro colonic fermentation. Hydroxycinnamic acids, hydroxybenzoic acids, and ellagitannins were the predominant phenolic compounds, with P. friedrichsthalianum ('Cas') exhibiting the highest concentrations. During in vitro colonic fermentation, a reduction in bacterial genera such as Enterobacteriaceae and Klebsiella was observed, while Faecalibacterium, Oscillibacter, Dialister, and Ruminococcaceae positively correlated with phenolic microbial metabolites. These findings suggest that the IF of Psidium species modulates gut microbiota composition and potentially contributes to the production of beneficial metabolites during human colonic fermentation, reinforcing the role of whole fruit consumption as a comprehensive matrix of nutrients and bioactive compounds beneficial to gut health.
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Affiliation(s)
- Suecia Grissol Aranda-Carrillo
- Tecnológico Nacional de México/ Instituto Tecnológico de Tepic, Av. Tecnológico No 2595, Col. Lagos del Country, CP 63175 Tepic, Nayarit, Mexico
| | - Lourdes Del Carmen Ramos-Sustaita
- Tecnológico Nacional de México/Instituto Tecnológico de Tuxtla-Gutiérrez, Departamento de Ingeniería Química y Bioquímica, Laboratory of Molecular Biology, Carretera Panamericana km 1080, CP 29050 Tuxtla Gutiérrez, Chiapas, Mexico
| | - Alicia Paulina Cárdenas-Castro
- Tecnológico Nacional de México/ Instituto Tecnológico de Tepic, Av. Tecnológico No 2595, Col. Lagos del Country, CP 63175 Tepic, Nayarit, Mexico
| | - Wilbert Gutiérrez-Sarmiento
- Chiapas Medicinal Plant Research Center, Pharmacobiology Experimental Laboratory, Autonomus University of Chiapas, Tuxtla Gutierrez, Chiapas, Mexico
| | - Jorge Alberto Sánchez-Burgos
- Tecnológico Nacional de México/ Instituto Tecnológico de Tepic, Av. Tecnológico No 2595, Col. Lagos del Country, CP 63175 Tepic, Nayarit, Mexico
| | - Víctor Manuel Ruíz-Valdiviezo
- Tecnológico Nacional de México/Instituto Tecnológico de Tuxtla-Gutiérrez, Departamento de Ingeniería Química y Bioquímica, Laboratory of Molecular Biology, Carretera Panamericana km 1080, CP 29050 Tuxtla Gutiérrez, Chiapas, Mexico
| | - Sonia Guadalupe Sáyago-Ayerdi
- Tecnológico Nacional de México/ Instituto Tecnológico de Tepic, Av. Tecnológico No 2595, Col. Lagos del Country, CP 63175 Tepic, Nayarit, Mexico.
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Dong Z, Zhang R, Shen L, Ji H, He H, Ji X, Zhao L. Gut Microbiota and Immunoglobulin A Nephropathy: Exploration of Dietary Intervention and Treatment Strategies. Food Sci Nutr 2025; 13:e70218. [PMID: 40321610 PMCID: PMC12045934 DOI: 10.1002/fsn3.70218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 04/16/2025] [Accepted: 04/17/2025] [Indexed: 05/08/2025] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is a primary glomerular disease characterized by the deposition of IgA. The pathogenesis of it is related to the dysbiosis of gut microbiota. Dysbiosis of gut microbiota influences mucosal immune response and systemic immune system, leading to glycosylation-deficient IgA1 (Gd-IgA1) increasing, which promotes the development of IgAN. Diet plays an important role in regulating gut microbiota and treating IgAN. In this review, we summarize the interplay between gut microbiota and IgAN, and their underlying mechanisms. We also describe the effects of dietary intake on IgAN, as well as the composition of gut microbiota. The progress on IgAN treatment mainly focuses on inhibiting or regulating the immune system. Moreover, therapeutic strategies related to gut microbiota such as dietary intervention, supplement of probiotics and prebiotics, as well as fecal microbiota transplantation (FMT) have shown the possibility of improving IgAN prognosis. Thus, exploration of the gut-kidney axis, the long-term effects of diet and microbiome is necessary to develop more effective treatment strategies.
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Affiliation(s)
- Zhaoyang Dong
- State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiChina
| | - Ran Zhang
- State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiChina
| | - Liang Shen
- Institute of Food and Drug Research for One Health, School of Food EngineeringLudong UniversityYantaiPeople's Republic of China
| | - Hong‐Fang Ji
- Institute of Food and Drug Research for One Health, School of Food EngineeringLudong UniversityYantaiPeople's Republic of China
| | - Haidong He
- Department of NephrologyMinhang Hospital, Fudan UniversityShanghaiChina
| | - Xiaoguo Ji
- State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiChina
- Shanghai Frontiers Science Centre of Optogenetic Techniques for Cell Metabolism, School of PharmacyEast China University of Science and TechnologyShanghaiChina
| | - Liming Zhao
- State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiChina
- Shanghai Collaborative Innovation Centre for Biomanufacturing Technology (SCICBT)ShanghaiChina
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Morales G, Bugueño C, Valenzuela R, Chamorro R, Leiva C, Gotteland M, Trunce-Morales S, Pizarro-Aranguiz N, Durán-Agüero S. Association between cheese consumption but not other dairy products and lower obesity risk in adults. PLoS One 2025; 20:e0320633. [PMID: 40299899 PMCID: PMC12040181 DOI: 10.1371/journal.pone.0320633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 02/21/2025] [Indexed: 05/01/2025] Open
Abstract
INTRODUCTION Some studies have associated dairy consumption with a lower risk of obesity. However, these studies are concentrated in developed countries with high dairy consumption. In developing countries, the evidence is scarce. This study aimed to evaluate the association between the consumption of different types of dairy products and obesity in Chilean adults. MATERIALS AND METHODS A cross-sectional study, stratified by sex and age, was carried out using a validated online survey to assess the consumption of dairy products among adults living in Chile. Dairy product consumption was then classified into tertiles. Obesity was determined based on self-reported body mass index (BMI) ≥ 30 kg/m2. Logistic regression models were used to assess the association between dairy consumption and obesity, adjusting for several confounding variables. RESULTS In total, 2008 participants were included in the analyses. Forty-seven percent, 39% and 14% belonged to the <35 years, 35-60 years, and ≥60-year groups, respectively. 55% were female, 86% had a low-medium socioeconomic level. Cow-derived cheese, milk, and yogurt were the most commonly consumed dairy products. Obese participants had a lower total consumption of dairy products (17.1%) than normal-weight subjects (25.7%, p<0.05). Higher cheese intake was significantly associated with a lower obesity risk (ORadj: 0.70; 95%CI 0.51-0.96, p<0.05). Other types of dairy products and total consumption of dairy products were not significantly associated. DISCUSSION AND CONCLUSIONS Habitual cheese consumption, but not other dairy products, was associated with a lower risk of obesity in this sample of Chilean adults.
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Affiliation(s)
- Gladys Morales
- Departamento de Salud Pública, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile
- Centro de Investigación en Epidemiología Cardiovascular y Nutricional (EPICYN), Universidad de La Frontera, Temuco, Chile
| | - Claudia Bugueño
- Departamento de clínica, Facultad de Medicina, Universidad Católica del Norte, Coquimbo, Chile
| | - Rodrigo Valenzuela
- Departamento de Nutrición, Facultad de Medicina, Universidad de Chile. Avenida Independencia. Independencia, Santiago, Chile
| | - Rodrigo Chamorro
- Departamento de Nutrición, Facultad de Medicina, Universidad de Chile. Avenida Independencia. Independencia, Santiago, Chile
| | - Carla Leiva
- Departamento de Nutrición y Dietética, Escuela de Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile, San Joaquín, Chile
| | - Martin Gotteland
- Departamento de Nutrición, Facultad de Medicina, Universidad de Chile. Avenida Independencia. Independencia, Santiago, Chile
| | - Silvana Trunce-Morales
- Carrera de Nutrición y Dietética, Departamento de Salud, Universidad de Los Lagos, Osorno, Chile
| | | | - Samuel Durán-Agüero
- Escuela de Nutrición y Dietética, Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebastián, Los Leones, Chile
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Nazir A, Hussain FHN, Nadeem Hussain TH, Al Dweik R, Raza A. Therapeutic targeting of the host-microbiota-immune axis: implications for precision health. Front Immunol 2025; 16:1570233. [PMID: 40364844 PMCID: PMC12069365 DOI: 10.3389/fimmu.2025.1570233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 03/24/2025] [Indexed: 05/15/2025] Open
Abstract
The human body functions as a complex ecosystem, hosting trillions of microbes that collectively form the microbiome, pivotal in immune system regulation. The host-microbe immunological axis maintains homeostasis and influences key physiological processes, including metabolism, epithelial integrity, and neural function. Recent advancements in microbiome-based therapeutics, including probiotics, prebiotics and fecal microbiota transplantation, offer promising strategies for immune modulation. Microbial therapies leveraging microbial metabolites and engineered bacterial consortia are emerging as novel therapeutic strategies. However, significant challenges remain, including individual microbiome variability, the complexity of host-microbe interactions, and the need for precise mechanistic insights. This review comprehensively examines the host microbiota immunological interactions, elucidating its mechanisms, therapeutic potential, and the future directions of microbiome-based immunomodulation in human health. It will also critically evaluate challenges, limitations, and future directions for microbiome-based precision medicine.
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Affiliation(s)
- Asiya Nazir
- Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates
| | | | | | - Rania Al Dweik
- Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates
| | - Afsheen Raza
- Department of Biomedical Sciences, College of Health Sciences, Abu Dhabi University, Abu Dhabi, United Arab Emirates
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Ren Y, He X, Wang L, Chen N. Comparison of the gut microbiota in older people with and without sarcopenia: a systematic review and meta-analysis. Front Cell Infect Microbiol 2025; 15:1480293. [PMID: 40357398 PMCID: PMC12066693 DOI: 10.3389/fcimb.2025.1480293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 03/31/2025] [Indexed: 05/15/2025] Open
Abstract
Introduction Sarcopenia, an age-related disorder marked by decreased skeletal muscle mass, strength, and function, is associated with negative health impacts in individuals and financial burdens on families and society. Studies have suggested that age-related alterations in gut microbiota may contribute to the development of sarcopenia in older people through the gut-muscle axis, thus modulation of gut microbiota may be a promising approach for sarcopenia treatment. However, the characteristic gut microbiota for sarcopenia has not been consistent across studies. Therefore, the aim of this study was to compare the diversity and compositional differences in the gut microbiota of older people with and without sarcopenia, and to identify gut microbiota biomarkers with therapeutic potential for sarcopenia. Methods The PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Database were searched studies about the gut microbiota characteristics in older people with sarcopenia. The quality of included articles was assessed by the Newcastle-Ottawa Scale (NOS). Weighted standardized mean differences (SMDs) and 95% confidence intervals (CIs) for α-diversity index were estimated using a random effects model. Qualitative synthesis was conducted for β-diversity and the correlation between gut microbiota and muscle parameters. The relative abundance of the gut microbiota was analyzed quantitatively and qualitatively, respectively. Results Pooled estimates showed that α-diversity was significantly lower in older people with sarcopenia (SMD: -0.41, 95% CI: -0.57 to -0.26, I²: 71%, P < 0.00001). The findings of β-diversity varied across included studies. In addition, our study identified gut microbiota showing a potential and negative correlation with sarcopenia, such as Prevotella, Slackia, Agathobacter, Alloprevotella, Prevotella copri, Prevotellaceae sp., Bacteroides coprophilus, Mitsuokella multacida, Bacteroides massiliensis, Bacteroides coprocola Conversely, a potential and positive correlation was observed with opportunistic pathogens like Escherichia-Shigella, Eggerthella, Eggerthella lenta and Collinsella aerofaciens. Discussion This study showed that α-diversity is decreased in sarcopenia, probably predominantly due to diminished richness rather than evenness. In addition, although findings of β-diversity varied across included studies, the overall trend toward a decrease in SCFAs-producing bacteria and an increase in conditionally pathogenic bacteria. This study provides new ideas for targeting the gut microbiota for the prevention and treatment of sarcopenia. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD42024573090, identifier CRD42024573090.
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Affiliation(s)
- Yanqing Ren
- Department of Rehabilitation, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, China
- Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China
| | - Xiangfeng He
- Department of Rehabilitation, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Ling Wang
- Department of Rehabilitation, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, China
- Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China
| | - Nan Chen
- Department of Rehabilitation, Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, China
- Department of Rehabilitation, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
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Yu Z, Wang Y, Guo Y, Zhu R, Fang Y, Yao Q, Fu H, Zhou A, Ma L, Shou Q. Exploring the Therapeutic and Gut Microbiota-Modulating Effects of Qingreliangxuefang on IMQ-Induced Psoriasis. Drug Des Devel Ther 2025; 19:3269-3291. [PMID: 40322026 PMCID: PMC12048299 DOI: 10.2147/dddt.s492044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 03/24/2025] [Indexed: 05/08/2025] Open
Abstract
Purpose To investigate the therapeutic and gut microbiota-modulating effects of Qingreliangxuefang (QRLXF) on psoriasis. Materials and Methods We used network pharmacology, a computational approach, to identify key bioactive compounds and biological targets, and explored the molecular mechanisms of QRLXF. The effects of QRLXF on keratinocyte proliferation and inflammation were evaluated using a mouse model of psoriasis. Changes in the gut microbiota were analyzed via 16SrDNA sequencing, and T cell subsets were assessed using flow cytometry. Results Network pharmacology analysis suggested that QRLXF ameliorated psoriasis by modulating Th17 cell differentiation. Further experiments confirmed the anti-inflammatory effects and relief of psoriatic lesions in IMQ-induced mice. 16SrDNA sequencing revealed significant shifts in the gut microbiota, notably increases in Ligilactobacillus and Lactobacillus genera and decreases in Anaerotruncus, Negativibacillus, Bilophila, and Mucispirillum, suggesting a potential relationship between specific microbiota changes and Th17 cell differentiation. Conclusion QRLXF alleviated psoriatic dermatitis by regulating Th17 cell responses and modifying gut microbiota profiles, highlighting its therapeutic potential for psoriasis treatment.
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Affiliation(s)
- Zhengyao Yu
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Yongkang Hospital of Traditional Chinese Medicine, Jinhua, Zhejiang, 321300, People’s Republic of China
| | - Yingying Wang
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Yingxue Guo
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Ruotong Zhu
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China
- The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Yimiao Fang
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China
| | - Qinghua Yao
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Xinhua Hospital of Zhejiang Province, Hangzhou, Zhejiang, 310005, People’s Republic of China
| | - Huiying Fu
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Yongkang Hospital of Traditional Chinese Medicine, Jinhua, Zhejiang, 321300, People’s Republic of China
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Ang Zhou
- Department of Dermatology, Yiwu Central Hospital Medical Community Choujiang Hospital District, Yiwu, Zhejiang, 322000, People’s Republic of China
| | - Lili Ma
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China
| | - Qiyang Shou
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Jinhua Academy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
- Yongkang Hospital of Traditional Chinese Medicine, Jinhua, Zhejiang, 321300, People’s Republic of China
- School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
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Xu Q, Lv Y, Yuan X, Huang G, Guo Z, Tan J, Qiu S, Wang X, Wei C. Simulated Gastrointestinal Digestion and In Vitro Fecal Fermentation of Purified Pyracantha fortuneana (Maxim.) Li Fruit Pectin. Foods 2025; 14:1529. [PMID: 40361612 PMCID: PMC12071275 DOI: 10.3390/foods14091529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Revised: 04/15/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025] Open
Abstract
Pyracantha fortuneana, an underutilized wild plant, has been found to have a high nutritional value. This study used simulated digestion and fecal fermentation models to investigate the digestive properties of the purified acidic pectin polysaccharide of Pyracantha fortuneana and its impact on the gut microbiota and metabolites. Pyracantha fortuneana polysaccharide (PFP) is mainly composed of rhamnose (Rha), galacturonic acid (GalA), glucose (Glc), galactose (Gal), and arabinose (Ara), with a molecular weight (Mw) of 851.25 kDa. Following simulated digestion, the Mw of PFP remained consistent. The reduced sugar content showed minimal change, suggesting that PFP exhibits resistance to gastrointestinal digestion and can effectively reach the colon. Following fecal fermentation, the molecular weight, monosaccharide, and carbohydrate contents of PFP decreased, while the short-chain fatty acid content increased. This suggests that PFP is susceptible to degradation by microorganisms and can be metabolized into acetic acid and n-butyric acid, contributing to the regulation of intestinal health. Meanwhile, PFP promotes the reproduction of beneficial bacteria such as Bacteroides, Dialister, and Dysgonomonas, inhibits the growth of harmful bacteria like Proteus, and generates metabolites such as thiamine, leonuriside A, oxoadipic acid, S-hydroxymethylglutathione, and isonicotinic acid, which exert beneficial effects on human health. These results indicate that PFP has great potential in regulating the gut microbiota and generating beneficial metabolites to promote intestinal functional health and can be used as a prebiotic to prevent diseases by improving intestinal health.
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Affiliation(s)
- Qingrui Xu
- Key Laboratory of Fermentation Engineering and Biological Pharmacy of Guizhou Province, School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China
| | - Yiyi Lv
- Key Laboratory of Fermentation Engineering and Biological Pharmacy of Guizhou Province, School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China
| | - Xiaohui Yuan
- Key Laboratory of Fermentation Engineering and Biological Pharmacy of Guizhou Province, School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China
| | - Guichun Huang
- Key Laboratory of Fermentation Engineering and Biological Pharmacy of Guizhou Province, School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China
- Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Institute of Agro-Bioengineering, College of Life Sciences, Guizhou University, Guiyang 550025, China
| | - Zhongxia Guo
- Key Laboratory of Fermentation Engineering and Biological Pharmacy of Guizhou Province, School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China
| | - Jiana Tan
- Key Laboratory of Fermentation Engineering and Biological Pharmacy of Guizhou Province, School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China
| | - Shuyi Qiu
- Key Laboratory of Fermentation Engineering and Biological Pharmacy of Guizhou Province, School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China
| | - Xiaodan Wang
- Key Laboratory of Fermentation Engineering and Biological Pharmacy of Guizhou Province, School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China
| | - Chaoyang Wei
- Key Laboratory of Fermentation Engineering and Biological Pharmacy of Guizhou Province, School of Liquor and Food Engineering, Guizhou University, Guiyang 550025, China
- Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Institute of Agro-Bioengineering, College of Life Sciences, Guizhou University, Guiyang 550025, China
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Shi J, Zhuang T, Li W, Wu X, Wang J, Lyu R, Chen J, Liu C. Effects of Time-Restricted Fasting-Nicotinamide Mononucleotide Combination on Exercise Capacity via Mitochondrial Activation and Gut Microbiota Modulation. Nutrients 2025; 17:1467. [PMID: 40362776 PMCID: PMC12073279 DOI: 10.3390/nu17091467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2025] [Revised: 04/17/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND/OBJECTIVES Athletic performance matters for athletes and fitness enthusiasts. Scientific dietary intervention may boost athletic performance alongside training. Intermittent fasting, like time-restricted fasting (TF), may enhance metabolic health. NAD+ supplement nicotinamide mononucleotide (NMN) improves mitochondrial activity. Both potentially boost athletic performance. However, whether TF combined with NMN treatment can further enhance athletic ability is unclear. METHODS Healthy Kunming mice were utilized to test the effects of NMN and TF on the athletic performance of mice. To simulate the in vivo state and further verify the role of TF and NMN, low glucose combined with NMN was used to intervene in C2C12 cells. The exercise capacity of mice was evaluated through motor behavior experiments. At the same time, blood gas analysis and kit tests were used to assess oxygen uptake capacity and post-exercise oxidative stress levels. Muscle development and mitochondrial function were examined through gene expression, protein analysis, and enzyme activity tests, and the distribution of intestinal microbiota and short-chain fatty acid content were also analyzed. RESULTS The results show that TF combined with NMN improved mitochondrial dynamics and biosynthesis, mitochondrial respiratory function, and oxidative metabolism. Then, the intervention enhanced mice's endurance, limb strength, motor coordination, and balance and reduced oxidative damage after exercise. Moreover, TF combined with NMN significantly increased the gut microbiota diversity and upregulated Ruminococcus, Roseburia, and Akkermansia in intestinal bacteria and short-chain fatty acids, which are associated with athletic performance. CONCLUSION TF combined with NMN enhanced mitochondrial function, improved energy metabolism, modulated the gut microbiota and short-chain fatty acids, and affected muscle fiber transformation, ultimately leading to an overall improvement in exercise performance. These findings provide a theoretical framework for expanding the application of NMN and TF in kinesiology.
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Affiliation(s)
- Jian Shi
- College of Food Science, South China Agricultural University, Guangzhou 510642, China; (J.S.); (W.L.); (X.W.); (J.W.); (R.L.); (J.C.)
- Guangdong Provincial Key Laboratory of Food Quality and Safety, Guangzhou 510642, China
| | - Tingting Zhuang
- College of Agricultural Engineering, Guangdong Meizhou Vocational and Technical College, Meizhou 514028, China;
| | - Weiye Li
- College of Food Science, South China Agricultural University, Guangzhou 510642, China; (J.S.); (W.L.); (X.W.); (J.W.); (R.L.); (J.C.)
- Guangdong Provincial Key Laboratory of Food Quality and Safety, Guangzhou 510642, China
| | - Xueping Wu
- College of Food Science, South China Agricultural University, Guangzhou 510642, China; (J.S.); (W.L.); (X.W.); (J.W.); (R.L.); (J.C.)
- Guangdong Provincial Key Laboratory of Food Quality and Safety, Guangzhou 510642, China
| | - Junming Wang
- College of Food Science, South China Agricultural University, Guangzhou 510642, China; (J.S.); (W.L.); (X.W.); (J.W.); (R.L.); (J.C.)
- Guangdong Provincial Key Laboratory of Food Quality and Safety, Guangzhou 510642, China
| | - Ruiying Lyu
- College of Food Science, South China Agricultural University, Guangzhou 510642, China; (J.S.); (W.L.); (X.W.); (J.W.); (R.L.); (J.C.)
- Guangdong Provincial Key Laboratory of Food Quality and Safety, Guangzhou 510642, China
| | - Jingxin Chen
- College of Food Science, South China Agricultural University, Guangzhou 510642, China; (J.S.); (W.L.); (X.W.); (J.W.); (R.L.); (J.C.)
- Guangdong Provincial Key Laboratory of Food Quality and Safety, Guangzhou 510642, China
| | - Chunhong Liu
- College of Food Science, South China Agricultural University, Guangzhou 510642, China; (J.S.); (W.L.); (X.W.); (J.W.); (R.L.); (J.C.)
- Guangdong Provincial Key Laboratory of Food Quality and Safety, Guangzhou 510642, China
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Yokota H, Tanaka Y, Ohno H. Coculture of Bifidobacterium bifidum G9-1 With Butyrate-Producing Bacteria Promotes Butyrate Production. Microbiol Immunol 2025. [PMID: 40269463 DOI: 10.1111/1348-0421.13224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 04/13/2025] [Accepted: 04/15/2025] [Indexed: 04/25/2025]
Abstract
Supplementation with Bifidobacterium bifidum G9-1 (BBG9-1) has been established to enhance the production of butyrate, a short-chain fatty acid (SCFA) known for its beneficial effects in alleviating constipation. We hypothesized that BBG9-1 alters gut microbiota such that bacteria that produce butyric acid from lactate and acetate become more abundant. In this study, we sought to determine whether BBG9-1 promotes the growth of butyrate-producing bacteria and thereby enhances butyrate production. BBG9-1 was cocultured with different butyrate-producing bacteria to compare differences in the SCFA production of cocultures and monocultures. We indeed detected significant increases in the production of SCFAs in cocultures compared to monocultures. Moreover, lactate and butyrate production increased in a time-dependent manner in the BBG9-1 and Faecalibacterium prausnitzii ID 6052 coculture. In addition, acetate production in cocultures initially increased until 16 h, followed by a decline between 20 and 24 h, and a subsequent significant increase at 48 h. Comparatively, lactate and acetate production in the BBG9-1 and Anaerostipes caccae JCM 13470T coculture peaked at 16 h and declined thereafter, and butyrate production increased in a time-dependent manner. In contrast, lactate, acetate, and butyrate production in the BBG9-1 and Roseburia hominis JCM 17582T coculture increased in a time-dependent manner. These findings indicate that butyrate-producing bacteria increase butyrate production by utilizing BBG9-1-produced lactate and acetate. Thus, the butyrate-mediated physiological activity of BBG9-1 could be attributed to an indirect enhancement of butyrate production.
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41
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Martin D, Bonneau M, Orfila L, Horeau M, Hazon M, Demay R, Lecommandeur E, Boumpoutou R, Guillotel A, Guillemot P, Croyal M, Cressard P, Cressard C, Cuzol A, Monbet V, Derbré F. Atypical gut microbial ecosystem from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen store in mice. Cell Rep 2025; 44:115448. [PMID: 40154488 DOI: 10.1016/j.celrep.2025.115448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 01/13/2025] [Accepted: 02/28/2025] [Indexed: 04/01/2025] Open
Abstract
Although the gut microbiota is known to act as a bridge between dietary nutrients and the body's energy needs, the interactions between the gut microbiota, host energy metabolism, and exercise capacity remain uncertain. Here, we characterized the gut microbiota ecosystem in a cohort of healthy normo-weight humans with highly heterogeneous aerobic exercise capacities and closely related body composition and food habits. While our data support the idea that the bacterial ecosystem appears to be modestly altered between individuals with low-to-high exercise capacities and close food habits, we report that gut bacterial α diversity, density, and functional richness are significantly reduced in athletes with very high exercise capacity. By using fecal microbiota transplantation, we report that the engraftment of gut microbiota from athletes with very high exercise capacity improves insulin sensitivity and muscle glycogen stores into transplanted mice, which highlights promising therapeutic perspectives in fecal transplantation from human donors selected based on exercise capacity traits.
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Affiliation(s)
- David Martin
- Laboratory "Movement Sport and Health Sciences", University of Rennes 2/ENS Rennes, Rennes, France; IRMAR - UMR CNRS 6625, University of Rennes, Rennes, France
| | - Mathis Bonneau
- Laboratory "Movement Sport and Health Sciences", University of Rennes 2/ENS Rennes, Rennes, France
| | - Luz Orfila
- Laboratory "Movement Sport and Health Sciences", University of Rennes 2/ENS Rennes, Rennes, France
| | - Mathieu Horeau
- Laboratory "Movement Sport and Health Sciences", University of Rennes 2/ENS Rennes, Rennes, France
| | | | - Romain Demay
- Laboratory "Movement Sport and Health Sciences", University of Rennes 2/ENS Rennes, Rennes, France
| | | | - Rufin Boumpoutou
- Laboratory "Movement Sport and Health Sciences", University of Rennes 2/ENS Rennes, Rennes, France; Rennes Ortho Sport, Polyclinique Saint Laurent, Rennes, France
| | - Arthur Guillotel
- Laboratory "Movement Sport and Health Sciences", University of Rennes 2/ENS Rennes, Rennes, France; Stade Rennais Football Club, Rennes, France
| | | | - Mikael Croyal
- Institut du thorax, Nantes Université, CNRS, INSERM, Nantes, France; UMS 016, UMS 3556, Nantes Université, INSERM, CNRS, Nantes, France
| | | | | | - Anne Cuzol
- IUT Vannes, University of South Brittany, Vannes, France
| | - Valérie Monbet
- IRMAR - UMR CNRS 6625, University of Rennes, Rennes, France.
| | - Frédéric Derbré
- Laboratory "Movement Sport and Health Sciences", University of Rennes 2/ENS Rennes, Rennes, France.
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Gao D, Zhuang Y, Liu S, Ma B, Xu Y, Zhang H, Nuermaimaiti Y, Chen T, Hou G, Guo W, You J, Huang Z, Xiao J, Wang W, Li M, Li S, Cao Z. Multi-omics profiling of dairy cattle oxidative stress identifies hindgut-derived Phascolarctobacterium succinatutens exhibiting antioxidant activity. NPJ Biofilms Microbiomes 2025; 11:61. [PMID: 40263287 PMCID: PMC12015594 DOI: 10.1038/s41522-025-00698-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Accepted: 04/07/2025] [Indexed: 04/24/2025] Open
Abstract
An imbalance between oxidative and antioxidant processes in the host can lead to excessive oxidation, a condition known as oxidative stress (OS). Although changes in the hindgut microbiota have been frequently linked to OS, the specific microbial and metabolic underpinnings of this association remain unclear. In this study, we enrolled 81 postpartum Holstein cows and stratified them into high oxidative stress (HOS, n = 9) and low oxidative stress (LOS, n = 9) groups based on the oxidative stress index (OSi). Using a multi-omics approach, we performed 16S rRNA gene sequencing to evaluate microbial diversity, conducted metagenomic analysis to identify functional bacteria, and utilized untargeted metabolomics to profile serum metabolites. Our analyses revealed elevated levels of kynurenine, formyl-5-hydroxykynurenamine, and 5-hydroxyindole-3-acetic acid in LOS dairy cows. Additionally, the LOS cows had a higher abundance of short-chain fatty acids (SCFAs)-producing bacteria, including Bacteroidetes bacterium, Paludibacter propionicigenes, and Phascolarctobacterium succinatutens (P. succinatutens), which were negatively correlated with OSi. To explore the potential role of these bacteria in mitigating OS, we administered P. succinatutens (108 cfu/day for 14 days) to C57BL/6 J mice (n = 10). Oral administration of P. succinatutens significantly increased serum total antioxidant capacity, decreased total oxidants, and reduced OSi in mice. Moreover, this treatment promoted activation of the Nrf2-Keap1 antioxidant pathway, significantly enhancing the enzymatic activities of GSH-Px and SOD, as well as the concentrations of acetate and propionate in the colon. In conclusion, our findings suggest that systemic tryptophan metabolism and disordered SCFAs production are concurrent factors influenced by hindgut microbiota and associated with OS development. Modulating the hindgut microbiota, particularly by introducing specific SCFAs-producing bacteria, could be a promising strategy for combating OS.
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Affiliation(s)
- Duo Gao
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Yimin Zhuang
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shuai Liu
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Boyan Ma
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Yiming Xu
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Hongxing Zhang
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Yiliyaer Nuermaimaiti
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Tianyu Chen
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Guobin Hou
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Wenli Guo
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Jingtao You
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Zhiyu Huang
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Jianxin Xiao
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China
| | - Wei Wang
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Mengmeng Li
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shengli Li
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Zhijun Cao
- State Key Laboratory of Animal Nutrition and Feeding, International Calf and Heifer Organization, College of Animal Science and Technology, China Agricultural University, Beijing, China.
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Schell LD, Chadaideh KS, Allen-Blevins CR, Venable EM, Carmody RN. Dietary preservatives alter the gut microbiota in vitro and in vivo with sex-specific consequences for host metabolic development in a mouse model. Am J Clin Nutr 2025:S0002-9165(25)00196-0. [PMID: 40250761 DOI: 10.1016/j.ajcnut.2025.04.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 03/14/2025] [Accepted: 04/06/2025] [Indexed: 04/20/2025] Open
Abstract
BACKGROUND Antibiotics in early life can promote adiposity via interactions with the gut microbiota, but they represent only one possible route of antimicrobial exposure. Dietary preservatives exhibit antimicrobial activity, contain chemical structures accessible to microbial enzymes, and may therefore similarly disrupt microbial contributions to metabolic development. OBJECTIVES Here, we test the hypothesis that preservatives alter the gut microbiota with consequences for host metabolism. METHODS We screened common dietary preservatives for in vitro and ex vivo activity against a panel of gut bacteria and whole fecal microbial communities, profiling outcomes via optical density measurements and 16S rDNA sequencing. We then exposed adult mice to diet-relevant doses of 4 preservatives [acetic acid, butylated hydroxyanisole (BHA), ethylenediaminetetraacetic acid (EDTA), and sodium sulfite] or ampicillin (positive control) for 7 d. Finally, we examined the effects of early-life EDTA and low-dose ampicillin exposure starting in gestation in a mouse model, tracking differences in growth and metabolism. RESULTS Preservatives altered microbial growth and community structure in vitro, ex vivo, and in vivo, but with compound-specific changes in gut microbiota composition distinct from those of ampicillin. Long-term EDTA exposure from gestation reduced calorie absorption and cecal acetate, resulting in 32% lower gains in body fat in females for a given food intake (±12% standard error, linear mixed effects model). Females exposed to ampicillin exhibited a similar 42% (±11%) reduction in food-adjusted gains in adiposity, along with larger brains and smaller livers. By contrast, among males, EDTA had no detectable metabolic impacts whereas ampicillin exposure increased food-adjusted gain in body fat by 108% (±12%). CONCLUSIONS Our results highlight the potential for everyday doses of common preservatives to affect the gut microbiota and impact metabolism differently in males and females. Thus, despite their generally regarded as safe designation, preservatives could have unintended consequences for consumer health via their impact on the gut microbiota.
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Affiliation(s)
- Laura D Schell
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, United States.
| | - Katia S Chadaideh
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, United States
| | - Cary R Allen-Blevins
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, United States
| | - Emily M Venable
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, United States
| | - Rachel N Carmody
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, United States.
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Atzeni A, Hernández-Cacho A, Khoury N, Babio N, Belzer C, Vioque J, Corella D, Fitó M, Clish C, Vidal J, Konstanti P, Gonzales-Palacios S, Coltell O, Goday A, Moreno Indias I, Carlos Chillerón S, Ruiz-Canela M, Tinahones FJ, Hu FB, Salas-Salvadó J. The link between ultra-processed food consumption, fecal microbiota, and metabolomic profiles in older mediterranean adults at high cardiovascular risk. Nutr J 2025; 24:62. [PMID: 40247349 PMCID: PMC12007308 DOI: 10.1186/s12937-025-01125-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Accepted: 04/02/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Ultra-processed food (UPF) consumption has been linked to adverse metabolic outcomes, potentially mediated by alterations in gut microbiota and metabolite production. OBJECTIVE This study aims to explore the cross-sectional and longitudinal associations between NOVA-classified UPF consumption, fecal microbiota, and fecal metabolome in a population of Mediterranean older adults at high cardiovascular risk. METHODS A total of 385 individuals, aged between 55 and 75 years, were included in the study. Dietary and lifestyle information, anthropometric measurements, and stool samples were collected at baseline and after 1-year follow-up. Fecal microbiota and metabolome were assessed using 16 S rRNA sequencing and liquid chromatography-tandem mass spectrometry, respectively. RESULTS At baseline, higher UPF consumption was associated with lower abundance of Ruminococcaceae incertae sedis (β = - 0.275, P = 0.047) and lower concentrations of the metabolites propionylcarnitine (β = - 0.0003, P = 0.013) and pipecolic acid (β = - 0.0003, P = 0.040) in feces. Longitudinally, increased UPF consumption was linked to reduced abundance of Parabacteroides spp. after a 1-year follow-up (β = - 0.278, P = 0.002). CONCLUSIONS High UPF consumption was associated with less favorable gut microbiota and metabolite profiles, suggesting a possible link to reduced short-chain fatty acid (SCFA) production, altered mitochondrial energy metabolism, and impaired amino acid metabolism. These findings support the reduction of UPF consumption and the promotion of dietary patterns rich in fiber for better gut health. Further research is needed to confirm these associations and clarify the underlying mechanisms. TRIAL REGISTRATION ISRCTN89898870 ( https://doi.org/10.1186/ISRCTN89898870 ).
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Affiliation(s)
- Alessandro Atzeni
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
- Desenvolupament i Salut Mental (ANUT-DSM) Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Alimentació, Nutrició, Universitat Rovira i Virgili, Reus, Spain.
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain.
| | - Adrián Hernández-Cacho
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Desenvolupament i Salut Mental (ANUT-DSM) Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Alimentació, Nutrició, Universitat Rovira i Virgili, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - Nadine Khoury
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Desenvolupament i Salut Mental (ANUT-DSM) Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Alimentació, Nutrició, Universitat Rovira i Virgili, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - Nancy Babio
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Desenvolupament i Salut Mental (ANUT-DSM) Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Alimentació, Nutrició, Universitat Rovira i Virgili, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands
| | - Jesús Vioque
- CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernández (ISABIAL-UMH), Alicante, Spain
| | - Dolores Corella
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine, University of Valencia, Valencia, Spain
| | - Montserrat Fitó
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar de Investigaciones Médicas Municipal d'Investigació Médica (IMIM), Barcelona, Spain
| | - Clary Clish
- Metabolomics Platform, The Broad Institute of MIT and Harvard, Boston, MA, USA
| | - Josep Vidal
- CIBER Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Endocrinology, Institut d'Investigacions Biomédiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Prokopis Konstanti
- Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands
| | - Sandra Gonzales-Palacios
- CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria y Biomédica de Alicante, Universidad Miguel Hernández (ISABIAL-UMH), Alicante, Spain
| | - Oscar Coltell
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Department of Computer Languages and Systems, Universitat Jaume I, Castellón, Spain
| | - Albert Goday
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar de Investigaciones Médicas Municipal d'Investigació Médica (IMIM), Barcelona, Spain
- Departament de Medicina, Universitat Autónoma de Barcelona, Barcelona, Spain
| | - Isabel Moreno Indias
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Silvia Carlos Chillerón
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain
- Epidemiología y Salud Pública, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Miguel Ruiz-Canela
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain
- Epidemiología y Salud Pública, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Francisco J Tinahones
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Frank B Hu
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA
- Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jordi Salas-Salvadó
- Centro de Investigación Biomédica en Red - Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.
- Desenvolupament i Salut Mental (ANUT-DSM) Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Alimentació, Nutrició, Universitat Rovira i Virgili, Reus, Spain.
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain.
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Wang XM, Huang HJ, Sun XW, Wei RQ, Chen HY, Liu C, Liu SJ. Identification and Characterization of Two Novel Members of the Family Eubacteriaceae, Anaerofustis butyriciformans sp. nov. and Pseudoramibacter faecis sp. nov., Isolated from Human Feces. Microorganisms 2025; 13:916. [PMID: 40284751 PMCID: PMC12029686 DOI: 10.3390/microorganisms13040916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 04/11/2025] [Accepted: 04/14/2025] [Indexed: 04/29/2025] Open
Abstract
Members of Eubacteriaceae are involved in host health and diseases. Two Gram-stain-positive, strictly anaerobic, non-motile, non-spore-forming, and rod-shaped bacterial strains, HA2171T and HA2172T, were isolated from the feces of Chinese healthy donors. Based on 16S rRNA gene sequences, HA2171T and HA2172T belonged to the family Eubacteriaceae. Physiological and biochemical characterizations indicated that HA2171T and HA2172T were neutrophilic, mesophilic, and tolerant to low-concentration NaCl. The major cellular fatty acids (>10.0%) of HA2171T were C16:0, C14:0, C18:1ω7c, and C17:0 2-OH, and those of HA2172T were C14:0 and C16:0. MK-6 was the respiratory quinone in both strains. Phylogenetic and phylogenomic analyses showed that HA2171T was closest to Anaerofustis stercorihominis ATCC BAA-858T and that HA2172T as closest to Pseudoramibacter alactolyticus ATCC 23263T. Genome annotation revealed that the HA2171T and HA2172T were able to metabolize carbohydrates and produce acetate and butyrate. HA2172T contains genes associated with hydrogen sulfide production, which is a potential risk for diseases. Based on the phylogenetic, phenotypic, and chemotaxonomic characteristics, we propose that HA2171T and HA2172T represent two novel species, and the names Anaerofustis butyriciformans sp. nov. and Pseudoramibacter faecis sp. nov. are proposed.
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Affiliation(s)
- Xiao-Meng Wang
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; (X.-M.W.); (H.-J.H.); (X.-W.S.); (R.-Q.W.); (H.-Y.C.)
| | - Hao-Jie Huang
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; (X.-M.W.); (H.-J.H.); (X.-W.S.); (R.-Q.W.); (H.-Y.C.)
| | - Xin-Wei Sun
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; (X.-M.W.); (H.-J.H.); (X.-W.S.); (R.-Q.W.); (H.-Y.C.)
| | - Rui-Qi Wei
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; (X.-M.W.); (H.-J.H.); (X.-W.S.); (R.-Q.W.); (H.-Y.C.)
| | - Hao-Yu Chen
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; (X.-M.W.); (H.-J.H.); (X.-W.S.); (R.-Q.W.); (H.-Y.C.)
| | - Chang Liu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; (X.-M.W.); (H.-J.H.); (X.-W.S.); (R.-Q.W.); (H.-Y.C.)
| | - Shuang-Jiang Liu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; (X.-M.W.); (H.-J.H.); (X.-W.S.); (R.-Q.W.); (H.-Y.C.)
- State Key Laboratory of Microbial Resources, Environmental Microbiology Research Center (EMRC), Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
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Xue M, Xu P, Wen H, He J, Chen J, Kong C, Li X, Wang H, Guo X, Su Y, Li H, Song C. Gut Microbe Rikenellaceae_RC9_gut_group and Knoellia-Mediated Acetic Acid Regulates Glucose and Lipid Metabolism in the Muscle of Freshwater Drum ( Aplodinotus grunniens) Under High-Fat Diets. AQUACULTURE NUTRITION 2025; 2025:9667909. [PMID: 40271481 PMCID: PMC12017940 DOI: 10.1155/anu/9667909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 03/10/2025] [Indexed: 04/25/2025]
Abstract
Metabolic disorders and complications induced by high-fat diets (HFDs) are a hot research topic in aquatic animal nutrition and health, but the mechanism of gut microbes and their metabolites on muscle homeostasis is not yet clear. In this study, a 16-week HFD (Con, 6% fat and HFD, 12% fat) rearing experiment was conducted with a freshwater drum (20.88 ± 2.75 g, about 20,000 fish per pond) to investigate the underlying regulation of gut microbes on muscle nutrient and metabolism. Results revealed that HFD had no remarkable effect on proximate nutrients (moisture, ash, crude protein, and crude fat), total amino acids, and fatty acids contents in muscle. Moreover, decreased acetic acid content by HFD in the gut and muscle was confirmed to regulate lipid metabolism, as evidenced by the activation of fatty acid synthesis (acetyl-CoA carboxylase alpha [ACC1] and sterol regulatory element binding protein-1 [SREBP1]) and inhibition of fatty acid lipolysis (AMP-activated protein kinase [AMPK], adipose triglyceride lipase [ATGL], and carnitine palmitoyl transferase 2 [CPT2]). Interestingly, RNA-seq revealed glycolytic metabolism (glycolysis/gluconeogenesis and pyruvate metabolism) was active in the muscle under HFD, which was further confirmed to be the intermediate for acetic acid to regulate lipid metabolism. Strikingly, gut microbe Rikenellaceae_RC9_gut_group and Knoellia regulate muscle lipid and glucose metabolism through their derived metabolite acetic acid, which is the key target for gut microbe to regulate muscle. Taken together, these results reveal the regulatory mechanism of gut microbes and derived metabolites on muscle metabolism and development, providing a theoretical basis for the healthy regulation of HFD in aquatic animals.
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Affiliation(s)
- Miaomiao Xue
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
| | - Pao Xu
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Haibo Wen
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Jiyan He
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Jianxiang Chen
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Changxin Kong
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
| | - Xiaowei Li
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
| | - Hang Wang
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
| | - Xinxin Guo
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
| | - Yi Su
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
| | - Hongxia Li
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
| | - Changyou Song
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China
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Ur Rahman Shah SA, Hao Y, Tang B, Ahmad M, He D, Nabi G, Zheng J, Wan X, Wang C, Wang K. The association of seasonal dietary shift with fecal metabolome and microbiota in the captive Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis). ENVIRONMENTAL RESEARCH 2025; 271:121082. [PMID: 39929417 DOI: 10.1016/j.envres.2025.121082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 02/06/2025] [Accepted: 02/07/2025] [Indexed: 02/18/2025]
Abstract
The gut microbiota can act as a buffer against changes in energy and food availability and adapt plastically to fluctuations in the host's diet. However, it is unknown how changes in the gut microbiome with the seasons impact microbial metabolism and the accessibility of nutrients to hosts. The study utilized 16S rRNA and UHPLC-MS/MS approaches to examine seasonal fecal metabolome variations in the captive Yangtze finless porpoises (YFPs) to determine if these variations are linked to nutrient intake or gut microbiome composition changes. The YFPs were mostly fed a frozen and live fish diet, with different food intakes yearly. We found that gut microbial diversity remained constant, but community structure varied seasonally. Firmicutes and Cyanobacteria were higher in winter, Actinobacteria in spring and fall, and proteobacteria in summer. The genus Paeniclostridium was significantly higher in the spring season, Romboutsia and Clostridium_sensu_stricto_13 were significantly higher in the summer, while Terrisporobacter and Macrococcus were significantly higher in the fall group. The study reported that seasonal dietary variation significantly impacted the fecal metabolome by affecting the metabolism, including energy, amino acid, carbohydrate, and nucleotide metabolism of the captive YFP. Moreover, significant correlations between metabolome and microbiome were found, and these correlations may indicate that the captive YFP has adapted to cope with dietary variations and enhance energy acquisition. These findings improve our knowledge of the link between microbiota, diet, metabolites, and the physiology of the host and suggest that gut microbial populations may adapt continuously to changes in diet.
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Affiliation(s)
- Syed Ata Ur Rahman Shah
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; University of Chinese Academy of Sciences, Beijing, China
| | - Yujiang Hao
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China.
| | - Bin Tang
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; University of Chinese Academy of Sciences, Beijing, China; National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China
| | - Maaz Ahmad
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; University of Chinese Academy of Sciences, Beijing, China
| | - Dekui He
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China
| | - Ghulam Nabi
- Department of Zoology, Institute of Molecular Biology and Biotechnology, University of Lahore, Pakistan
| | - Jinsong Zheng
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China
| | - Xiaoling Wan
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China
| | - Chaoqun Wang
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China
| | - Kexiong Wang
- Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; National Aquatic Biological Resource Center, NABRC, Wuhan, 430072, China
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MacCann R, Li J, Leon AAG, Negi R, Alalwan D, Tinago W, McGettrick P, Cotter AG, Landay A, Sabin C, O’Toole PW, Mallon PWG. Associations Between the Gut Microbiome, Inflammation, and Cardiovascular Profiles in People With Human Immunodeficiency Virus. J Infect Dis 2025; 231:e781-e791. [PMID: 39854172 PMCID: PMC11998580 DOI: 10.1093/infdis/jiaf043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/08/2025] [Accepted: 01/23/2025] [Indexed: 01/26/2025] Open
Abstract
BACKGROUND Inflammation and innate immune activation are associated with chronic human immunodeficiency virus (HIV) infection, despite effective treatment. Although gut microbiota alterations are linked to systemic inflammation, their relationship with HIV infection the relationships between the gut microbiome, inflammation, and HIV remains unclear. METHODS The HIV UPBEAT Coronary Artery Disease sub-study evaluated cardiovascular disease (CVD) in people with and without HIV. Subclinical CVD was assessed using coronary computed tomography angiography (CCTA). Thirty-four biomarkers were measured using quantitative immunoassays. Stool samples underwent 16S rRNA sequencing. Differentially abundant species were identified by analysis of compositions of microbiomes with bias correction (ANCOM-BC) and correlated to biomarkers, diet, and CCTA outcomes using Spearman correlation. RESULTS Among 81 participants (median age, 51 years; 73% male), people with HIV (n = 44) had higher rates of hypercholesterolemia (P < .025). Gut microbiome β-diversity differed significantly by HIV status. Enriched Bifidobacterium pseudocatenulatum, Megamonas hypermegale, and Selenomonas ruminantium correlated with lower plaque burden, while depleted Ruminococcus bromii correlated with higher plaque burden and fat intake. Depleted Bacteroides spp and Alistepes spp correlated with elevated biomarkers (D-dimer, CD40 ligand, C-reactive protein, and interferon-γ). CONCLUSIONS Gut microbiota differences in people with HIV were linked to subclinical CVD, diet, and inflammation, highlighting the microbiome's role in cardiovascular risk in HIV infection.
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Affiliation(s)
- Rachel MacCann
- School of Medicine, University College Dublin
- Department of Infectious Diseases, St Vincent's University Hospital
- Centre for Experimental Pathogen Host Research, University College Dublin
| | - Junhui Li
- School of Microbiology and APC Microbiome Ireland, University College Cork
| | | | - Riya Negi
- Centre for Experimental Pathogen Host Research, University College Dublin
| | - Dana Alalwan
- Centre for Experimental Pathogen Host Research, University College Dublin
| | - Willard Tinago
- Centre for Experimental Pathogen Host Research, University College Dublin
| | - Padraig McGettrick
- School of Medicine, University College Dublin
- Centre for Experimental Pathogen Host Research, University College Dublin
- Department of Infectious Diseases, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Aoife G Cotter
- Centre for Experimental Pathogen Host Research, University College Dublin
- Department of Infectious Diseases, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Alan Landay
- Department of Internal Medicine, University of Texas Medical Branch, Galveston
| | - Caroline Sabin
- Institute for Global Health, University College London, United Kingdom
| | - Paul W O’Toole
- School of Microbiology and APC Microbiome Ireland, University College Cork
| | - Patrick W G Mallon
- School of Medicine, University College Dublin
- Department of Infectious Diseases, St Vincent's University Hospital
- Centre for Experimental Pathogen Host Research, University College Dublin
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Corbin KD, Igudesman D, Smith SR, Zengler K, Krajmalnik-Brown R. Targeting the Gut Microbiota's Role in Host Energy Absorption With Precision Nutrition Interventions for the Prevention and Treatment of Obesity. Nutr Rev 2025:nuaf046. [PMID: 40233201 DOI: 10.1093/nutrit/nuaf046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/17/2025] Open
Abstract
The field of precision nutrition aims to develop dietary approaches based on individual biological factors such as genomics or the gut microbiota. The gut microbiota, which is the highly individualized and complex community of microbes residing in the colon, is a key contributor to human physiology. Although gut microbes play multiple roles in the metabolism of nutrients, their role in modulating the absorption of dietary energy from foods that escape digestion in the small intestine has the potential to variably affect energy balance and, thus, body weight. The fate of this energy, and its subsequent impact on body weight, is well described in rodents and is emerging in humans. This narrative review is focused on recent clinical evidence of the role of the gut microbiota in human energy balance, specifically its impact on energy available to the human host. Despite recent progress, remaining gaps in knowledge present opportunities for developing and implementing strategies to understand causal microbial mechanisms related to energy balance. We propose that implementing rigorous microbiota-focused measurements in the context of innovative clinical trial designs will elucidate integrated diet-host-gut microbiota mechanisms. These mechanisms are primed to be targets for precision nutrition interventions to optimize energy balance to achieve desired weight outcomes. Given the magnitude and impact of the obesity epidemic, implementing these interventions within comprehensive weight management paradigms has the potential to be of public health significance.
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Affiliation(s)
- Karen D Corbin
- AdventHealth Translational Research Institute, Orlando, FL 32804, United States
| | - Daria Igudesman
- AdventHealth Translational Research Institute, Orlando, FL 32804, United States
| | - Steven R Smith
- AdventHealth Translational Research Institute, Orlando, FL 32804, United States
| | - Karsten Zengler
- Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, United States
- Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, United States
- Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, United States
| | - Rosa Krajmalnik-Brown
- Biodesign Center for Health through Microbiomes, Arizona State University, Tempe, AZ 85281, United States
- School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ 85281, United States
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50
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Mishra S, Jain S, Agadzi B, Yadav H. A Cascade of Microbiota-Leaky Gut-Inflammation- Is it a Key Player in Metabolic Disorders? Curr Obes Rep 2025; 14:32. [PMID: 40208464 DOI: 10.1007/s13679-025-00624-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/21/2025] [Indexed: 04/11/2025]
Abstract
PURPOSE OF REVIEW This review addresses critical gaps in knowledge and provides a literature overview of the molecular pathways connecting gut microbiota dysbiosis to increased intestinal permeability (commonly referred to as "leaky gut") and its contribution to metabolic disorders. Restoring a healthy gut microbiota holds significant potential for enhancing intestinal barrier function and metabolic health. These interventions offer promising therapeutic avenues for addressing leaky gut and its associated pathologies in metabolic syndrome. RECENT FINDINGS In metabolic disorders such as obesity and type 2 diabetes (T2D), beneficial microbes such as those producing short-chain fatty acids (SCFAs) and other key metabolites like taurine, spermidine, glutamine, and indole derivatives are reduced. Concurrently, microbes that degrade toxic metabolites such as ethanolamine also decline, while proinflammatory, lipopolysaccharide (LPS)-enriched microbes increase. These microbial shifts place a higher burden on intestinal epithelial cells, which are in closest proximity to the gut lumen, inducing detrimental changes that compromise the structural and functional integrity of the intestinal barrier. Such changes include exacerbation of tight junction protein (TJP)s dysfunction, particularly through mechanisms such as destabilization of zona occludens (Zo)-1 mRNA or post-translational modifications. Emerging therapeutic strategies including ketogenic and Mediterranean diets, as well as probiotics, prebiotics, synbiotics, and postbiotics have demonstrated efficacy in restoring beneficial microbial populations, enhancing TJP expression and function, supporting gut barrier integrity, reducing leaky gut and inflammation, and ultimately improving metabolic disorders. This review summarizes the mechanisms by which gut microbiota contribute to the development of leaky gut and inflammation associated with metabolic syndrome. It also explores strategies for restoring gut microbiota balance and functionality by promoting beneficial microbes, increasing the production of beneficial metabolites, clearing toxic metabolites, and reducing the proportion of proinflammatory microbes. These approaches can alleviate the burden on intestinal epithelial cells, reduce leaky gut and inflammation, and improve metabolic health.
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Affiliation(s)
- Sidharth Mishra
- USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL, USA
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA
- Center for Excellence of Aging and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA
- Byrd Alzheimer's Institute, University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Shalini Jain
- USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL, USA
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA
- Center for Excellence of Aging and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA
- Byrd Alzheimer's Institute, University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Bryan Agadzi
- USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL, USA
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA
| | - Hariom Yadav
- USF Center for Microbiome Research, Microbiomes Institute, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
- Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
- Center for Excellence of Aging and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
- Byrd Alzheimer's Institute, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
- Director of USF Center for Microbiome Research, Microbiomes Institute, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, MDC78, Tampa, FL, 33612, USA.
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