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Yang SY, Han SM, Lee JY, Kim KS, Lee JE, Lee DW. Advancing Gut Microbiome Research: The Shift from Metagenomics to Multi-Omics and Future Perspectives. J Microbiol Biotechnol 2025; 35:e2412001. [PMID: 40223273 PMCID: PMC12010094 DOI: 10.4014/jmb.2412.12001] [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: 12/02/2024] [Revised: 02/14/2025] [Accepted: 02/24/2025] [Indexed: 04/15/2025]
Abstract
The gut microbiome, a dynamic and integral component of human health, has co-evolved with its host, playing essential roles in metabolism, immunity, and disease prevention. Traditional microbiome studies, primarily focused on microbial composition, have provided limited insights into the functional and mechanistic interactions between microbiota and their host. The advent of multi-omics technologies has transformed microbiome research by integrating genomics, transcriptomics, proteomics, and metabolomics, offering a comprehensive, systems-level understanding of microbial ecology and host-microbiome interactions. These advances have propelled innovations in personalized medicine, enabling more precise diagnostics and targeted therapeutic strategies. This review highlights recent breakthroughs in microbiome research, demonstrating how these approaches have elucidated microbial functions and their implications for health and disease. Additionally, it underscores the necessity of standardizing multi-omics methodologies, conducting large-scale cohort studies, and developing novel platforms for mechanistic studies, which are critical steps toward translating microbiome research into clinical applications and advancing precision medicine.
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Affiliation(s)
- So-Yeon Yang
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Seung Min Han
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Ji-Young Lee
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Kyoung Su Kim
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Jae-Eun Lee
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
| | - Dong-Woo Lee
- Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea
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Kipp ZA, Badmus OO, Stec DE, Hall B, Hinds TD. Bilirubin bioconversion to urobilin in the gut-liver-kidney axis: A biomarker for insulin resistance in the Cardiovascular-Kidney-Metabolic (CKM) Syndrome. Metabolism 2025; 163:156081. [PMID: 39580049 DOI: 10.1016/j.metabol.2024.156081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 10/17/2024] [Accepted: 11/16/2024] [Indexed: 11/25/2024]
Abstract
The rising rates of obesity worldwide have increased the incidence of cardiovascular disease (CVD), making it the number one cause of death. Higher plasma bilirubin levels have been shown to prevent metabolic dysfunction and CVD. However, reducing levels leads to deleterious outcomes, possibly due to reduced bilirubin half-life that escalates the production of its catabolized product, urobilinogen, produced by gut bacteria and naturally oxidized to urobilin. Recent findings suggest that the involvement of the microbiome catabolism of bilirubin to urobilin and its absorption via the hepatic portal vein contributes to CVD, suggesting a liver-gut axis involvement. We discuss the studies that demonstrate that urobilin is frequently raised in the urine of persons with CVD and its probable role in acquiring the disease. Urobilin is excreted from the kidneys into the urine and may serve as a biomarker for Cardiovascular-Kidney-Metabolic (CKM) Syndrome. We deliberate on the newly discovered bilirubin reductase (BilR) bacterial enzyme that produces urobilin. We discuss the bacterial species expressing BilR, how they impact CVD, and whether suppressing urobilin production and increasing bilirubin may provide new therapeutic strategies for CKM. Possible therapeutic mechanisms for achieving this goal are discussed.
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Affiliation(s)
- Zachary A Kipp
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Olufunto O Badmus
- Department of Physiology and Biophysics, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, USA
| | - David E Stec
- Department of Physiology and Biophysics, Cardiorenal, and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS, USA
| | - Brantley Hall
- Center for Bioinformatics and Computational Biology, Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, USA
| | - Terry D Hinds
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA.
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3
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Lee WH, Kipp ZA, Pauss SN, Martinez GJ, Bates EA, Badmus OO, Stec DE, Hinds TD. Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics. Clin Sci (Lond) 2025; 139:CS20242825. [PMID: 39873298 DOI: 10.1042/cs20242825] [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: 10/29/2024] [Revised: 12/18/2024] [Accepted: 12/20/2024] [Indexed: 01/30/2025]
Abstract
Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.6%. Shockingly, the global T2DM population is anticipated to double by 2050 compared with 2021. Prior studies indicate that oxidative stress and inflammation are instrumental in causing insulin resistance and instigating metabolic diseases. Numerous methods and drugs have been designed to combat insulin resistance, including metformin, thiazolidinediones (TZDs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA), and dipeptidyl peptidase 4 inhibitors (DPP4i). Bilirubin is an antioxidant with fat-burning actions by binding to the PPARα nuclear receptor transcription factor, improving insulin sensitivity, reducing inflammation, and reversing metabolic dysfunction. Potential treatment with antioxidants like bilirubin and increasing the enzyme that produces it, heme oxygenase (HMOX), has also gained attention. This review discusses the relationships between bilirubin, HMOX, and insulin sensitivity, how T2DM medications affect HMOX levels and activity, and potentially using bilirubin nanoparticles to treat insulin resistance. We explore the sex differences between these treatments in the HMOX system and how bilirubin levels are affected. We discuss the emerging concept that bilirubin bioconversion to urobilin may have a role in metabolic diseases. This comprehensive review summarizes our understanding of bilirubin functioning as a hormone, discusses the HMOX isoforms and their beneficial mechanisms, analyzes the sex differences that might cause a dichotomy in responses, and examines the potential use of HMOX and bilirubin nanoparticle therapies in treating metabolic diseases.
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Affiliation(s)
- Wang-Hsin Lee
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Zachary A Kipp
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Sally N Pauss
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Genesee J Martinez
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Evelyn A Bates
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
| | - Olufunto O Badmus
- Department of Physiology & Biophysics, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, USA
| | - David E Stec
- Department of Physiology & Biophysics, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, USA
| | - Terry D Hinds
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, USA
- Barnstable Brown Diabetes Center, University of Kentucky College of Medicine, Lexington, KY, USA
- Markey Cancer Center, University of Kentucky, Lexington, KY, USA
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Williams KI, Suryadevara P, Zhan CG, Hinds TD, Kipp ZA. Urobilin Derived from Bilirubin Bioconversion Binds Albumin and May Interfere with Bilirubin Interacting with Albumin: Implications for Disease Pathology. Biomedicines 2025; 13:302. [PMID: 40002715 PMCID: PMC11852593 DOI: 10.3390/biomedicines13020302] [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: 12/21/2024] [Revised: 01/19/2025] [Accepted: 01/24/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Bilirubin is a hydrophobic molecule that binds the carrier protein albumin for transport through systemic circulation. Bilirubin is cleared from the body through the liver and excreted into the intestines, where the microbiota modifies the chemical structure, forming urobilin, which can be reabsorbed into circulation by the hepatic portal vein. Urobilin has no known function. It is also unknown whether urobilin binds albumin for transport in circulation. We hypothesized that because of the likeness of their chemical structures, urobilin would also bind albumin like bilirubin does. Methods: First, we used in silico docking to predict if urobilin would bind to albumin and compared it to the bilirubin binding sites. To test this binding in vitro, we applied bilirubin's fluorescent property, which occurs when it is bound to a protein, including albumin, and exposed to light. We also used this method to determine if urobilin could exhibit autofluorescence when protein bound. Results: We found that bilirubin was predicted to bind albumin at amino acids E208, K212, D237, and K240 through hydrogen bonds. However, urobilin was predicted to bind albumin using different hydrogen bonds at amino acids H67, K240, and E252. We found that urobilin has a fluorescent property that can be quantified when bound to albumin. We performed a concentration response for urobilin-albumin fluorescent binding and observed a direct relationship between the urobilin level and the fluorescence intensity. Conclusions: The in silico docking analysis and autofluorescence results demonstrate that urobilin binds to albumin and might compete with bilirubin. This is the first study to identify a urobilin-binding protein and the important aspects of its physiological function and transport in circulation.
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Affiliation(s)
- Kevin I. Williams
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40508, USA;
- Department of Biochemistry and Molecular Biology, Centre College, Danville, KY 40422, USA
| | - Priyanka Suryadevara
- Department of Pharmaceutical Sciences and Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40508, USA; (P.S.); (C.-G.Z.)
| | - Chang-Guo Zhan
- Department of Pharmaceutical Sciences and Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40508, USA; (P.S.); (C.-G.Z.)
| | - Terry D. Hinds
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40508, USA;
- Markey Cancer Center, University of Kentucky, Lexington, KY 40508, USA
- Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY 40508, USA
| | - Zachary A. Kipp
- Drug & Disease Discovery D3 Research Center, Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40508, USA;
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Ramírez-Mejía MM, Castillo-Castañeda SM, Pal SC, Qi X, Méndez-Sánchez N. The Multifaceted Role of Bilirubin in Liver Disease: A Literature Review. J Clin Transl Hepatol 2024; 12:939-948. [PMID: 39544246 PMCID: PMC11557368 DOI: 10.14218/jcth.2024.00156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 09/19/2024] [Accepted: 10/08/2024] [Indexed: 11/17/2024] Open
Abstract
Bilirubin, the primary breakdown product of hemoproteins, particularly hemoglobin, plays a key role in the diagnosis, prognosis, and monitoring of liver diseases. In acute liver diseases, such as acute liver failure, drug-induced liver injury, and viral hepatitis, bilirubin serves as a biomarker reflecting the extent of hepatocyte loss and liver damage. Chronic liver diseases, including alcohol-related liver disease, chronic hepatitis C virus infection, metabolic dysfunction-associated fatty liver disease, and autoimmune liver diseases, are marked by persistent liver injury and inflammation. Bilirubin levels in chronic liver diseases provide insight into liver function, disease severity, and prognosis. As a versatile biomarker, bilirubin offers valuable information on the pathophysiology of liver diseases and aids in guiding clinical decision-making regarding the treatment of liver diseases and their complications. This review aimed to explore the multifunctional role of bilirubin in liver diseases by analyzing its biological functions beyond its role as a biomarker of liver damage.
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Affiliation(s)
- Mariana M. Ramírez-Mejía
- Plan of Combined Studies in Medicine (PECEM-MD/PhD), Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
- Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
| | - Stephany M. Castillo-Castañeda
- Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
- Medical, Dental and Health Sciences Master and Doctorate Program, National Autonomous University of Mexico, Mexico City, Mexico
| | - Shreya C. Pal
- Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
| | - Xingshun Qi
- Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning, China
| | - Nahum Méndez-Sánchez
- Liver Research Unit, Medica Sur Clinic & Foundation, Mexico City, Mexico
- Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico
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Kokkinias K, Sabag-Daigle A, Kim Y, Leleiwi I, Shaffer M, Kevorkian R, Daly RA, Wysocki VH, Borton MA, Ahmer BMM, Wrighton KC. Time-resolved multi-omics reveals diverse metabolic strategies of Salmonella during diet-induced inflammation. mSphere 2024; 9:e0053424. [PMID: 39254340 PMCID: PMC11520297 DOI: 10.1128/msphere.00534-24] [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: 06/24/2024] [Accepted: 07/22/2024] [Indexed: 09/11/2024] Open
Abstract
With a rise in antibiotic resistance and chronic infection, the metabolic response of Salmonella enterica serovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. In this study, we use a multi-omics approach to identify the metabolic response of Salmonella enterica serovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparing Salmonella gene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation in high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity in samples based on Salmonella ribosomal activity, which is separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expressions descriptive of each phase. Surprisingly, we identified genes associated with host cell entry expressed throughout infection, suggesting subpopulations of Salmonella or stress-induced dysregulation. Collectively, these results highlight not only the sensitivity of Salmonella to its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection.IMPORTANCEIdentifying novel therapeutic strategies for Salmonella infection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts toward Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation for Salmonella. We observed differential gene expression across infection phases in mice over time on a high-fat diet. Together, these findings reveal the metabolic tuning of Salmonella to dietary and temporal perturbations. Research like this, which explores the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.
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Affiliation(s)
- Katherine Kokkinias
- Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA
| | - Anice Sabag-Daigle
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USA
| | - Yongseok Kim
- Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA
| | - Ikaia Leleiwi
- Department of Cell and Molecular Biology, Colorado State University, Fort Collins, Colorado, USA
| | - Michael Shaffer
- Department of Soil and Crop Sciences, Colorado State University, Fort Collins, Colorado, USA
| | - Richard Kevorkian
- Department of Soil and Crop Sciences, Colorado State University, Fort Collins, Colorado, USA
| | - Rebecca A. Daly
- Department of Soil and Crop Sciences, Colorado State University, Fort Collins, Colorado, USA
| | - Vicki H. Wysocki
- Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, USA
| | - Mikayla A. Borton
- Department of Soil and Crop Sciences, Colorado State University, Fort Collins, Colorado, USA
| | - Brian M. M. Ahmer
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, USA
| | - Kelly C. Wrighton
- Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA
- Department of Cell and Molecular Biology, Colorado State University, Fort Collins, Colorado, USA
- Department of Soil and Crop Sciences, Colorado State University, Fort Collins, Colorado, USA
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Cheng T, Wen P, Yu R, Zhang F, Li H, Xu X, Zhao D, Liu F, Su W, Zheng Z, Yang H, Yao J, Jin L. Integrative microbiome and metabolome profiles reveal the impacts of periodontitis via oral-gut axis in first-trimester pregnant women. J Transl Med 2024; 22:819. [PMID: 39227984 PMCID: PMC11370083 DOI: 10.1186/s12967-024-05579-9] [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: 05/24/2024] [Accepted: 08/04/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND Periodontitis results from host-microbe dysbiosis and the resultant dysregulated immunoinflammatory response. Importantly, it closely links to numerous systemic comorbidities, and perplexingly contributes to adverse pregnancy outcomes (APOs). Currently, there are limited studies on the distal consequences of periodontitis via oral-gut axis in pregnant women. This study investigated the integrative microbiome-metabolome profiles through multi-omics approaches in first-trimester pregnant women and explored the translational potentials. METHODS We collected samples of subgingival plaques, saliva, sera and stool from 54 Chinese pregnant women at the first trimester, including 31 maternal periodontitis (Perio) subjects and 23 Non-Perio controls. By integrating 16S rRNA sequencing, untargeted metabolomics and clinical traits, we explored the oral-gut microbial and metabolic connection resulting from periodontitis among early pregnant women. RESULTS We demonstrated a novel bacterial distinguisher Coprococcus from feces of periodontitis subjects in association with subgingival periodontopathogens, being different from other fecal genera in Lachnospiraceae family. The ratio of fecal Coprococcus to Lachnoclostridium could discriminate between Perio and Non-Perio groups as the ratio of subgingival Porphyromonas to Rothia did. Furthermore, there were differentially abundant fecal metabolic features pivotally enriched in periodontitis subjects like L-urobilin and kynurenic acid. We revealed a periodontitis-oriented integrative network cluster, which was centered with fecal Coprococcus and L-urobilin as well as serum triglyceride. CONCLUSIONS The current findings about the notable influence of periodontitis on fecal microbiota and metabolites in first-trimester pregnant women via oral-gut axis signify the importance and translational implications of preconceptional oral/periodontal healthcare for enhancing maternal wellbeing.
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Affiliation(s)
- Tianfan Cheng
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
| | - Ping Wen
- Institute of Maternal and Child Medicine & Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Rong Yu
- Institute of Maternal and Child Medicine & Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Feng Zhang
- Division of Stomatology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Huijun Li
- Division of Stomatology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Xiaoyi Xu
- Institute of Maternal and Child Medicine & Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
- Center for Disease Control and Prevention, Shenzhen, China
| | - Dan Zhao
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
- Department of Implant Dentistry, Beijing Stomatological Hospital, Capital Medical University, Beijing, China
| | - Fang Liu
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Weilan Su
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Zheng Zheng
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Hong Yang
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Jilong Yao
- Division of Obstetrics & Gynecology, Shenzhen Maternity & Child Healthcare Hospital, Shenzhen, China
| | - Lijian Jin
- Division of Periodontology & Implant Dentistry, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
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Fan YN, Chi X, Yan L, Pu ZY, Yang JJ, Zhang YN. Lycium barbarum polysaccharides regulate the gut microbiota to modulate metabolites in high-fat diet-induced obese rats. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2024; 26:1115-1129. [PMID: 38952165 DOI: 10.1080/10286020.2024.2355130] [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: 02/10/2023] [Revised: 04/29/2024] [Accepted: 04/30/2024] [Indexed: 07/03/2024]
Abstract
Lycium Barbarum Polysaccharides (LBP) can benefit lipid parameters such as total cholesterol, triglyceride, and high-density lipoprotein levels and upregulate the level of Firmicutes, increase the diversity of gut microbiota and reduce metabolic disorders, finally relieving weight gain of obese rats. But it cannot reverse the outcome of obesity. Over 30 differential metabolites and four pathways are altered by LBP.
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Affiliation(s)
- Yan-Na Fan
- Department of Nutrition and Food Hygiene, School of Public Health, Ningxia Medical University, Yinchuan 750004, China
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan 750004, China
| | - Xi Chi
- Department of Nutrition and Food Hygiene, School of Public Health, Ningxia Medical University, Yinchuan 750004, China
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan 750004, China
| | - Lu Yan
- Department of Nutrition and Food Hygiene, School of Public Health, Ningxia Medical University, Yinchuan 750004, China
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan 750004, China
| | - Zhi-Yu Pu
- Department of Nutrition and Food Hygiene, School of Public Health, Ningxia Medical University, Yinchuan 750004, China
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan 750004, China
| | - Jian-Jun Yang
- Department of Nutrition and Food Hygiene, School of Public Health, Ningxia Medical University, Yinchuan 750004, China
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan 750004, China
| | - Yan-Nan Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Ningxia Medical University, Yinchuan 750004, China
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan 750004, China
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Zeng G, Zeng L, Wang Y, Cao Z, Zeng X, Xue Z, Liu S, Li Y, He L. Correlation between gut microbiota characteristics and non-small cell lung cancer based on macrogenomics sequencing. Hereditas 2024; 161:26. [PMID: 39192352 DOI: 10.1186/s41065-024-00328-w] [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: 05/31/2024] [Accepted: 07/24/2024] [Indexed: 08/29/2024] Open
Abstract
OBJECTIVE Non-small cell lung cancer (NSCLC) patients undergoing chemotherapy and immunotherapy experience disturbances in the gut microbiota. This study intends to find out the correlation between gut microbiota and clinical indices before and after radiotherapy for NSCLC. METHODS Ten patients with primary NSCLC were screened, and plasma and fecal samples were collected before and after radiotherapy, respectively. Inflammatory indices in plasma were detected. Genomic DNA was extracted from fecal specimens and sequenced on on Illumina HiSeq2000 sequencing platform. Thee sequenced data were subjected to Metagenome assembly, gene prediction, species annotation, and gene function analysis to study and analyze gut microbiota and metabolic functions. The correlation between the diversity of gut microbiota and the clinical indicators of NSCLC patients was evaluated, and the changes of gut microbiota before and after radiotherapy were observed. RESULTS The diversity of gut microbiota in NSCLC patients did not correlate with smoking, pathology, and inflammatory markers. The abundance of phylum (p)_Bacteroidetes increased; p_Firmicutes and p_Bacteroidetes accounted for the highest proportion in NSCLC patients, and the abundance of both was dominantly exchanged after radiotherapy. There was a decrease in genus (g)_Bifidobacterium after radiotherapy in NSCLC patients. There was no significant correlation between the diversity of gut microbiota after radiotherapy and radiotherapy sensitivity, and the structural composition and abundance of gut microbiota remained stable. CONCLUSION The diversity of gut microbiota is altered after radiotherapy in NSCLC patients, showing an increase in harmful bacteria and a decrease in beneficial bacteria.
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Affiliation(s)
- GuiLin Zeng
- Department of Oncology, The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital, University of Traditional Chinese Medicine), No.33, Mashi Street, Wenjiang District, Chengdu City, Sichuan Province, 611130, China
| | - LiRong Zeng
- Chengdu Railway Health School, Chengdu City, Sichuan Province, 611741, China
| | - Ying Wang
- Department of Oncology, The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital, University of Traditional Chinese Medicine), No.33, Mashi Street, Wenjiang District, Chengdu City, Sichuan Province, 611130, China
| | - Zhi Cao
- Department of Oncology, The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital, University of Traditional Chinese Medicine), No.33, Mashi Street, Wenjiang District, Chengdu City, Sichuan Province, 611130, China
| | - XiangHua Zeng
- Department of Oncology, The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital, University of Traditional Chinese Medicine), No.33, Mashi Street, Wenjiang District, Chengdu City, Sichuan Province, 611130, China
| | - ZhiHong Xue
- Department of Oncology, The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital, University of Traditional Chinese Medicine), No.33, Mashi Street, Wenjiang District, Chengdu City, Sichuan Province, 611130, China
| | - ShiLan Liu
- Department of Oncology, The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital, University of Traditional Chinese Medicine), No.33, Mashi Street, Wenjiang District, Chengdu City, Sichuan Province, 611130, China
| | - YaMao Li
- Department of Oncology, The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital, University of Traditional Chinese Medicine), No.33, Mashi Street, Wenjiang District, Chengdu City, Sichuan Province, 611130, China
| | - Lang He
- Department of Oncology, The Second Clinical Medical College, Affiliated Fifth People's Hospital of Chengdu, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People's Hospital, University of Traditional Chinese Medicine), No.33, Mashi Street, Wenjiang District, Chengdu City, Sichuan Province, 611130, China.
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10
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Hartmann A, Binder T, Rothballer M. Quorum sensing-related activities of beneficial and pathogenic bacteria have important implications for plant and human health. FEMS Microbiol Ecol 2024; 100:fiae076. [PMID: 38744663 PMCID: PMC11149725 DOI: 10.1093/femsec/fiae076] [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: 01/23/2024] [Revised: 03/28/2024] [Accepted: 05/13/2024] [Indexed: 05/16/2024] Open
Abstract
Eukaryotic organisms coevolved with microbes from the environment forming holobiotic meta-genomic units. Members of host-associated microbiomes have commensalic, beneficial/symbiotic, or pathogenic phenotypes. More than 100 years ago, Lorenz Hiltner, pioneer of soil microbiology, introduced the term 'Rhizosphere' to characterize the observation that a high density of saprophytic, beneficial, and pathogenic microbes are attracted by root exudates. The balance between these types of microbes decide about the health of the host. Nowadays we know, that for the interaction of microbes with all eukaryotic hosts similar principles and processes of cooperative and competitive functions are in action. Small diffusible molecules like (phyto)hormones, volatiles and quorum sensing signals are examples for mediators of interspecies and cross-kingdom interactions. Quorum sensing of bacteria is mediated by different autoinducible metabolites in a density-dependent manner. In this perspective publication, the role of QS-related activities for the health of hosts will be discussed focussing mostly on N-acyl-homoserine lactones (AHL). It is also considered that in some cases very close phylogenetic relations exist between plant beneficial and opportunistic human pathogenic bacteria. Based on a genome and system-targeted new understanding, sociomicrobiological solutions are possible for the biocontrol of diseases and the health improvement of eukaryotic hosts.
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Affiliation(s)
- Anton Hartmann
- Faculty of Biology, Microbe-Host Interactions, Ludwig-Maximilian-University Munich, Grosshaderner Str. 2, D-82152 Planegg/Martinsried, Germany
- Department of Environmental Sciences, Helmholtz Zentrum Munich, German Research Center for Health and Environment, Research Unit Microbe-Plant Interactions, Ingolstädter Landstr. 1, D-85762 Neuherberg, Germany
| | - Tatiana Binder
- Department of Environmental Sciences, Helmholtz Zentrum Munich, German Research Center for Health and Environment, Research Unit Microbe-Plant Interactions, Ingolstädter Landstr. 1, D-85762 Neuherberg, Germany
| | - Michael Rothballer
- Department of Environmental Sciences, Helmholtz Zentrum Munich, German Research Center for Health and Environment, Research Unit Microbe-Plant Interactions, Ingolstädter Landstr. 1, D-85762 Neuherberg, Germany
- Helmholtz Zentrum Munich, German Research Center for Health and Environment, Institute of Network Biology, Ingolstädter Landstr. 1 D-85762 Neuherberg, Germany
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11
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Hou J, Lu L, Lian L, Tian Y, Zeng T, Ma Y, Li S, Chen L, Xu W, Gu T, Li G, Liu X. Effects of coated sodium butyrate on the growth performance, serum biochemistry, antioxidant capacity, intestinal morphology, and intestinal microbiota of broiler chickens. Front Microbiol 2024; 15:1368736. [PMID: 38650870 PMCID: PMC11033381 DOI: 10.3389/fmicb.2024.1368736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 03/28/2024] [Indexed: 04/25/2024] Open
Abstract
Introduction This study examined the impact of adding coated sodium butyrate (CSB) to the diet on the growth performance, serum biochemistry, antioxidant capacity, intestinal morphology, and cecal microbiota of yellow-feathered broiler chickens. Methods In this study, 240 yellow-feathered broiler chickens at 26 days old were divided into two groups: the control group (CON group) received a standard diet, and the experimental group (CSB group) received a diet with 0.5 g/kg of a supplement called CSB. Each group had 6 replicates, with 20 chickens in each replicate, and the experiment lasted for 36 days. Results Compared to the CON group, the CSB group showed a slight but insignificant increase in average daily weight gain during the 26-62 day period, while feed intake significantly decreased. The CSB group exhibited significant increases in serum superoxide dismutase, catalase, and total antioxidant capacity. Additionally, the CSB group had significant increases in total protein and albumin content, as well as a significant decrease in blood ammonia levels. Compared to the CON group, the CSB group had significantly increased small intestine villus height and significantly decreased jejunal crypt depth. The abundance of Bacteroidetes and Bacteroides in the cecal microbiota of the CSB group was significantly higher than that of the CON group, while the abundance of Proteobacteria, Deferribacteres, and Epsilonbacteraeota was significantly lower than that of the CON group. Conclusion These results suggest that adding CSB to the diet can improve the growth performance and antioxidant capacity of yellow-feathered broiler chickens while maintaining intestinal health.
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Affiliation(s)
- Jinwang Hou
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Lizhi Lu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Lina Lian
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Yong Tian
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Tao Zeng
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Yanfen Ma
- College of Standardization, China Jiliang University, Hangzhou, China
| | - Sisi Li
- College of Standardization, China Jiliang University, Hangzhou, China
| | - Li Chen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Wenwu Xu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Tiantian Gu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Guoqin Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Xin Liu
- College of Standardization, China Jiliang University, Hangzhou, China
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12
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Kokkinias K, Sabag-Daigle A, Kim Y, Leleiwi I, Shaffer M, Kevorkian R, Daly RA, Wysocki VH, Borton MA, Ahmer BMM, Wrighton KC. Time resolved multi-omics reveals diverse metabolic strategies of Salmonella during diet-induced inflammation. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.02.03.578763. [PMID: 38352409 PMCID: PMC10862859 DOI: 10.1101/2024.02.03.578763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/25/2024]
Abstract
With a rise in antibiotic resistance and chronic infection, the metabolic response of Salmonella enterica serovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. Here, we use a multi-omics approach to identify the metabolic response of Salmonella enterica serovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparing Salmonella gene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation of the high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity of samples based on Salmonella ribosomal activity, which separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expression descriptive of each phase. Surprisingly, we identified genes associated with host-cell entry expressed throughout infection, suggesting sub-populations of Salmonella or stress-induced dysregulation. Collectively, these results highlight not only the sensitivity of Salmonella to its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection. Importance Identifying novel therapeutic strategies for Salmonella infection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts towards Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation for Salmonella . Over time on a high-fat diet, we observed differential gene expression across infection phases. Together, these findings reveal the metabolic tuning of Salmonella to dietary and temporal perturbations. Research like this, exploring the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.
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13
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Yong GJM, Porsche CE, Sitarik AR, Fujimura KE, McCauley K, Nguyen DT, Levin AM, Woodcroft KJ, Ownby DR, Rundle AG, Johnson CC, Cassidy-Bushrow A, Lynch SV. Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk. Gut Microbes 2024; 16:2290661. [PMID: 38117587 PMCID: PMC10761186 DOI: 10.1080/19490976.2023.2290661] [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] [Received: 08/01/2023] [Accepted: 11/29/2023] [Indexed: 12/22/2023] Open
Abstract
Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort (n = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals. In vitro, exposure of enterocytes to fecal extracts from higher-risk infants led to upregulation of genes associated with obesity and with expansion of nutrient sensing enteroendocrine progenitor cells. Fecal extracts from higher-risk infants also promoted enterocyte barrier dysfunction. These data implicate dysregulation of infant microbiome functional development, and more specifically promotion of enteroendocrine signaling and epithelial barrier impairment in the early-life developmental origins of childhood obesity.
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Affiliation(s)
- Germaine J. M. Yong
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
- Asian Microbiome Library Pte Ltd, Singapore and Singapore Institute of Food and Biotechnology Innovation, Singapore, Singapore
| | - Cara E. Porsche
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Alexandra R. Sitarik
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - Kei E. Fujimura
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
- Genetic Disease Laboratory, California Department of Public Health, San Francisco, CA, USA
| | - Kathryn McCauley
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Dat T. Nguyen
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Albert M. Levin
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | | | - Dennis R. Ownby
- Division of Allergy and Clinical Immunology, Department of Pediatrics, Augusta University, Augusta, GA, USA
| | - Andrew G. Rundle
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Christine C. Johnson
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | | | - Susan V. Lynch
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
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14
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Bloemendaal M, Veniaminova E, Anthony DC, Gorlova A, Vlaming P, Khairetdinova A, Cespuglio R, Lesch KP, Arias Vasquez A, Strekalova T. Serotonin Transporter (SERT) Expression Modulates the Composition of the Western-Diet-Induced Microbiota in Aged Female Mice. Nutrients 2023; 15:3048. [PMID: 37447374 PMCID: PMC10346692 DOI: 10.3390/nu15133048] [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: 06/09/2023] [Revised: 06/27/2023] [Accepted: 06/29/2023] [Indexed: 07/15/2023] Open
Abstract
Background. The serotonin transporter (SERT), highly expressed in the gut and brain, is implicated in metabolic processes. A genetic variant of the upstream regulatory region of the SLC6A4 gene encoding SERT, the so-called short (s) allele, in comparison with the long (l) allele, results in the decreased function of this transporter, altered serotonergic regulation, an increased risk of psychiatric pathology and type-2 diabetes and obesity, especially in older women. Aged female mice with the complete (Sert-/-: KO) or partial (Sert+/-: HET) loss of SERT exhibit more pronounced negative effects following their exposure to a Western diet in comparison to wild-type (Sert+/+: WT) animals. Aims. We hypothesized that these effects might be mediated by an altered gut microbiota, which has been shown to influence serotonin metabolism. We performed V4 16S rRNA sequencing of the gut microbiota in 12-month-old WT, KO and HET female mice that were housed on a control or Western diet for three weeks. Results. The relative abundance of 11 genera was increased, and the abundance of 6 genera was decreased in the Western-diet-housed mice compared to the controls. There were correlations between the abundance of Streptococcus and Ruminococcaceae_UCG-014 and the expression of the pro-inflammatory marker Toll-like-Receptor 4 (Tlr4) in the dorsal raphe, as well as the expression of the mitochondrial activity marker perixome-proliferator-activated-receptor-cofactor-1b (Ppargc1b) in the prefrontal cortex. Although there was no significant impact of genotype on the microbiota in animals fed with the Control diet, there were significant interactions between diet and genotype. Following FDR correction, the Western diet increased the relative abundance of Intestinimonas and Atopostipes in the KO animals, which was not observed in the other groups. Erysipelatoclostridium abundance was increased by the Western diet in the WT group but not in HET or KO animals. Conclusions. The enhanced effects of a challenge with a Western diet in SERT-deficient mice include the altered representation of several gut genera, such as Intestinimonas, Atopostipes and Erysipelatoclostridium, which are also implicated in serotonergic and lipid metabolism. The manipulation of these genera may prove useful in individuals with the short SERT allele.
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Affiliation(s)
- Mirjam Bloemendaal
- Departments of Psychiatry & Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (P.V.); (A.A.V.)
| | - Ekaterina Veniaminova
- Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia; (E.V.); (A.G.); (A.K.); (R.C.)
| | | | - Anna Gorlova
- Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia; (E.V.); (A.G.); (A.K.); (R.C.)
| | - Priscilla Vlaming
- Departments of Psychiatry & Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (P.V.); (A.A.V.)
| | - Adel Khairetdinova
- Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia; (E.V.); (A.G.); (A.K.); (R.C.)
| | - Raymond Cespuglio
- Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine and Department of Normal Physiology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia; (E.V.); (A.G.); (A.K.); (R.C.)
- Neuroscience Research Center of Lyon, Claude-Bernard Lyon-1 University, 69500 Bron, France
| | - Klaus Peter Lesch
- Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany; (K.P.L.); (T.S.)
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, 6229 HX Maastricht, The Netherlands
| | - Alejandro Arias Vasquez
- Departments of Psychiatry & Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; (P.V.); (A.A.V.)
| | - Tatyana Strekalova
- Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany; (K.P.L.); (T.S.)
- Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, 6229 HX Maastricht, The Netherlands
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15
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Usman M, Shi Z, Cai Y, Zhang S, Luo G. Microbial insights towards understanding the role of hydrochar in enhancing phenol degradation in anaerobic digestion. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 330:121779. [PMID: 37150345 DOI: 10.1016/j.envpol.2023.121779] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/29/2023] [Accepted: 05/05/2023] [Indexed: 05/09/2023]
Abstract
Anaerobic digestion (AD) of wastewater is the most promising bioprocess for organic conversion, however, phenol is toxic and resistant to anaerobic degradation. The current study compared the effect of hydrochar and granular activated carbon (GAC) on AD of phenol at four concentrations (100 mg/L, 250 mg/L, 500 mg/L and 1000 mg/L). Results demonstrated that hydrochar significantly improved the methane production rate and reduced the lag phase at all concentrations of phenol. The methane production rate was improved by about 50% at both 100 mg/L and 250 mg/L phenol, while it was raised by >160% at 500 mg/L and 1000 mg/L phenol by hydrochar. The GAC only increased the methane production rate at 500 mg/L and 1000 mg/L due to high adsorption capacity. Further, the adsorption of phenol by hydrochar had no apparent impact on the methane production rate, even though certain amounts of phenol were adsorbed. At 500 mg/L, the amount of methane produced significantly increased, so 16S rRNA transcripts sequencing and metabolomic analysis were conducted. 16S rRNA transcripts sequencing analysis indicated that hydrochar resulted in the enrichment of syntrophic bacteria (e.g., Syntrophorhabdus &Syntrophobacter) and Methanosaeta, which might be related with direct interspecies electron transfer. Further, it was noticed that the growth of Methanobacterium was repressed at 500 mg/L phenol, while hydrochar promoted its growth. Phenol was degraded into L-tyrosine and then followed the benzoate degradation pathway for methane production as revealed by metabolomic analysis. In addition, metabolomic analysis also revealed that hydrochar promoted the degradation of all metabolites and enhanced the phenol degradation into methane.
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Affiliation(s)
- Muhammad Usman
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, China; Shanghai Technical Service Platform for Pollution Control and Resource Utilization of Organic Wastes, Shanghai, 200438, China; Department of Civil and Environmental Engineering, University of Alberta, Edmonton, AB T6G 2W2, Canada; Bioproducts, Sciences and Engineering Laboratory (BSEL), Washington State University, Tri-Cities, Richland, WA, 99354, United States.
| | - Zhijian Shi
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, China; Shanghai Technical Service Platform for Pollution Control and Resource Utilization of Organic Wastes, Shanghai, 200438, China
| | - Yafan Cai
- School of Chemical Engineering, Zhengzhou University, Ke xue Dadao 100, Zhengzhou, 450001, China
| | - Shicheng Zhang
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, China; Shanghai Technical Service Platform for Pollution Control and Resource Utilization of Organic Wastes, Shanghai, 200438, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai, 200092, China
| | - Gang Luo
- Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP3), Department of Environmental Science and Engineering, Fudan University, Shanghai, 200433, China; Shanghai Technical Service Platform for Pollution Control and Resource Utilization of Organic Wastes, Shanghai, 200438, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai, 200092, China.
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16
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Luo L, Chang Y, Sheng L. Gut-liver axis in the progression of nonalcoholic fatty liver disease: From the microbial derivatives-centered perspective. Life Sci 2023; 321:121614. [PMID: 36965522 DOI: 10.1016/j.lfs.2023.121614] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/16/2023] [Accepted: 03/18/2023] [Indexed: 03/27/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the world's most common chronic liver diseases. However, its pathogenesis remains unclear. With the deepening of research, NAFLD is considered a metabolic syndrome associated with the environment, heredity, and metabolic disorders. Recently, the close relationship between the intestinal microbiome and NAFLD has been discovered, and the theory of the "gut-liver axis" has been proposed. In short, the gut bacteria directly reach the liver via the portal vein through the damaged intestinal wall or indirectly participate in the development of NAFLD through signaling pathways mediated by their components and metabolites. This review focuses on the roles of microbiota-derived lipopolysaccharide, DNA, peptidoglycan, bile acids, short-chain fatty acids, endogenous ethanol, choline and its metabolites, indole and its derivatives, and bilirubin and its metabolites in the progression of NAFLD, which may provide significative insights into the pathogenesis, diagnosis, and treatment for this highly prevalent liver disease.
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Affiliation(s)
- Lijun Luo
- Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
| | - Yongchun Chang
- Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
| | - Li Sheng
- Department of Drug Metabolism, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China; Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
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17
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Bates EA, Kipp ZA, Martinez GJ, Badmus OO, Soundarapandian MM, Foster D, Xu M, Creeden JF, Greer JR, Morris AJ, Stec DE, Hinds TD. Suppressing Hepatic UGT1A1 Increases Plasma Bilirubin, Lowers Plasma Urobilin, Reorganizes Kinase Signaling Pathways and Lipid Species and Improves Fatty Liver Disease. Biomolecules 2023; 13:252. [PMID: 36830621 PMCID: PMC9953728 DOI: 10.3390/biom13020252] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 01/25/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
Several population studies have observed lower serum bilirubin levels in patients with non-alcoholic fatty liver disease (NAFLD). Yet, treatments to target this metabolic phenotype have not been explored. Therefore, we designed an N-Acetylgalactosamine (GalNAc) labeled RNAi to target the enzyme that clears bilirubin from the blood, the UGT1A1 glucuronyl enzyme (GNUR). In this study, male C57BL/6J mice were fed a high-fat diet (HFD, 60%) for 30 weeks to induce NAFLD and were treated subcutaneously with GNUR or sham (CTRL) once weekly for six weeks while continuing the HFD. The results show that GNUR treatments significantly raised plasma bilirubin levels and reduced plasma levels of the bilirubin catabolized product, urobilin. We show that GNUR decreased liver fat content and ceramide production via lipidomics and lowered fasting blood glucose and insulin levels. We performed extensive kinase activity analyses using our PamGene PamStation kinome technology and found a reorganization of the kinase pathways and a significant decrease in inflammatory mediators with GNUR versus CTRL treatments. These results demonstrate that GNUR increases plasma bilirubin and reduces plasma urobilin, reducing NAFLD and inflammation and improving overall liver health. These data indicate that UGT1A1 antagonism might serve as a treatment for NAFLD and may improve obesity-associated comorbidities.
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Affiliation(s)
- Evelyn A. Bates
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA
| | - Zachary A. Kipp
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA
| | - Genesee J. Martinez
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA
| | - Olufunto O. Badmus
- Department of Physiology & Biophysics, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | | | | | - Mei Xu
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA
| | - Justin F. Creeden
- Department of Neurosciences, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA
| | - Jennifer R. Greer
- Department of Physiology & Biophysics, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Andrew J. Morris
- Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
| | - David E. Stec
- Department of Physiology & Biophysics, Cardiorenal and Metabolic Diseases Research Center, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Terry D. Hinds
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40508, USA
- Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY 40508, USA
- Markey Cancer Center, University of Kentucky, Lexington, KY 40508, USA
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18
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Kipp ZA, Xu M, Bates EA, Lee WH, Kern PA, Hinds TD. Bilirubin Levels Are Negatively Correlated with Adiposity in Obese Men and Women, and Its Catabolized Product, Urobilin, Is Positively Associated with Insulin Resistance. Antioxidants (Basel) 2023; 12:170. [PMID: 36671031 PMCID: PMC9854555 DOI: 10.3390/antiox12010170] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 01/03/2023] [Accepted: 01/09/2023] [Indexed: 01/12/2023] Open
Abstract
Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein. We hypothesized that when bilirubin levels are decreased, the urobilin increases in the plasma of obese humans, as compared to lean humans. To test this, we measured plasma levels of bilirubin and urobilin, body mass index (BMI), adiposity, blood glucose and insulin, and HOMA IR in a small cohort of obese and lean men and women. We found that bilirubin levels negatively correlated with BMI and adiposity in obese men and women, as compared to their lean counterparts. Contrarily, urobilin levels were positively associated with adiposity and BMI. Only obese women were found to be insulin resistant based on significantly higher HOMA IR, as compared to lean women. The urobilin levels were positively associated with HOMA IR in both groups, but women had a stronger linear correlation. These studies indicate that plasma urobilin levels are associated with obesity and its comorbidities, such as insulin resistance.
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Affiliation(s)
- Zachary A. Kipp
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, 760 Press Avenue, Healthy Kentucky Research Building, Lexington, KY 40508, USA
| | - Mei Xu
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, 760 Press Avenue, Healthy Kentucky Research Building, Lexington, KY 40508, USA
| | - Evelyn A. Bates
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, 760 Press Avenue, Healthy Kentucky Research Building, Lexington, KY 40508, USA
| | - Wang-Hsin Lee
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, 760 Press Avenue, Healthy Kentucky Research Building, Lexington, KY 40508, USA
| | - Philip A. Kern
- Department of Internal Medicine, Division of Endocrinology, University of Kentucky, Lexington, KY 40508, USA
| | - Terry D. Hinds
- Department of Pharmacology and Nutritional Sciences, University of Kentucky, 760 Press Avenue, Healthy Kentucky Research Building, Lexington, KY 40508, USA
- Barnstable Brown Diabetes Center, University of Kentucky, Lexington, KY 40508, USA
- Markey Cancer Center, University of Kentucky, Lexington, KY 40508, USA
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19
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Yan G, Li S, Wen Y, Luo Y, Huang J, Chen B, Lv S, Chen L, He L, He M, Yang Q, Yu Z, Xiao W, Tang Y, Li W, Han J, Zhao F, Yu S, Kong F, Abbasi B, Yin H, Gu C. Characteristics of intestinal microbiota in C57BL/6 mice with non-alcoholic fatty liver induced by high-fat diet. Front Microbiol 2022; 13:1051200. [PMID: 36620001 PMCID: PMC9813237 DOI: 10.3389/fmicb.2022.1051200] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 11/25/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction As a representation of the gut microbiota, fecal and cecal samples are most often used in human and animal studies, including in non-alcoholic fatty liver disease (NAFLD) research. However, due to the regional structure and function of intestinal microbiota, whether it is representative to use cecal or fecal contents to study intestinal microbiota in the study of NAFLD remains to be shown. Methods The NAFLD mouse model was established by high-fat diet induction, and the contents of the jejunum, ileum, cecum, and colon (formed fecal balls) were collected for 16S rRNA gene analysis. Results Compared with normal mice, the diversity and the relative abundance of major bacteria and functional genes of the ileum, cecum and colon were significantly changed, but not in the jejunum. In NAFLD mice, the variation characteristics of microbiota in the cecum and colon (feces) were similar. However, the variation characteristics of intestinal microbiota in the ileum and large intestine segments (cecum and colon) were quite different. Discussion Therefore, the study results of cecal and colonic (fecal) microbiota cannot completely represent the results of jejunal and ileal microbiota.
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Affiliation(s)
- Guangwen Yan
- College of Animal Science, Xichang University, Xichang, China
| | - Shuaibing Li
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Yuhang Wen
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Yadan Luo
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Jingrong Huang
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Baoting Chen
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Shuya Lv
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Lang Chen
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Lvqin He
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Manli He
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Qian Yang
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Zehui Yu
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Wudian Xiao
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Yong Tang
- Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China,State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, China
| | - Weiyao Li
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Jianhong Han
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Fangfang Zhao
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Shumin Yu
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Fang Kong
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China
| | - Benazir Abbasi
- College of Veterinary Medicine, Nanjing Agricultural University, Jiangsu, China
| | - Hongmei Yin
- College of Animal Science, Xichang University, Xichang, China,*Correspondence: Hongmei Yin,
| | - Congwei Gu
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China,Model Animal and Human Disease Research of Luzhou Key Laboratory, Luzhou, China,College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China,Congwei Gu,
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20
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Lund PJ, Gates LA, Leboeuf M, Smith SA, Chau L, Lopes M, Friedman ES, Saiman Y, Kim MS, Shoffler CA, Petucci C, Allis CD, Wu GD, Garcia BA. Stable isotope tracing in vivo reveals a metabolic bridge linking the microbiota to host histone acetylation. Cell Rep 2022; 41:111809. [PMID: 36516747 PMCID: PMC9994635 DOI: 10.1016/j.celrep.2022.111809] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 03/09/2022] [Accepted: 11/17/2022] [Indexed: 12/14/2022] Open
Abstract
The gut microbiota influences acetylation on host histones by fermenting dietary fiber into butyrate. Although butyrate could promote histone acetylation by inhibiting histone deacetylases, it may also undergo oxidation to acetyl-coenzyme A (CoA), a necessary cofactor for histone acetyltransferases. Here, we find that epithelial cells from germ-free mice harbor a loss of histone H4 acetylation across the genome except at promoter regions. Using stable isotope tracing in vivo with 13C-labeled fiber, we demonstrate that the microbiota supplies carbon for histone acetylation. Subsequent metabolomic profiling revealed hundreds of labeled molecules and supported a microbial contribution to host fatty acid metabolism, which declined in response to colitis and correlated with reduced expression of genes involved in fatty acid oxidation. These results illuminate the flow of carbon from the diet to the host via the microbiota, disruptions to which may affect energy homeostasis in the distal gut and contribute to the development of colitis.
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Affiliation(s)
- Peder J Lund
- Department of Biochemistry and Biophysics, Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Leah A Gates
- Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA
| | - Marylene Leboeuf
- Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA
| | - Sarah A Smith
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Lillian Chau
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Mariana Lopes
- Department of Biochemistry and Biophysics, Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Elliot S Friedman
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Yedidya Saiman
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Min Soo Kim
- Metabolomics Core, Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Clarissa A Shoffler
- Metabolomics Core, Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Christopher Petucci
- Metabolomics Core, Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - C David Allis
- Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065, USA
| | - Gary D Wu
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Benjamin A Garcia
- Department of Biochemistry and Biophysics, Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
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21
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Traquete F, Luz J, Cordeiro C, Sousa Silva M, Ferreira AEN. Graph Properties of Mass-Difference Networks for Profiling and Discrimination in Untargeted Metabolomics. Front Mol Biosci 2022; 9:917911. [PMID: 35936789 PMCID: PMC9353772 DOI: 10.3389/fmolb.2022.917911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/03/2022] [Indexed: 11/16/2022] Open
Abstract
Untargeted metabolomics seeks to identify and quantify most metabolites in a biological system. In general, metabolomics results are represented by numerical matrices containing data that represent the intensities of the detected variables. These matrices are subsequently analyzed by methods that seek to extract significant biological information from the data. In mass spectrometry-based metabolomics, if mass is detected with sufficient accuracy, below 1 ppm, it is possible to derive mass-difference networks, which have spectral features as nodes and chemical changes as edges. These networks have previously been used as means to assist formula annotation and to rank the importance of chemical transformations. In this work, we propose a novel role for such networks in untargeted metabolomics data analysis: we demonstrate that their properties as graphs can also be used as signatures for metabolic profiling and class discrimination. For several benchmark examples, we computed six graph properties and we found that the degree profile was consistently the property that allowed for the best performance of several clustering and classification methods, reaching levels that are competitive with the performance using intensity data matrices and traditional pretreatment procedures. Furthermore, we propose two new metrics for the ranking of chemical transformations derived from network properties, which can be applied to sample comparison or clustering. These metrics illustrate how the graph properties of mass-difference networks can highlight the aspects of the information contained in data that are complementary to the information extracted from intensity-based data analysis.
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22
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Wang L, Li F, Gu B, Qu P, Liu Q, Wang J, Tang J, Cai S, Zhao Q, Ming Z. Metaomics in Clinical Laboratory: Potential Driving Force for Innovative Disease Diagnosis. Front Microbiol 2022; 13:883734. [PMID: 35783436 PMCID: PMC9247514 DOI: 10.3389/fmicb.2022.883734] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 05/18/2022] [Indexed: 11/13/2022] Open
Abstract
Currently, more and more studies suggested that reductionism was lack of holistic and integrative view of biological processes, leading to limited understanding of complex systems like microbiota and the associated diseases. In fact, microbes are rarely present in individuals but normally live in complex multispecies communities. With the recent development of a variety of metaomics techniques, microbes could be dissected dynamically in both temporal and spatial scales. Therefore, in-depth understanding of human microbiome from different aspects such as genomes, transcriptomes, proteomes, and metabolomes could provide novel insights into their functional roles, which also holds the potential in making them diagnostic biomarkers in many human diseases, though there is still a huge gap to fill for the purpose. In this mini-review, we went through the frontlines of the metaomics techniques and explored their potential applications in clinical diagnoses of human diseases, e.g., infectious diseases, through which we concluded that novel diagnostic methods based on human microbiomes shall be achieved in the near future, while the limitations of these techniques such as standard procedures and computational challenges for rapid and accurate analysis of metaomics data in clinical settings were also examined.
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Affiliation(s)
- Liang Wang
- Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, China
| | - Fen Li
- Department of Laboratory Medicine, Huaiyin Hospital, Huai’an, China
| | - Bin Gu
- Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, China
| | - Pengfei Qu
- The First School of Clinical Medicine, Xuzhou Medical University, Xuzhou, China
| | - Qinghua Liu
- State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macao SAR, China
| | - Junjiao Wang
- Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, China
| | - Jiawei Tang
- Department of Bioinformatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, China
| | - Shubin Cai
- College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China
| | - Qi Zhao
- School of Computer Science and Software Engineering, University of Science and Technology Liaoning, Anshan, China
- *Correspondence: Qi Zhao,
| | - Zhong Ming
- College of Computer Science and Software Engineering, Shenzhen University, Shenzhen, China
- Zhong Ming,
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23
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Gu C, Zhou Z, Yu Z, He M, He L, Luo Z, Xiao W, Yang Q, Zhao F, Li W, Shen L, Han J, Cao S, Zuo Z, Deng J, Yan Q, Ren Z, Zhao M, Yu S. The Microbiota and It’s Correlation With Metabolites in the Gut of Mice With Nonalcoholic Fatty Liver Disease. Front Cell Infect Microbiol 2022; 12:870785. [PMID: 35694542 PMCID: PMC9186341 DOI: 10.3389/fcimb.2022.870785] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 04/25/2022] [Indexed: 11/17/2022] Open
Abstract
In recent years, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the world. As an important model animal, the characteristics of gut microbiota alteration in mice with NAFLD have been studied but the changes in metabolite abundance in NAFLD mice and how the gut microbiota affects these intestinal metabolites remain unclear. In this experiment, a mouse model for NAFLD was established by a high-fat diet. The use of 16S rDNA technology showed that while there were no significant changes in the alpha diversity in the cecum of NAFLD mice, the beta diversity changed significantly. The abundance of Blautia, Unidentified-Lachnospiraceae, Romboutsia, Faecalibaculum, and Ileibacterium increased significantly in NAFLD mice, while Allobaculum and Enterorhabdus decreased significantly. Amino acids, lipids, bile acids and nucleotide metabolites were among the 167 significantly different metabolites selected. The metabolic pathways of amino acids, SFAs, and bile acids were significantly enhanced, while the metabolic pathways of PUFAs, vitamins, and nucleotides were significantly inhibited. Through correlation and MIMOSA2 analysis, it is suggested that gut microbiota does not affect the changes of lipids and bile acids but can reduce thiamine, pyridoxine, and promote L-phenylalanine and tyramine production. The findings of this study will help us to better understand the relationship between gut microbiota and metabolites in NAFLD.
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Affiliation(s)
- Congwei Gu
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China
| | - Zihan Zhou
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Zehui Yu
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China
| | - Manli He
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China
| | - Lvqin He
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China
| | - Zhengzhong Luo
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Wudian Xiao
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China
| | - Qian Yang
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China
| | - Fangfang Zhao
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Weiyao Li
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Liuhong Shen
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Jianhong Han
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China
| | - Suizhong Cao
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Zhicai Zuo
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Junliang Deng
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Qigui Yan
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Zhihua Ren
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
| | - Mingde Zhao
- Laboratory Animal Centre, Southwest Medical University, Luzhou, China
- *Correspondence: Mingde Zhao, ; Shumin Yu,
| | - Shumin Yu
- College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China
- *Correspondence: Mingde Zhao, ; Shumin Yu,
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24
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Bravo Iniguez A, Tian Q, Du M, Zhu MJ. Alpha-Ketoglutarate Promotes Goblet Cell Differentiation and Alters Urea Cycle Metabolites in DSS-Induced Colitis Mice. Nutrients 2022; 14:nu14061148. [PMID: 35334805 PMCID: PMC8951758 DOI: 10.3390/nu14061148] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/23/2022] [Accepted: 03/04/2022] [Indexed: 12/04/2022] Open
Abstract
The metabolite, alpha-ketoglutarate (aKG), shows promise as an approach for ameliorating colitis, but much remains unknown about the full extent of its effects on the metabolome and mucosal barrier. To further elucidate this matter, C57BL/6 male mice received drinking water with or without 1% aKG for three weeks, then were subjected to 2.5% dextran sulfate sodium (DSS) induction for 7 days followed by 7 days of recovery. Cecal content and intestinal tissue samples were analyzed for changes in metabolite profile and signaling pathways. Gas chromatography-mass spectrometry (GC-MS) metabolomics revealed a separation between the metabolome of mice treated with or without aKG; putrescine and glycine were significantly increased; and ornithine and amide products, oleamide and urea were significantly decreased. Based on a pathway analysis, aKG treatment induced metabolite changes and enriched glutathione metabolism and the urea cycle. Additionally, signaling pathways committing epithelial cells to the secretory lineage were elevated in aKG-treated mice. Consistently, aKG supplementation increased goblet cells staining, mRNA expression of mucin 2, and, trefoil factor 3 and Krüppel-like factor 4, markers of goblet cell differentiation. These data suggest the ameliorating the effects of aKG against chemically induced colitis involves a reduction in harmful metabolites and the promotion of goblet cell differentiation, resulting in a more-fortified mucus layer.
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Affiliation(s)
- Alejandro Bravo Iniguez
- School of Food Science, Washington State University, Pullman, WA 99164, USA; (A.B.I.); (Q.T.)
| | - Qiyu Tian
- School of Food Science, Washington State University, Pullman, WA 99164, USA; (A.B.I.); (Q.T.)
- Department of Animal Science, Washington State University, Pullman, WA 99164, USA;
| | - Min Du
- Department of Animal Science, Washington State University, Pullman, WA 99164, USA;
| | - Mei-Jun Zhu
- School of Food Science, Washington State University, Pullman, WA 99164, USA; (A.B.I.); (Q.T.)
- Correspondence: ; Tel.: +1-509-335-4016
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25
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Nguyen QV, Chong LC, Hor YY, Lew LC, Rather IA, Choi SB. Role of Probiotics in the Management of COVID-19: A Computational Perspective. Nutrients 2022; 14:274. [PMID: 35057455 PMCID: PMC8781206 DOI: 10.3390/nu14020274] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/06/2022] [Accepted: 01/07/2022] [Indexed: 02/01/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) was declared a pandemic at the beginning of 2020, causing millions of deaths worldwide. Millions of vaccine doses have been administered worldwide; however, outbreaks continue. Probiotics are known to restore a stable gut microbiota by regulating innate and adaptive immunity within the gut, demonstrating the possibility that they may be used to combat COVID-19 because of several pieces of evidence suggesting that COVID-19 has an adverse impact on gut microbiota dysbiosis. Thus, probiotics and their metabolites with known antiviral properties may be used as an adjunctive treatment to combat COVID-19. Several clinical trials have revealed the efficacy of probiotics and their metabolites in treating patients with SARS-CoV-2. However, its molecular mechanism has not been unraveled. The availability of abundant data resources and computational methods has significantly changed research finding molecular insights between probiotics and COVID-19. This review highlights computational approaches involving microbiome-based approaches and ensemble-driven docking approaches, as well as a case study proving the effects of probiotic metabolites on SARS-CoV-2.
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Affiliation(s)
- Quang Vo Nguyen
- Centre for Bioinformatics, School of Data Sciences, Perdana University, Suite 9.2, 9th Floor, Wisma Chase Perdana, Changkat Semantan, Wilayah Persekutuan, Kuala Lumpur 50490, Malaysia;
| | - Li Chuin Chong
- Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Beykoz, Istanbul 34820, Turkey;
| | - Yan-Yan Hor
- Department of Biotechnology, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Gyeongbuk, Korea;
| | - Lee-Ching Lew
- Probionic Corporation, Jeonbuk Institute for Food-Bioindustry, Jeonju 54810, Korea;
| | - Irfan A. Rather
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
- Center of Excellence in Bionanoscience Research, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia
| | - Sy-Bing Choi
- Centre for Bioinformatics, School of Data Sciences, Perdana University, Suite 9.2, 9th Floor, Wisma Chase Perdana, Changkat Semantan, Wilayah Persekutuan, Kuala Lumpur 50490, Malaysia;
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26
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Hu B, Li M, He X, Wang H, Huang JA, Liu Z, Mezzenga R. Flavonoid-Amyloid Fibril Hybrid Hydrogels for Obesity Control via Construction of Gut Microbiota. Biomater Sci 2022; 10:3597-3611. [DOI: 10.1039/d2bm00366j] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Innovative precise clinical approaches to protect humans from the alarming global growth of epidemics of chronic diseases, such as metabolic syndrome (MetS), are urgently needed. Here, we introduce protein hydrogels...
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27
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Kang JW, Zivkovic AM. The Potential Utility of Prebiotics to Modulate Alzheimer's Disease: A Review of the Evidence. Microorganisms 2021; 9:2310. [PMID: 34835436 PMCID: PMC8625457 DOI: 10.3390/microorganisms9112310] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 11/02/2021] [Accepted: 11/02/2021] [Indexed: 12/22/2022] Open
Abstract
The gut microbiome has recently emerged as a critical modulator of brain function, with the so-called gut-brain axis having multiple links with a variety of neurodegenerative and mental health conditions, including Alzheimer's Disease (AD). Various approaches for modulating the gut microbiome toward compositional and functional states that are consistent with improved cognitive health outcomes have been documented, including probiotics and prebiotics. While probiotics are live microorganisms that directly confer beneficial health effects, prebiotics are oligosaccharide and polysaccharide structures that can beneficially modulate the gut microbiome by enhancing the growth, survival, and/or function of gut microbes that in turn have beneficial effects on the human host. In this review, we discuss evidence showing the potential link between gut microbiome composition and AD onset or development, provide an overview of prebiotic types and their roles in altering gut microbial composition, discuss the effectiveness of prebiotics in regulating gut microbiome composition and microbially derived metabolites, and discuss the current evidence linking prebiotics with health outcomes related to AD in both animal models and human trials. Though there is a paucity of human clinical trials demonstrating the effectiveness of prebiotics in altering gut microbiome-mediated health outcomes in AD, current evidence highlights the potential of various prebiotic approaches for beneficially altering the gut microbiota or gut physiology by promoting the production of butyrate, indoles, and secondary bile acid profiles that further regulate gut immunity and mucosal homeostasis, which are associated with beneficial effects on the central immune system and brain functionality.
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Affiliation(s)
| | - Angela M. Zivkovic
- Department of Nutrition, University of California, Davis, CA 95616, USA;
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28
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Daliri EBM, Ofosu FK, Chelliah R, Lee BH, Oh DH. Challenges and Perspective in Integrated Multi-Omics in Gut Microbiota Studies. Biomolecules 2021; 11:300. [PMID: 33671370 PMCID: PMC7922017 DOI: 10.3390/biom11020300] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 02/10/2021] [Accepted: 02/14/2021] [Indexed: 12/14/2022] Open
Abstract
The advent of omic technology has made it possible to identify viable but unculturable micro-organisms in the gut. Therefore, application of multi-omic technologies in gut microbiome studies has become invaluable for unveiling a comprehensive interaction between these commensals in health and disease. Meanwhile, despite the successful identification of many microbial and host-microbial cometabolites that have been reported so far, it remains difficult to clearly identify the origin and function of some proteins and metabolites that are detected in gut samples. However, the application of single omic techniques for studying the gut microbiome comes with its own challenges which may be overcome if a number of different omics techniques are combined. In this review, we discuss our current knowledge about multi-omic techniques, their challenges and future perspective in this field of gut microbiome studies.
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Affiliation(s)
- Eric Banan-Mwine Daliri
- Department of Food Science and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea; (E.B.-M.D.); (F.K.O.); (R.C.)
| | - Fred Kwame Ofosu
- Department of Food Science and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea; (E.B.-M.D.); (F.K.O.); (R.C.)
| | - Ramachandran Chelliah
- Department of Food Science and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea; (E.B.-M.D.); (F.K.O.); (R.C.)
| | - Byong H. Lee
- SportBiomics, Sacramento Inc., California, CA 95660, USA;
| | - Deog-Hwan Oh
- Department of Food Science and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea; (E.B.-M.D.); (F.K.O.); (R.C.)
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29
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Deng F, Zhao BC, Yang X, Lin ZB, Sun QS, Wang YF, Yan ZZ, Liu WF, Li C, Hu JJ, Liu KX. The gut microbiota metabolite capsiate promotes Gpx4 expression by activating TRPV1 to inhibit intestinal ischemia reperfusion-induced ferroptosis. Gut Microbes 2021; 13:1-21. [PMID: 33779497 PMCID: PMC8009132 DOI: 10.1080/19490976.2021.1902719] [Citation(s) in RCA: 147] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 03/02/2021] [Accepted: 03/04/2021] [Indexed: 02/04/2023] Open
Abstract
Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes of gut microbiota and metabolites in intestinal I/R and the role of gut microbiota metabolites on ferroptosis-induced intestinal I/R injury. This study aimed to establish a mouse intestinal I/R model and ileum organoid hypoxia/reoxygenation (H/R) model to explore the changes of the gut microbiota and metabolites during intestinal I/R and protective ability of capsiate (CAT) against ferroptosis-dependent intestinal I/R injury. Intestinal I/R induced disturbance of gut microbiota and significant changes in metabolites. We found that CAT is a metabolite of the gut microbiota and that CAT levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with intestinal I/R injury. Furthermore, CAT reduced ferroptosis-dependent intestinal I/R injury in vivo and in vitro. However, the protective effects of CAT against ferroptosis-dependent intestinal I/R injury were abolished by RSL3, an inhibitor of glutathione peroxidase 4 (Gpx4), which is a negative regulator of ferroptosis. We also found that the ability of CAT to promote Gpx4 expression and inhibit ferroptosis-dependent intestinal I/R injury was abrogated by JNJ-17203212, an antagonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). This study suggests that the gut microbiota metabolite CAT enhances Gpx4 expression and inhibits ferroptosis by activating TRPV1 in intestinal I/R injury, providing a potential avenue for the management of intestinal I/R injury.
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Affiliation(s)
- Fan Deng
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Bing-Cheng Zhao
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiao Yang
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Ze-Bin Lin
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qi-Shun Sun
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yi-Fan Wang
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zheng-Zheng Yan
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Wei-Feng Liu
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Cai Li
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Jing-Juan Hu
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Ke-Xuan Liu
- Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
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30
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Jiang D, He X, Valitutto M, Chen L, Xu Q, Yao Y, Hou R, Wang H. Gut microbiota composition and metabolomic profiles of wild and captive Chinese monals (Lophophorus lhuysii). Front Zool 2020; 17:36. [PMID: 33292307 PMCID: PMC7713318 DOI: 10.1186/s12983-020-00381-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 11/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains in southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolome of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatography (UHPLC) based metabolomics were used to examine the fecal microbiota composition and the metabolomic profile of Chinese monals. RESULTS The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial taxa in the two groups showed remarkable differences at phylum, class, order, and family levels. Metabolomic profiling also revealed differences, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, strong correlations between metabolite types and bacterial genus were detected. CONCLUSIONS There were remarkable differences in the gut microbiota composition and metabolomic profile between wild and captive Chinese monals. This study has established a baseline for a normal gut microbiota and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive organisms have an impact on their overall health and reproduction.
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Affiliation(s)
- Dandan Jiang
- Chengdu Research Base of Giant Panda Breeding, Chengdu, 610081, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu, 610081, China
- Sichuan Academy of Giant Panda, Chengdu, 610081, China
| | - Xin He
- Chengdu Research Base of Giant Panda Breeding, Chengdu, 610081, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu, 610081, China
- Sichuan Academy of Giant Panda, Chengdu, 610081, China
| | - Marc Valitutto
- Chengdu Research Base of Giant Panda Breeding, Chengdu, 610081, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu, 610081, China
- Sichuan Academy of Giant Panda, Chengdu, 610081, China
- EcoHealth Alliance, New York, NY, 10012, USA
| | - Li Chen
- Sichuan Fengtongzhai National Nature reserve administration, Yaan, 625700, China
| | - Qin Xu
- Chengdu Research Base of Giant Panda Breeding, Chengdu, 610081, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu, 610081, China
- Sichuan Academy of Giant Panda, Chengdu, 610081, China
| | - Ying Yao
- Chengdu Research Base of Giant Panda Breeding, Chengdu, 610081, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu, 610081, China
- Sichuan Academy of Giant Panda, Chengdu, 610081, China
| | - Rong Hou
- Chengdu Research Base of Giant Panda Breeding, Chengdu, 610081, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu, 610081, China
- Sichuan Academy of Giant Panda, Chengdu, 610081, China
| | - Hairui Wang
- Chengdu Research Base of Giant Panda Breeding, Chengdu, 610081, China.
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, Chengdu, 610081, China.
- Sichuan Academy of Giant Panda, Chengdu, 610081, China.
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31
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Liu S, Yang Q, Mao J, Bai M, Zhou J, Han X, Mao J. Feedback inhibition of the prephenate dehydratase from Saccharomyces cerevisiae and its mutation in huangjiu (Chinese rice wine) yeast. Lebensm Wiss Technol 2020. [DOI: 10.1016/j.lwt.2020.110040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Li X, Lin Y, Li X, Xu X, Zhao Y, Xu L, Gao Y, Li Y, Tan Y, Qian P, Huang H. Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome. EBioMedicine 2020; 61:103048. [PMID: 33039712 PMCID: PMC7553238 DOI: 10.1016/j.ebiom.2020.103048] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 09/14/2020] [Accepted: 09/15/2020] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment. METHOD Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics. FINDINGS The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group. INTERPRETATION The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment. FUNDING This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).
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Affiliation(s)
- Xiaoqing Li
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, PR China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China
| | - Yu Lin
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, PR China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China
| | - Xue Li
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, PR China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China
| | - Xiaoxiao Xu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, PR China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China
| | - Yanmin Zhao
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, PR China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China
| | - Lin Xu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, PR China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China
| | - Yang Gao
- Department of Hematology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Rd., Hangzhou 310016, Zhejiang, PR China
| | - Yixue Li
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, PR China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China
| | - Yamin Tan
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, PR China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China
| | - Pengxu Qian
- Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Center of Stem Cell and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou 310012, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China.
| | - He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou, Zhejiang, PR China; Institute of Hematology, Zhejiang University, Hangzhou, Zhejiang, PR China; Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, Zhejiang, PR China; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Hangzhou, Zhejiang, PR China.
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Nogacka AM, de Los Reyes-Gavilán CG, Martínez-Faedo C, Ruas-Madiedo P, Suarez A, Mancabelli L, Ventura M, Cifuentes A, León C, Gueimonde M, Salazar N. Impact of Extreme Obesity and Diet-Induced Weight Loss on the Fecal Metabolome and Gut Microbiota. Mol Nutr Food Res 2020; 65:e2000030. [PMID: 32966685 DOI: 10.1002/mnfr.202000030] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
SCOPE A limited number of human studies have characterized fecal microbiota and metabolome in extreme obesity and after diet-induced weight loss. METHODS AND RESULTS Fecal samples from normal-weight and extremely obese adults and from obese participants before and after moderate diet-induced weight loss are evaluated for their interaction with the intestinal adenocarcinoma cell line HT29 using an impedance-based in vitro model, which reveals variations in the interaction between the gut microbiota and host linked to obesity status. Microbiota composition, short chain fatty acids, and other intestinal metabolites are further analyzed to assess the interplay among diet, gut microbiota, and host in extreme obesity. Microbiota profiles are distinct between normal-weight and obese participants and are accompanied by fecal signatures in the metabolism of biliary compounds and catecholamines. Moderate diet-induced weight loss promotes shifts in the gut microbiota, and the primary fecal metabolomics features are associated with diet and the gut-liver and gut-brain axes. CONCLUSIONS Analyses of the fecal microbiota and metabolome enable assessment of the impact of diet on gut microbiota composition and activity, supporting the potential use of certain fecal metabolites or members of the gut microbiota as biomarkers for the efficacy of weight loss in extreme obesity.
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Affiliation(s)
- Alicja M Nogacka
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, 33300, Spain.,Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), Oviedo, 33011, Spain
| | - Clara G de Los Reyes-Gavilán
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, 33300, Spain.,Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), Oviedo, 33011, Spain
| | - Ceferino Martínez-Faedo
- Endocrinology and Nutrition Service, Central University Hospital of Asturias (HUCA), Oviedo, Asturias, 33011, Spain.,Endocrinology, Nutrition, Diabetes and Obesity Group, Institute of Health Research of the Principality of Asturias (ISPA), Oviedo, 33011, Spain
| | - Patricia Ruas-Madiedo
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, 33300, Spain.,Functionality and Ecology of Beneficial Microorganisms, Institute of Health Research of the Principality of Asturias (ISPA), Oviedo, 33011, Spain
| | - Adolfo Suarez
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), Oviedo, 33011, Spain.,Digestive Service, Central University Hospital of Asturias (HUCA), Oviedo, Asturias, 33011, Spain
| | - Leonardo Mancabelli
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, 43121, Italy
| | - Marco Ventura
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, 43121, Italy
| | - Alejandro Cifuentes
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, Madrid, 28049, Spain
| | - Carlos León
- Department of Bioengineering, Universidad Carlos III de Madrid, Leganés, Madrid, Spain
| | - Miguel Gueimonde
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, 33300, Spain.,Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), Oviedo, 33011, Spain
| | - Nuria Salazar
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), Villaviciosa, Asturias, 33300, Spain.,Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), Oviedo, 33011, Spain
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Effects of Maresin 1 (MaR1) on Colonic Inflammation and Gut Dysbiosis in Diet-Induced Obese Mice. Microorganisms 2020; 8:microorganisms8081156. [PMID: 32751593 PMCID: PMC7465372 DOI: 10.3390/microorganisms8081156] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/16/2020] [Accepted: 07/22/2020] [Indexed: 02/06/2023] Open
Abstract
The aim of this study was to characterize the effects of Maresin 1 (MaR1), a DHA-derived pro-resolving lipid mediator, on obesity-related colonic inflammation and gut dysbiosis in diet-induced obese (DIO) mice. In colonic mucosa of DIO mice, the MaR1 treatment decreased the expression of inflammatory genes, such as Tnf-α and Il-1β. As expected, the DIO mice exhibited significant changes in gut microbiota composition at the phylum, genus, and species levels, with a trend to a higher Firmicutes/Bacteroidetes ratio. Deferribacteres and Synergistetes also increased in the DIO animals. In contrast, these animals exhibited a significant decrease in the content of Cyanobacteria and Actinobacteria. Treatment with MaR1 was not able to reverse the dysbiosis caused by obesity on the most abundant phyla. However, the MaR1 treatment increased the content of P. xylanivorans, which have been considered to be a promising probiotic with healthy effects on gut inflammation. Finally, a positive association was found between the Deferribacteres and Il-1β expression, suggesting that the increase in Deferribacteres observed in obesity could contribute to the overexpression of inflammatory cytokines in the colonic mucosa. In conclusion, MaR1 administration ameliorates the inflammatory state in the colonic mucosa and partially compensates changes on gut microbiota caused by obesity.
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Fries-Craft K, Anast JM, Schmitz-Esser S, Bobeck EA. Host immunity and the colon microbiota of mice infected with Citrobacter rodentium are beneficially modulated by lipid-soluble extract from late-cutting alfalfa in the early stages of infection. PLoS One 2020; 15:e0236106. [PMID: 32673362 PMCID: PMC7365448 DOI: 10.1371/journal.pone.0236106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Accepted: 06/29/2020] [Indexed: 11/18/2022] Open
Abstract
Alfalfa is a forage legume commonly associated with ruminant livestock production that may be a potential source of health-promoting phytochemicals. Anecdotal evidence from producers suggests that later cuttings of alfalfa may be more beneficial to non-ruminants; however, published literature varies greatly in measured outcomes, supplement form, and cutting. The objective of this study was to measure body weight, average daily feed intake, host immunity, and the colon microbiota composition in mice fed hay, aqueous, and chloroform extracts of early (1st) and late (5th) cutting alfalfa before and after challenge with Citrobacter rodentium. Prior to inoculation, alfalfa supplementation did not have a significant impact on body weight or feed intake, but 5th cutting alfalfa was shown to improve body weight at 5- and 6-days post-infection compared to 1st cutting alfalfa (P = 0.02 and 0.01). Combined with the observation that both chloroform extracts improved mouse body weight compared to control diets in later stages of C. rodentium infection led to detailed analyses of the immune system and colon microbiota in mice fed 1st and 5th cutting chloroform extracts. Immediately following inoculation, 5th cutting chloroform extracts significantly reduced the relative abundance of C. rodentium (P = 0.02) and did not display the early lymphocyte recruitment observed in 1st cutting extract. In later timepoints, both chloroform extracts maintained lower splenic B-cell and macrophage populations while increasing the relative abundance of potentially beneficially genera such as Turicibacter (P = 0.02). At 21dpi, only 5th cutting chloroform extracts increased the relative abundance of beneficial Akkermansia compared to the control diet (P = 0.02). These results suggest that lipid soluble compounds enriched in late-cutting alfalfa modulate pathogen colonization and early immune responses to Citrobacter rodentium, contributing to protective effects on body weight.
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Affiliation(s)
- K. Fries-Craft
- Department of Animal Science, Iowa State University, Ames, Iowa, United States of America
| | - J. M. Anast
- Department of Animal Science, Iowa State University, Ames, Iowa, United States of America
- Interdepartmental Microbiology Graduate Program, Iowa State University, Ames, Iowa, United States of America
| | - S. Schmitz-Esser
- Department of Animal Science, Iowa State University, Ames, Iowa, United States of America
- Interdepartmental Microbiology Graduate Program, Iowa State University, Ames, Iowa, United States of America
| | - E. A. Bobeck
- Department of Animal Science, Iowa State University, Ames, Iowa, United States of America
- * E-mail:
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Singh V, Galla S, Golonka RM, Patterson AD, Chassaing B, Joe B, Vijay-Kumar M. Lipocalin 2 deficiency-induced gut microbiota dysbiosis evokes metabolic syndrome in aged mice. Physiol Genomics 2020; 52:314-321. [PMID: 32628083 DOI: 10.1152/physiolgenomics.00118.2019] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Lipocalin 2 (Lcn2) is a multifunctional innate immune protein that limits microbial overgrowth. Our previous study demonstrated that the gut microbiota directly induces intestinal Lcn2 production, and Lcn2-deficient (Lcn2-/-) mice exhibit gut dysbiosis. Coincidentally, gut dysbiosis is associated with metabolic syndrome pathogenesis, and elevated Lcn2 levels has been considered a potential clinical biomarker of metabolic syndrome. Yet whether Lcn2 mitigates or exacerbates metabolic syndrome remains inconclusive. Our objective was to determine whether Lcn2 deficiency-induced compositional changes in gut microbiota contribute to gain in adiposity in aged mice. Utilizing Lcn2-/- mice and their wild-type (WT) littermates, we measured metabolic markers, including fasting blood glucose, serum lipids, fat pad weight, and insulin resistance at ages 3, 6, and 9 mo old. Relative to WT mice, aged Lcn2-/- mice exhibited a gain in adiposity associated with numerous features of metabolic syndrome, including insulin resistance and dyslipidemia. Surprisingly, supplementation with a high-fat diet did not further aggravate metabolic syndrome that spontaneously occurs in Lcn2-/- mice by 6 mo of age. Interestingly, chow-fed Lcn2-/- mice displayed marked differences in the bacterial abundance and metabolomic profile of the gut microbiota compared with WT mice. Overall, our results demonstrate that Lcn2 is essential to maintain metabolic and gut microbiotal homeostasis, where deficiency induces spontaneous delayed onset of metabolic syndrome.
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Affiliation(s)
- Vishal Singh
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania
| | - Sarah Galla
- Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio
| | - Rachel M Golonka
- Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio
| | - Andrew D Patterson
- Department of Veterinary and Biomedical Sciences, Pennsylvania State University, State College, Pennsylvania
| | - Benoit Chassaing
- Neuroscience Institute, Georgia State University, Atlanta, Georgia.,Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia
| | - Bina Joe
- Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio
| | - Matam Vijay-Kumar
- Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio
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Pan Y, Wan X, Zeng F, Zhong R, Guo W, Lv XC, Zhao C, Liu B. Regulatory effect of Grifola frondosa extract rich in polysaccharides and organic acids on glycolipid metabolism and gut microbiota in rats. Int J Biol Macromol 2020; 155:1030-1039. [DOI: 10.1016/j.ijbiomac.2019.11.067] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2019] [Revised: 10/25/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023]
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38
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Hong Y, Li B, Zheng N, Wu G, Ma J, Tao X, Chen L, Zhong J, Sheng L, Li H. Integrated Metagenomic and Metabolomic Analyses of the Effect of Astragalus Polysaccharides on Alleviating High-Fat Diet-Induced Metabolic Disorders. Front Pharmacol 2020; 11:833. [PMID: 32587515 PMCID: PMC7299173 DOI: 10.3389/fphar.2020.00833] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 05/20/2020] [Indexed: 12/31/2022] Open
Abstract
Most herbal polysaccharides possess multiple benefits against metabolic disorders, such as non-alcoholic fatty liver disease (NAFLD) and obesity. However, the underlying mechanisms are largely unknown. Here, male C57BL/6J mice were fed with chow or high-fat diet (HFD) with or without Astragalus polysaccharides (APS) supplementation, and gut microbial profile and metabolite profile were studied by metagenomic sequencing and untargeted metabolomics, respectively. APS was effective in alleviating HFD-induced metabolic disorders, with the alteration of gut microbiota composition and function. A total of 188 species, which mainly from Bacteroidetes, Actinobacteria, Firmicutes, and Proteobacteria phyla, and 36 metabolites were markedly changed by HFD and revered by APS. Additionally, the altered glutathione metabolism and purine metabolism pathways were identified by both metagenomic function analysis and metabolite pathway enrichment analysis. Furthermore, the gut microbial alteration was associated with the changes of key intestinal metabolites. We found 31 and 20 species were correlated with purine metabolism and glutathione metabolism, respectively. Together, our results showed significant metagenomic and metabolomic changes after HFD feeding and APS intervention, revealed the potential correlation between gut microbial species and metabolites, and highlighted mechanisms of herb-derived polysaccharides by modulating gut microbiome and host metabolism underlying their benefits on metabolic disorders.
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Affiliation(s)
- Ying Hong
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Bingbing Li
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ningning Zheng
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Gaosong Wu
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Junli Ma
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xin Tao
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Linlin Chen
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jing Zhong
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.,Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Affiliated Cent Hospital Huzhou University, Huzhou, China
| | - Lili Sheng
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Houkai Li
- Functional Metabolomic and Gut Microbiome Laboratory, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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39
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Lundberg R, Toft MF, Metzdorff SB, Hansen CHF, Licht TR, Bahl MI, Hansen AK. Human microbiota-transplanted C57BL/6 mice and offspring display reduced establishment of key bacteria and reduced immune stimulation compared to mouse microbiota-transplantation. Sci Rep 2020; 10:7805. [PMID: 32385373 PMCID: PMC7211022 DOI: 10.1038/s41598-020-64703-z] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 04/20/2020] [Indexed: 02/07/2023] Open
Abstract
Transplantation of germ-free (GF) mice with microbiota from mice or humans stimulates the intestinal immune system in disparate ways. We transplanted a human microbiota into GF C57BL/6 mice and a murine C57BL/6 microbiota into GF C57BL/6 mice and Swiss-Webster (SW) mice. Mice were bred to produce an offspring generation. 56% of the Operational Taxonomic Units (OTUs) present in the human donor microbiota established in the recipient mice, whereas 81% of the C57BL/6 OTUs established in the recipient C57BL/6 and SW mice. Anti-inflammatory bacteria such as Faecalibacterium and Bifidobacterium from humans were not transferred to mice. Expression of immune-related intestinal genes was lower in human microbiota-mice and not different between parent and offspring generation. Expression of intestinal barrier-related genes was slightly higher in human microbiota-mice. Cytokines and chemokines measured in plasma were differentially present in human and mouse microbiota-mice. Minor differences in microbiota and gene expression were found between transplanted mice of different genetics. It is concluded that important immune-regulating bacteria are lost when transplanting microbiota from humans to C57BL/6 mice, and that the established human microbiota is a weak stimulator of the murine immune system. The results are important for study design considerations in microbiota transplantation studies involving immunological parameters.
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Affiliation(s)
- Randi Lundberg
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1871, Frederiksberg C, Denmark.
- Internal Research and Development, Taconic Biosciences, 4623, Lille Skensved, Denmark.
- Chr. Hansen, 2970, Hoersholm, Denmark.
| | - Martin F Toft
- Internal Research and Development, Taconic Biosciences, 4623, Lille Skensved, Denmark
- QM Diagnostics, 6534, AT Nijmegen, The Netherlands
| | - Stine B Metzdorff
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1871, Frederiksberg C, Denmark
| | - Camilla H F Hansen
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1871, Frederiksberg C, Denmark
| | - Tine R Licht
- National Food Institute, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
| | - Martin I Bahl
- National Food Institute, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark
| | - Axel K Hansen
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1871, Frederiksberg C, Denmark
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40
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Sanada S, Suzuki T, Nagata A, Hashidume T, Yoshikawa Y, Miyoshi N. Intestinal microbial metabolite stercobilin involvement in the chronic inflammation of ob/ob mice. Sci Rep 2020; 10:6479. [PMID: 32296105 PMCID: PMC7160104 DOI: 10.1038/s41598-020-63627-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 03/30/2020] [Indexed: 12/26/2022] Open
Abstract
It is crucial that the host and intestinal microflora interact and influence each other to maintain homeostasis and trigger pathological processes. Recent studies have shown that transplantation of the murine intestinal content to recipient germ-free mice enables transmission of the donor’s phenotypes, such as low level chronic inflammation associated with lifestyle-related diseases. These findings indicate that intestinal bacteria produce some molecules to trigger pathological signals. However, fecal microbial metabolites that induce obesity and the type II diabetic phenotype have not been fully clarified. Here, we showed that the intestinal bacterial metabolite stercobilin, a pigment of feces, induced proinflammatory activities including TNF-α and IL-1β induction in mouse macrophage RAW264 cells. Proinflammatory stercobilin levels were significantly higher in ob/ob mice feces than in the feces of control C57BL/6 J mice. Moreover, in this study, we detected stercobilin in mice plasma for the first time, and the levels were higher in ob/ob mice than that of C57BL/6 J mice. Therefore, stercobilin is potentially reabsorbed, circulated through the blood system, and contributes to low level chronic inflammation in ob/ob mice. Since, stercobilin is a bioactive metabolite, it could be a potentially promising biomarker for diagnosis. Further analyses to elucidate the metabolic rate and the reabsorption mechanism of stercobilin may provide possible therapeutic and preventive targets.
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Affiliation(s)
- Shunsuke Sanada
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan
| | - Takuji Suzuki
- Food Environmental Design Course, Faculty of Education, Art and Science, Yamagata University, Yamagata, Japan
| | - Akika Nagata
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan
| | - Tsutomu Hashidume
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan
| | - Yuko Yoshikawa
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.,School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Tokyo, Japan
| | - Noriyuki Miyoshi
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.
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41
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Witting M, Böcker S. Current status of retention time prediction in metabolite identification. J Sep Sci 2020; 43:1746-1754. [DOI: 10.1002/jssc.202000060] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2020] [Revised: 03/04/2020] [Accepted: 03/04/2020] [Indexed: 12/23/2022]
Affiliation(s)
- Michael Witting
- Research Unit Analytical BioGeoChemistryHelmholtz Zentrum München Neuherberg Germany
- Chair of Analytical Food ChemistryTUM School of Life Sciences, Technische Universität München Freising Germany
| | - Sebastian Böcker
- Chair of BioinformaticsFriedrich‐Schiller‐Universität Jena Jena Germany
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42
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Eetemadi A, Rai N, Pereira BMP, Kim M, Schmitz H, Tagkopoulos I. The Computational Diet: A Review of Computational Methods Across Diet, Microbiome, and Health. Front Microbiol 2020; 11:393. [PMID: 32318028 PMCID: PMC7146706 DOI: 10.3389/fmicb.2020.00393] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 02/26/2020] [Indexed: 12/12/2022] Open
Abstract
Food and human health are inextricably linked. As such, revolutionary impacts on health have been derived from advances in the production and distribution of food relating to food safety and fortification with micronutrients. During the past two decades, it has become apparent that the human microbiome has the potential to modulate health, including in ways that may be related to diet and the composition of specific foods. Despite the excitement and potential surrounding this area, the complexity of the gut microbiome, the chemical composition of food, and their interplay in situ remains a daunting task to fully understand. However, recent advances in high-throughput sequencing, metabolomics profiling, compositional analysis of food, and the emergence of electronic health records provide new sources of data that can contribute to addressing this challenge. Computational science will play an essential role in this effort as it will provide the foundation to integrate these data layers and derive insights capable of revealing and understanding the complex interactions between diet, gut microbiome, and health. Here, we review the current knowledge on diet-health-gut microbiota, relevant data sources, bioinformatics tools, machine learning capabilities, as well as the intellectual property and legislative regulatory landscape. We provide guidance on employing machine learning and data analytics, identify gaps in current methods, and describe new scenarios to be unlocked in the next few years in the context of current knowledge.
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Affiliation(s)
- Ameen Eetemadi
- Department of Computer Science, University of California, Davis, Davis, CA, United States
- Genome Center, University of California, Davis, Davis, CA, United States
| | - Navneet Rai
- Genome Center, University of California, Davis, Davis, CA, United States
| | - Beatriz Merchel Piovesan Pereira
- Genome Center, University of California, Davis, Davis, CA, United States
- Department of Microbiology, University of California, Davis, Davis, CA, United States
| | - Minseung Kim
- Department of Computer Science, University of California, Davis, Davis, CA, United States
- Genome Center, University of California, Davis, Davis, CA, United States
- Process Integration and Predictive Analytics (PIPA LLC), Davis, CA, United States
| | - Harold Schmitz
- Graduate School of Management, University of California, Davis, Davis, CA, United States
| | - Ilias Tagkopoulos
- Department of Computer Science, University of California, Davis, Davis, CA, United States
- Genome Center, University of California, Davis, Davis, CA, United States
- Process Integration and Predictive Analytics (PIPA LLC), Davis, CA, United States
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43
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Schulfer A, Santiago-Rodriguez TM, Ly M, Borin JM, Chopyk J, Blaser MJ, Pride DT. Fecal Viral Community Responses to High-Fat Diet in Mice. mSphere 2020; 5:e00833-19. [PMID: 32102942 PMCID: PMC7045389 DOI: 10.1128/msphere.00833-19] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 02/05/2020] [Indexed: 12/22/2022] Open
Abstract
Alterations in diet can have significant impact on the host, with high-fat diet (HFD) leading to obesity, diabetes, and inflammation of the gut. Although membership and abundances in gut bacterial communities are strongly influenced by diet, substantially less is known about how viral communities respond to dietary changes. Examining fecal contents of mice as the mice were transitioned from normal chow to HFD, we found significant changes in the relative abundances and the diversity in the gut of bacteria and their viruses. Alpha diversity of the bacterial community was significantly diminished in response to the diet change but did not change significantly in the viral community. However, the diet shift significantly impacted the beta diversity in both the bacterial and viral communities. There was a significant shift away from the relatively abundant Siphoviridae accompanied by increases in bacteriophages from the Microviridae family. The proportion of identified bacteriophage structural genes significantly decreased after the transition to HFD, with a conserved loss of integrase genes in all four experimental groups. In total, this study provides evidence for substantial changes in the intestinal virome disproportionate to bacterial changes, and with alterations in putative viral lifestyles related to chromosomal integration as a result of shift to HFD.IMPORTANCE Prior studies have shown that high-fat diet (HFD) can have profound effects on the gastrointestinal (GI) tract microbiome and also demonstrate that bacteria in the GI tract can affect metabolism and lean/obese phenotypes. We investigated whether the composition of viral communities that also inhabit the GI tract are affected by shifts from normal to HFD. We found significant and reproducible shifts in the content of GI tract viromes after the transition to HFD. The differences observed in virome community membership and their associated gene content suggest that these altered viral communities are populated by viruses that are more virulent toward their host bacteria. Because HFD also are associated with significant shifts in GI tract bacterial communities, we believe that the shifts in the viral community may serve to drive the changes that occur in associated bacterial communities.
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Affiliation(s)
| | | | - Melissa Ly
- Department of Pathology, University of California, San Diego, California, USA
| | - Joshua M Borin
- Division of Biological Sciences, University of California, San Diego, California, USA
| | - Jessica Chopyk
- Department of Pathology, University of California, San Diego, California, USA
| | - Martin J Blaser
- New York University, New York, New York, USA
- Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey, USA
| | - David T Pride
- Department of Pathology, University of California, San Diego, California, USA
- Department of Medicine, University of California, San Diego, California, USA
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44
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Misra BB. The Connection and Disconnection Between Microbiome and Metabolome: A Critical Appraisal in Clinical Research. Biol Res Nurs 2020; 22:561-576. [PMID: 32013533 DOI: 10.1177/1099800420903083] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Big data-driven omics research has led to a steep rise in investigations involving two of the most functional omes, the metabolome and microbiome. The former is touted as the closest to the phenotype, and the latter is implicated in general well-being and a plethora of human diseases. Although some research publications have integrated the concepts of the two domains, most focus their analyses on evidence solely originating from one or the other. With a growing interest in connecting the microbiome and metabolome in the context of disease, researchers must also appreciate the disconnect between the two domains. In the present review, drawing examples from the current literature, tools, and resources, I discuss the connections between the microbiome and metabolome and highlight challenges and opportunities in linking them together for the basic, translational, clinical, and nursing research communities.
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Affiliation(s)
- Biswapriya B Misra
- Center for Precision Medicine, Department of Internal Medicine, Section of Molecular Medicine, 12279Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA
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45
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Cao W, Chin Y, Chen X, Mi Y, Xue C, Wang Y, Tang Q. The role of gut microbiota in the resistance to obesity in mice fed a high fat diet. Int J Food Sci Nutr 2019; 71:453-463. [PMID: 31774018 DOI: 10.1080/09637486.2019.1686608] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The prevalence of diet induced obesity (DIO) is a huge threat to global health. Differences in gut microbiota may be concerned with DIO. Sixty male C57BL/6J mice were fed with high fat diet (HFD, 45% kcal from fat) for 16 weeks. Among them, body weight, body fat rate and the lipid content in plasma or liver of six mice (Lean (L) group) were obviously lower than average levels (Fatty (F) group). These results supported that some individuals were resistant to HFD induced obesity. Using 16S rRNA analysis to investigate the role of gut microbiota in this resistance, we found several alterations associated with the resistance, such as an increase of Muribaculaceae in L group. Moreover, analysis of predicted microbial function suggested that bacteria in F group could better utilise HFD compared to L group. In conclusion, gut microbiota might play a bigger role than diet in resisting obesity, and it could be a potential target for obesity treatment.
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Affiliation(s)
- Wanxiu Cao
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Yaoxian Chin
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Xin Chen
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Ye Mi
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Changhu Xue
- College of Food Science and Engineering, Ocean University of China, Qingdao, China.,Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China
| | - Yuming Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
| | - Qingjuan Tang
- College of Food Science and Engineering, Ocean University of China, Qingdao, China
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46
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Lv Y, Pan J, Huo T, Zhao Y, Liu S. Enhanced microbial metabolism in one stage partial nitritation-anammox system treating low strength wastewater by novel composite carrier. WATER RESEARCH 2019; 163:114872. [PMID: 31362210 DOI: 10.1016/j.watres.2019.114872] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 07/09/2019] [Accepted: 07/14/2019] [Indexed: 06/10/2023]
Abstract
One stage partial nitritation-anammox (PN-A) process has attracted more and more attention due to the low investment cost but the instability in treating low strength wastewater. In this study, for producing a novel composite carrier that could provide high ammonia microenvironment in low strength wastewater, the zeolites and floating materials were combined in the spherical shell and distributed evenly by the spherical polyhedron. And a moving bed biofilm reactor (MBBR) with the composite carriers and ordinary carriers without zeolites as control group was operated for nearly 120 days. The PN-A process were realized in 53 days, and the total nitrogen removal efficiency reached around 85% at influent ammonium concentration of 50 mg/L finally. Analysis of 16S rRNA gene sequencing revealed that the composite carriers showed significant promotion on the proliferation of ammonium oxidizing bacteria (AOB) and enrichment of anaerobic ammonium oxidizing bacteria (AnAOB), accounting for 19.14% and 41.65% on the surface, respectively. Moreover, the existence of relative higher abundance of ammonia on the composite carrier surface was validated by the metabolite biomarker of glutamate and especially spermidine. The metabolomics analysis and 16S rRNA function prediction showed that the protein synthesis pathway was obviously upregulated on the composite carriers surface compared with that on the ordinary carriers surface. The higher abundance of glutamate and putrescine indicated that the composite carrier could stimulate the metabolism and growth of bacteria. The present study provided a functional carrier to realize the transformation of activated sludge system into PN-A system treating low strength wastewater, which is significant to the application of the process in mainstream.
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Affiliation(s)
- Yufeng Lv
- Department of Environmental Engineering, Peking University, Beijing, 100871, China; Key Laboratory of Water and Sediment Sciences, Ministry of Education of China, Beijing, 100871, China
| | - Juejun Pan
- Department of Environmental Engineering, Peking University, Beijing, 100871, China; Key Laboratory of Water and Sediment Sciences, Ministry of Education of China, Beijing, 100871, China
| | - Tangran Huo
- Department of Environmental Engineering, Peking University, Beijing, 100871, China; Key Laboratory of Water and Sediment Sciences, Ministry of Education of China, Beijing, 100871, China
| | - Yunpeng Zhao
- Department of Environmental Engineering, Peking University, Beijing, 100871, China; Key Laboratory of Water and Sediment Sciences, Ministry of Education of China, Beijing, 100871, China
| | - Sitong Liu
- Department of Environmental Engineering, Peking University, Beijing, 100871, China; Key Laboratory of Water and Sediment Sciences, Ministry of Education of China, Beijing, 100871, China.
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47
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A Unified Conceptual Framework for Metabolic Phenotyping in Diagnosis and Prognosis. Trends Pharmacol Sci 2019; 40:763-773. [PMID: 31511194 DOI: 10.1016/j.tips.2019.08.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 07/31/2019] [Accepted: 08/11/2019] [Indexed: 12/15/2022]
Abstract
Understanding metabotype (multicomponent metabolic characteristics) variation can help to generate new diagnostic and prognostic biomarkers, as well as models, with potential to impact on patient management. We present a suite of conceptual approaches for the generation, analysis, and understanding of metabotypes from body fluids and tissues. We describe and exemplify four fundamental approaches to the generation and utilization of metabotype data via multiparametric measurement of (i) metabolite levels, (ii) metabolic trajectories, (iii) metabolic entropies, and (iv) metabolic networks and correlations in space and time. This conceptual framework can underpin metabotyping in the scenario of personalized medicine, with the aim of improving clinical outcomes for patients, but the framework will have value and utility in areas of metabolic profiling well beyond this exemplar.
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48
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Gual-Grau A, Guirro M, Mayneris-Perxachs J, Arola L, Boqué N. Impact of different hypercaloric diets on obesity features in rats: a metagenomics and metabolomics integrative approach. J Nutr Biochem 2019; 71:122-131. [DOI: 10.1016/j.jnutbio.2019.06.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 05/14/2019] [Accepted: 06/06/2019] [Indexed: 02/07/2023]
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49
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Sarmiento MRA, de Paula TO, Borges FM, Ferreira-Machado AB, Resende JA, Moreira APB, Dutra Luquetti SCP, Cesar DE, da Silva VL, Diniz CG. Obesity, Xenobiotic Intake and Antimicrobial-Resistance Genes in the Human Gastrointestinal Tract: A Comparative Study of Eutrophic, Overweight and Obese Individuals. Genes (Basel) 2019; 10:genes10050349. [PMID: 31067837 PMCID: PMC6562451 DOI: 10.3390/genes10050349] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 04/29/2019] [Accepted: 04/30/2019] [Indexed: 01/16/2023] Open
Abstract
Although lifestyle and physiology in obese individuals are accepted to lead to changes in the intestinal microbiota, uncertainty remains about microbiota dysbiosis, and xenobiotics intake, as a source of selective pressure, independent of antimicrobial chemotherapy. The aim of this study was to compare the occurrence of antimicrobial resistance genetic markers (ARG) in faecal specimens of eutrophic, overweight and obese individuals, and their correlation with xenobiotic intake and gut bacteria density. Methods: This was a cross-sectional case-controlled study including 72 adult participants with no record of intestinal or systemic diseases, or recent use of antimicrobials, grouped as eutrophic, overweight, or obese. Anthropometric profile, eating habits and oral xenobiotics intake were recorded. Faecal metagenomic DNA was used to screen for ARG by PCR, and to measure bacterial groups by fluorescence in situ hybridization (FISH). Student’s t and Wilcoxon tests were used to compare means and differences in ARG detection (95% confidence intervals). Correlation analyses (odds ratio) and relationships between bacteria density and ARG were determined. Results: Increase in abdominal circumference, waist circumference, hip, waist-hip ratio, BMI, carbohydrate, fibres, and total calorie intakes were different from eutrophic to obese participants. Habitual use of antihypertensive and anti-inflammatory drugs, antacids, and artificial sweeteners were associated mainly with obesity and overweight. Nutritional supplements were associated to the eutrophic group. ARG screening showed differences being more frequent among obese, and positive for 27 genetic markers related to β-lactams, tetracyclines, the macrolide lincosamide and streptogramin group, quinolones, sulfonamides, aminoglycosides, and efflux pump. Positive correlation between ARG and BMI, caloric intake, and intake of xenobiotics, was observed for obese individuals. Relationships among ARG detection and bacteria densities were also different. Conclusions: This study reinforces the hypothesis that obese individuals may harbour an altered gut microbiota, if compared to eutrophic. The overweight individuals display a transitional gut microbiota which seems to be between eutrophic and obese. Furthermore, the increased xenobiotic intake associated to obesity may play an important role in the antimicrobial resistance phenomenon.
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Affiliation(s)
- Marjorie Raquel Anariba Sarmiento
- Laboratory of Bacterial Physiology and Molecular Genetics, Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, 36036-330 Juiz de Fora, MG, Brazil.
| | - Thais Oliveira de Paula
- Laboratory of Bacterial Physiology and Molecular Genetics, Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, 36036-330 Juiz de Fora, MG, Brazil.
| | - Francis Moreira Borges
- Laboratory of Bacterial Physiology and Molecular Genetics, Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, 36036-330 Juiz de Fora, MG, Brazil.
| | - Alessandra Barbosa Ferreira-Machado
- Laboratory of Bacterial Physiology and Molecular Genetics, Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, 36036-330 Juiz de Fora, MG, Brazil.
| | - Juliana Alves Resende
- Department of Pharmacy and Nutrition, Federal University of Espirito Santo, 29500-000 Alegre, ES, Brasil.
| | - Ana Paula Boroni Moreira
- Department of Nutrition, Federal University of Juiz de Fora, 36036-330 Juiz de Fora, MG, Brazil.
| | | | | | - Vânia Lúcia da Silva
- Laboratory of Bacterial Physiology and Molecular Genetics, Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, 36036-330 Juiz de Fora, MG, Brazil.
| | - Claudio Galuppo Diniz
- Laboratory of Bacterial Physiology and Molecular Genetics, Department of Parasitology, Microbiology and Immunology, Federal University of Juiz de Fora, 36036-330 Juiz de Fora, MG, Brazil.
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50
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Chetwynd AJ, Ogilvie LA, Nzakizwanayo J, Pazdirek F, Hoch J, Dedi C, Gilbert D, Abdul-Sada A, Jones BV, Hill EM. The potential of nanoflow liquid chromatography-nano electrospray ionisation-mass spectrometry for global profiling the faecal metabolome. J Chromatogr A 2019; 1600:127-136. [PMID: 31047664 DOI: 10.1016/j.chroma.2019.04.028] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 04/01/2019] [Accepted: 04/11/2019] [Indexed: 01/03/2023]
Abstract
Faeces are comprised of a wide array of metabolites arising from the circulatory system as well as the human microbiome. A global metabolite analysis (metabolomics) of faecal extracts offers the potential to uncover new compounds which may be indicative of the onset of bowel diseases such as colorectal cancer (CRC). To date, faecal metabolomics is still in its infancy and the compounds of low abundance present in faecal extracts poorly characterised. In this study, extracts of faeces from healthy subjects were profiled using a sensitive nanoflow-nanospray LC-MS platform which resulted in highly repeatable peak retention times (<2% CV) and intensities (<15% CV). Analysis of the extracts revealed wide coverage of the faecal metabolome including detection of low abundant signalling compounds such as sex steroids and eicosanoids, alongside highly abundant pharmaceuticals and tetrapyrrole metabolites. A small pilot study investigating differences in metabolomics profiles of faecal samples obtained from 7 CRC, 25 adenomatous polyp and 26 healthy groups revealed that secondary bile acids, conjugated androgens, eicosanoids, phospholipids and an unidentified haem metabolite were potential classes of metabolites that discriminated between the CRC and control sample groups. However, much larger follow up studies are needed to confirm which components of the faecal metabolome are associated with actual CRC disease rather than dietary influences. This study reveals the potential of nanospray-nanoflow LC-MS profiling of faecal samples from large scale cohort studies for uncovering the role of the faecal metabolome in colorectal disease formation.
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Affiliation(s)
- Andrew J Chetwynd
- School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK; School of Geography, Earth and Environmental Sciences, University of Birmingham, Edgbaston, B15 2TT, UK
| | - Lesley A Ogilvie
- School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK
| | - Jonathan Nzakizwanayo
- School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK
| | - Filip Pazdirek
- Surgery Department, 2nd Medical Faculty of Charles University and University Hospital Motol, Prague, Czech Republic
| | - Jiří Hoch
- Surgery Department, 2nd Medical Faculty of Charles University and University Hospital Motol, Prague, Czech Republic
| | - Cinzia Dedi
- School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK
| | - Duncan Gilbert
- Sussex Cancer Centre, Royal Sussex County Hospital, Brighton, BN2 5DA, UK
| | - Alaa Abdul-Sada
- School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK
| | - Brian V Jones
- School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton, BN2 4GJ, UK; Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK
| | - Elizabeth M Hill
- School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK.
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