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Xiong L, Huang YX, Mao L, Xu Y, Deng YQ. Targeting gut microbiota and its associated metabolites as a potential strategy for promoting would healing in diabetes. World J Diabetes 2025; 16:98788. [DOI: 10.4239/wjd.v16.i5.98788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 01/03/2025] [Accepted: 03/05/2025] [Indexed: 04/25/2025] Open
Abstract
Impaired healing of diabetic wounds is one of the most important complications of diabetes, often leading to lower limb amputations and incurring significant economic and psychosocial costs. Unfortunately, there are currently no effective prevention or treatment strategies available. Recent research has reported that an imbalance in the gut microbiota, known as dysbiosis, was linked to the onset of type 2 diabetes, as well as the development and progression of diabetic complications. Indeed, the gut microbiota has emerged as a promising therapeutic approach for treating type 2 diabetes and related diseases. However, there is few of literatures specifically discussing the relationship between gut microbiota and diabetic wounds. This review aims to explore the potential role of the gut microbiota, especially probiotics, and its associated byproducts such as short chain fatty acids, bile acids, hydrogen sulfide, and tryptophan metabolites on wound healing to provide fresh insights and novel perspectives for the treatment of chronic wounds in diabetes.
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Affiliation(s)
- Ling Xiong
- Department of Dermatology & STD, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Ya-Xin Huang
- Department of Dermatology & STD, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Lan Mao
- Department of Dermatology & STD, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Yong Xu
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Yong-Qiong Deng
- Department of Dermatology & STD, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu 610000, Sichuan Province, China
- Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, Sichuan Province, China
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Wang X, Ding Y, Zhang X, Feng Y, Li C, Ge Y, Yang Y, Su J, Chu X. The effects of degraded polysaccharides from Acanthopanax senticosus on growth, antioxidant and immune effects in broiler chicks based on intestinal flora. Poult Sci 2025; 104:104933. [PMID: 40010047 PMCID: PMC11910097 DOI: 10.1016/j.psj.2025.104933] [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: 12/11/2024] [Revised: 02/15/2025] [Accepted: 02/19/2025] [Indexed: 02/28/2025] Open
Abstract
The aim of this study was to evaluate the effect of degraded polysaccharide of Acanthopanax senticosus (ASPS-1) on the immunological effects and appropriate dosage of broiler chicks with a view to developing a new feed additive. For the experimental design, 180 broiler chicks were randomly divided into six groups, ASPS-1 low, medium and high dose groups, undegraded Acanthopanax senticosus polysaccharide (ASPS) low and medium dose groups and blank control group. The drug was administered for 21 consecutive days, and the growth and data of immune organ index and immune factors were recorded on the 7th, 14th and 21st d. Finally, the effect of ASPS-1 on the intestinal flora of broiler chicks was investigated by high-throughput sequencing of the 16S rRNA gene and the correlation between the main flora and intestinal indexes was analyzed, and the function of microbial community was predicted by using PICRUSt2. The results showed that the addition of high dose of ASPS-1 could promote the body weight growth of broiler chicks, had no significant effect on immune organs, significantly promoted the increase of intestinal villi and crypt ratio, and effectively regulated the levels of serum antioxidant factors and immune indexes. Analysis of the intestinal flora showed that ASPS-1H promoted the proliferation of Lactobacillus, Faecalibacterium, Negativibacillus, and Eubacterium and inhibited the colonization of Desulfovibrio and Turicibacter, and that proliferation of Faecalibacterium, Negativibacillus and Eubacterium was associated with the development of intestinal villi. Predictive analysis of PICRUSt2 function indicates that proliferation of Lactobacillus, Faecalibacterium, Negativibacillus and Eubacterium functions through amino acid metabolism, global and overview maps, replication and repair pathways function. In summary, the addition of high doses of ASPS-1 can improve the immunity of broilers and has the potential to be used as a feed additive.
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Affiliation(s)
- Xueyan Wang
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Yi Ding
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Xueping Zhang
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Yichao Feng
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Chenglin Li
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Yichen Ge
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Yaosen Yang
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Jianqing Su
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China
| | - Xiuling Chu
- College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China.
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Mallardi D, Chimienti G, Maqoud F, Orlando A, Drago S, Malerba E, De Virgilio C, Akbarali HI, Russo F. The Dual Role of Exogenous Hydrogen Sulfide (H 2S) in Intestinal Barrier Mitochondrial Function: Insights into Cytoprotection and Cytotoxicity Under Non-Stressed Conditions. Antioxidants (Basel) 2025; 14:384. [PMID: 40298652 PMCID: PMC12024010 DOI: 10.3390/antiox14040384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 03/19/2025] [Accepted: 03/20/2025] [Indexed: 04/30/2025] Open
Abstract
Hydrogen sulfide (H2S) is a critical gasotransmitter that plays a dual role in physiological and pathological processes, particularly in the gastrointestinal tract. While physiological levels of H2S exert cytoprotective effects, excessive concentrations can lead to toxicity, oxidative stress, and inflammation. The aim of this study was to investigate the dose-dependent effects of exogenous H2S on mitochondrial functions and biogenesis in intestinal epithelial cells under non-stressed conditions. Using a Caco-2 monolayer model, we evaluated the impact of sodium hydrosulfide (NaHS) at concentrations ranging from 1 × 10-7 M to 5 × 10-3 M on mitochondrial metabolism, redox balance, antioxidant defense, inflammatory responses, autophagy/mitophagy, and apoptosis. Our results demonstrated a biphasic response: low-to-moderate H2S concentrations (1 × 10-7 M-1.5 × 10-3 M) enhance mitochondrial biogenesis through PGC-1α activation, upregulating TFAM and COX-4 expression, and increasing the mtDNA copy number. In contrast, higher concentrations (2 × 10-3-5 × 10-3 M) impair mitochondrial function, induce oxidative stress, and promote apoptosis. These effects are associated with elevated reactive oxygen species (ROS) production, dysregulation of antioxidant enzymes, and COX-2-mediated inflammation. H2S-induced autophagy/mitophagy is a protective mechanism at intermediate concentrations but fails to mitigate mitochondrial damage at toxic levels. This study underscores the delicate balance between the cytoprotective and cytotoxic effects of exogenous H2S in intestinal cells, helping to develop new therapeutic approaches for gastrointestinal disorders.
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Affiliation(s)
- Domenica Mallardi
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (D.M.); (F.M.); (A.O.); (S.D.); (E.M.)
| | - Guglielmina Chimienti
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy; (G.C.); (C.D.V.)
| | - Fatima Maqoud
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (D.M.); (F.M.); (A.O.); (S.D.); (E.M.)
| | - Antonella Orlando
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (D.M.); (F.M.); (A.O.); (S.D.); (E.M.)
| | - Simona Drago
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (D.M.); (F.M.); (A.O.); (S.D.); (E.M.)
| | - Eleonora Malerba
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (D.M.); (F.M.); (A.O.); (S.D.); (E.M.)
| | - Caterina De Virgilio
- Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy; (G.C.); (C.D.V.)
| | - Hamid I. Akbarali
- Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA;
| | - Francesco Russo
- Functional Gastrointestinal Disorders Research Group, National Institute of Gastroenterology IRCCS “Saverio de Bellis”, Castellana Grotte, 70013 Bari, Italy; (D.M.); (F.M.); (A.O.); (S.D.); (E.M.)
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Cohen Z, Choi J, Peregrina K, Khan S, Wolfson S, Sherman C, Augenlicht L, Kelly L. Diet links gut chemistry with cancer risk in C57Bl/6 mice and human colorectal cancer patients. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.27.635083. [PMID: 39975138 PMCID: PMC11838269 DOI: 10.1101/2025.01.27.635083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/21/2025]
Abstract
Background & Aims Western-style diets, characterized by higher fat and protein, and low micronutrient levels, promote the development of colorectal cancer (CRC). Here, we investigate the role of a Western diet on microbiome composition, sulfide production, and intestinal epithelial damage in pre-CRC mice, and validate taxonomic changes in a meta-analysis of human CRC patients. Methods NWD1 is a purified Western-style diet that produces sporadic intestinal and colon tumors in wild-type C57BL/6 mice in the absence of genetic or carcinogen exposure. To determine how this diet influences cancer risk by shaping microbial composition and sulfide chemistry, mice were fed NWD1 or a purified control diet for 24 weeks. Microbiome composition, sulfide production, and intestinal stem cell mRNA expression were assessed. Observed microbiome changes were validated in a human CRC meta-analysis. Results Fecal sulfide levels were tripled in NWD1-fed mice ( P< 0.00001 ), concurrent with increased abundance of the sulfidogenic Erysipelotrichaceae family. NWD1-fed mice had increased expression of mitochondrial sulfide oxidation genes in Lgr5 hi intestinal stem cells, demonstrating an adaptive response to elevated sulfide. In a meta-analysis of human CRC studies, we observed that Erysipelotrichaceae were associated with CRC, validating both canonical CRC microbes such as Solobacterium moorei and highlighting the potential contribution of previously unrecognized, disease-associated microbes. Conclusions Our analyses connect the risk factors of Western diet, sulfide, and epithelial damage in a pre-cancer mouse model to microbiome changes observed in human CRC patients and suggest that microbial signatures of CRC and gut ecosystem alteration may manifest long before disease development.
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Arellano-Hernández HD, Montes-Carreto LM, Guerrero JA, Martinez-Romero E. The fecal microbiota of the mouse-eared bat (Myotis velifer) with new records of microbial taxa for bats. PLoS One 2024; 19:e0314847. [PMID: 39637086 PMCID: PMC11620696 DOI: 10.1371/journal.pone.0314847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 11/17/2024] [Indexed: 12/07/2024] Open
Abstract
Studies on the fecal microbiome of wild animals reveal valuable information on the feeding habits of the host and the possible roles of bacteria in digestion. In this work we characterized the fecal microbiota of seven male and seven female Myotis velifer bats using the V3-V4 regions of the 16S rRNA gene. Fecal samples were collected at the El Salitre cave in Mexico. We obtained 81 amplicon sequence variants, identifying four phyla, 12 families and 14 genera for females and seven phyla, 21 families and 26 genera for males. The phylum Synergistota is reported for the first time in bats. The most abundant phyla were Pseudomonadota and Fusobacteriota. Male feces showed a greater taxonomic richness than those from females. This study revealed that the fecal microbiota of M. velifer had a unique and more diverse composition compared to the microbiota reported for other bats. We identified 24 families and two abundant genera Cetobacterium and Haematospirillum in both males and females. Cetobacterium may produce vitamin B12 that is not produced by animals and Haematospirillum, which has been reported as an emerging human pathogen, may produce non-volatile organic acids. These genera had not been previously reported in the bat microbiota.
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Affiliation(s)
- Hanya D. Arellano-Hernández
- Labotarorio de Monitoreo y Conservación de Fauna, Facultad de Ciencias Biológicas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México
- Laboratorio de Ecología Genómica, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México
| | - Leslie M. Montes-Carreto
- Laboratorio de Ecología Genómica, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México
| | - José Antonio Guerrero
- Labotarorio de Monitoreo y Conservación de Fauna, Facultad de Ciencias Biológicas, Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, México
| | - Esperanza Martinez-Romero
- Laboratorio de Ecología Genómica, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México
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Datta S, Pasham S, Inavolu S, Boini KM, Koka S. Role of Gut Microbial Metabolites in Cardiovascular Diseases-Current Insights and the Road Ahead. Int J Mol Sci 2024; 25:10208. [PMID: 39337693 PMCID: PMC11432476 DOI: 10.3390/ijms251810208] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/18/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Cardiovascular diseases (CVDs) are the leading cause of premature morbidity and mortality globally. The identification of novel risk factors contributing to CVD onset and progression has enabled an improved understanding of CVD pathophysiology. In addition to the conventional risk factors like high blood pressure, diabetes, obesity and smoking, the role of gut microbiome and intestinal microbe-derived metabolites in maintaining cardiovascular health has gained recent attention in the field of CVD pathophysiology. The human gastrointestinal tract caters to a highly diverse spectrum of microbes recognized as the gut microbiota, which are central to several physiologically significant cascades such as metabolism, nutrient absorption, and energy balance. The manipulation of the gut microbial subtleties potentially contributes to CVD, inflammation, neurodegeneration, obesity, and diabetic onset. The existing paradigm of studies suggests that the disruption of the gut microbial dynamics contributes towards CVD incidence. However, the exact mechanistic understanding of such a correlation from a signaling perspective remains elusive. This review has focused upon an in-depth characterization of gut microbial metabolites and their role in varied pathophysiological conditions, and highlights the potential molecular and signaling mechanisms governing the gut microbial metabolites in CVDs. In addition, it summarizes the existing courses of therapy in modulating the gut microbiome and its metabolites, limitations and scientific gaps in our current understanding, as well as future directions of studies involving the modulation of the gut microbiome and its metabolites, which can be undertaken to develop CVD-associated treatment options. Clarity in the understanding of the molecular interaction(s) and associations governing the gut microbiome and CVD shall potentially enable the development of novel druggable targets to ameliorate CVD in the years to come.
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Affiliation(s)
- Sayantap Datta
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA
| | - Sindhura Pasham
- Department of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
| | - Sriram Inavolu
- Department of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
| | - Krishna M Boini
- Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA
| | - Saisudha Koka
- Department of Pharmaceutical Sciences, Irma Lerma College of Pharmacy, Texas A&M University, Kingsville, TX 78363, USA
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Jin Y, Yuan H, Liu Y, Zhu Y, Wang Y, Liang X, Gao W, Ren Z, Ji X, Wu D. Role of hydrogen sulfide in health and disease. MedComm (Beijing) 2024; 5:e661. [PMID: 39156767 PMCID: PMC11329756 DOI: 10.1002/mco2.661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 08/20/2024] Open
Abstract
In the past, hydrogen sulfide (H2S) was recognized as a toxic and dangerous gas; in recent years, with increased research, we have discovered that H2S can act as an endogenous regulatory transmitter. In mammals, H2S-catalyzing enzymes, such as cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, are differentially expressed in a variety of tissues and affect a variety of biological functions, such as transcriptional and posttranslational modification of genes, activation of signaling pathways in the cell, and metabolic processes in tissues, by producing H2S. Various preclinical studies have shown that H2S affects physiological and pathological processes in the body. However, a detailed systematic summary of these roles in health and disease is lacking. Therefore, this review provides a thorough overview of the physiological roles of H2S in different systems and the diseases associated with disorders of H2S metabolism, such as ischemia-reperfusion injury, hypertension, neurodegenerative diseases, inflammatory bowel disease, and cancer. Meanwhile, this paper also introduces H2S donors and novel release modes, as well as the latest preclinical experimental results, aiming to provide researchers with new ideas to discover new diagnostic targets and therapeutic options.
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Affiliation(s)
- Yu‐Qing Jin
- Henan International Joint Laboratory for Nuclear Protein RegulationSchool of Basic Medical Sciences, School of StomatologyHenan UniversityKaifengHenanChina
| | - Hang Yuan
- Henan International Joint Laboratory for Nuclear Protein RegulationSchool of Basic Medical Sciences, School of StomatologyHenan UniversityKaifengHenanChina
| | - Ya‐Fang Liu
- Henan International Joint Laboratory for Nuclear Protein RegulationSchool of Basic Medical Sciences, School of StomatologyHenan UniversityKaifengHenanChina
| | - Yi‐Wen Zhu
- School of Clinical MedicineHenan UniversityKaifengHenanChina
| | - Yan Wang
- Henan International Joint Laboratory for Nuclear Protein RegulationSchool of Basic Medical Sciences, School of StomatologyHenan UniversityKaifengHenanChina
| | - Xiao‐Yi Liang
- Henan International Joint Laboratory for Nuclear Protein RegulationSchool of Basic Medical Sciences, School of StomatologyHenan UniversityKaifengHenanChina
| | - Wei Gao
- Henan International Joint Laboratory for Nuclear Protein RegulationSchool of Basic Medical Sciences, School of StomatologyHenan UniversityKaifengHenanChina
| | - Zhi‐Guang Ren
- Henan International Joint Laboratory for Nuclear Protein RegulationSchool of Basic Medical Sciences, School of StomatologyHenan UniversityKaifengHenanChina
| | - Xin‐Ying Ji
- Henan International Joint Laboratory for Nuclear Protein RegulationSchool of Basic Medical Sciences, School of StomatologyHenan UniversityKaifengHenanChina
- Faculty of Basic Medical SubjectsShu‐Qing Medical College of ZhengzhouZhengzhouHenanChina
| | - Dong‐Dong Wu
- Henan International Joint Laboratory for Nuclear Protein RegulationSchool of Basic Medical Sciences, School of StomatologyHenan UniversityKaifengHenanChina
- School of StomatologyHenan UniversityKaifengHenanChina
- Department of StomatologyHuaihe Hospital of Henan UniversityKaifengHenanChina
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Flori L, Benedetti G, Martelli A, Calderone V. Microbiota alterations associated with vascular diseases: postbiotics as a next-generation magic bullet for gut-vascular axis. Pharmacol Res 2024; 207:107334. [PMID: 39103131 DOI: 10.1016/j.phrs.2024.107334] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 07/11/2024] [Accepted: 07/29/2024] [Indexed: 08/07/2024]
Abstract
The intestinal microbiota represents a key element in maintaining the homeostasis and health conditions of the host. Vascular pathologies and other risk factors such as aging have been recently associated with dysbiosis. The qualitative and quantitative alteration of the intestinal microbiota hinders correct metabolic homeostasis, causing structural and functional changes of the intestinal wall itself. Impairment of the intestinal microbiota, combined with the reduction of the barrier function, worsen the pathological scenarios of peripheral tissues over time, including the vascular one. Several experimental evidence, collected in this review, describes in detail the changes of the intestinal microbiota in dysbiosis associated with vascular alterations, such as atherosclerosis, hypertension, and endothelial dysfunction, the resulting metabolic disorders and how these can impact on vascular health. In this context, the gut-vascular axis is considered, for the first time, as a merged unit involved in the development and progression of vascular pathologies and as a promising target. Current approaches for the management of dysbiosis such as probiotics, prebiotics and dietary modifications act mainly on the intestinal district. Postbiotics, described as preparation of inanimate microorganisms and/or their components that confers health benefits on the host, represent an innovative strategy for a dual management of intestinal dysbiosis and vascular pathologies. In this context, this review has the further purpose of defining the positive effects of the supplementation of bacterial strains metabolites (short‑chain fatty acids, exopolysaccharides, lipoteichoic acids, gallic acid, and protocatechuic acid) restoring intestinal homeostasis and acting directly on the vascular district through the gut-vascular axis.
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Affiliation(s)
- Lorenzo Flori
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy.
| | - Giada Benedetti
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy.
| | - Alma Martelli
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa 56120, Italy; Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, Pisa 56120, Italy.
| | - Vincenzo Calderone
- Department of Pharmacy, University of Pisa, via Bonanno, Pisa 6-56120, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa 56120, Italy; Interdepartmental Research Centre of Ageing Biology and Pathology, University of Pisa, Pisa 56120, Italy.
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Sun HJ, Lu QB, Zhu XX, Ni ZR, Su JB, Fu X, Chen G, Zheng GL, Nie XW, Bian JS. Pharmacology of Hydrogen Sulfide and Its Donors in Cardiometabolic Diseases. Pharmacol Rev 2024; 76:846-895. [PMID: 38866561 DOI: 10.1124/pharmrev.123.000928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 04/13/2024] [Accepted: 06/10/2024] [Indexed: 06/14/2024] Open
Abstract
Cardiometabolic diseases (CMDs) are major contributors to global mortality, emphasizing the critical need for novel therapeutic interventions. Hydrogen sulfide (H2S) has garnered enormous attention as a significant gasotransmitter with various physiological, pathophysiological, and pharmacological impacts within mammalian cardiometabolic systems. In addition to its roles in attenuating oxidative stress and inflammatory response, burgeoning research emphasizes the significance of H2S in regulating proteins via persulfidation, a well known modification intricately associated with the pathogenesis of CMDs. This review seeks to investigate recent updates on the physiological actions of endogenous H2S and the pharmacological roles of various H2S donors in addressing diverse aspects of CMDs across cellular, animal, and clinical studies. Of note, advanced methodologies, including multiomics, intestinal microflora analysis, organoid, and single-cell sequencing techniques, are gaining traction due to their ability to offer comprehensive insights into biomedical research. These emerging approaches hold promise in characterizing the pharmacological roles of H2S in health and diseases. We will critically assess the current literature to clarify the roles of H2S in diseases while also delineating the opportunities and challenges they present in H2S-based pharmacotherapy for CMDs. SIGNIFICANCE STATEMENT: This comprehensive review covers recent developments in H2S biology and pharmacology in cardiometabolic diseases CMDs. Endogenous H2S and its donors show great promise for the management of CMDs by regulating numerous proteins and signaling pathways. The emergence of new technologies will considerably advance the pharmacological research and clinical translation of H2S.
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Affiliation(s)
- Hai-Jian Sun
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
| | - Qing-Bo Lu
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
| | - Xue-Xue Zhu
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
| | - Zhang-Rong Ni
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
| | - Jia-Bao Su
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
| | - Xiao Fu
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
| | - Guo Chen
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
| | - Guan-Li Zheng
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
| | - Xiao-Wei Nie
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
| | - Jin-Song Bian
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China (H.-J.S., X.-X.Z., Z.-R.N., J.-B.S., X.F., G.C., G.-L.Z.); Department of Endocrinology, Affiliated Hospital of Jiangnan University, Jiangnan University, Wuxi, Jiangsu, China (Q.-B.L.); Shenzhen Key Laboratory of Respiratory Diseases, Shenzhen People's Hospital, Shenzhen, Guangdong, China (X.-W.N.); and Department of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China (J.-S.B.)
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10
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Qi Q, Zhang H, Jin Z, Wang C, Xia M, Chen B, Lv B, Peres Diaz L, Li X, Feng R, Qiu M, Li Y, Meseguer D, Zheng X, Wang W, Song W, Huang H, Wu H, Chen L, Schneeberger M, Yu X. Hydrogen sulfide produced by the gut microbiota impairs host metabolism via reducing GLP-1 levels in male mice. Nat Metab 2024; 6:1601-1615. [PMID: 39030389 DOI: 10.1038/s42255-024-01068-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 05/21/2024] [Indexed: 07/21/2024]
Abstract
Dysbiosis of the gut microbiota has been implicated in the pathogenesis of metabolic syndrome (MetS) and may impair host metabolism through harmful metabolites. Here, we show that Desulfovibrio, an intestinal symbiont enriched in patients with MetS, suppresses the production of the gut hormone glucagon-like peptide 1 (GLP-1) through the production of hydrogen sulfide (H2S) in male mice. Desulfovibrio-derived H2S is found to inhibit mitochondrial respiration and induce the unfolded protein response in intestinal L cells, thereby hindering GLP-1 secretion and gene expression. Remarkably, blocking Desulfovibrio and H2S with an over-the-counter drug, bismuth subsalicylate, improves GLP-1 production and ameliorates diet-induced metabolic disorder in male mice. Together, our study uncovers that Desulfovibrio-derived H2S compromises GLP-1 production, shedding light on the gut-relayed mechanisms by which harmful microbiota-derived metabolites impair host metabolism in MetS and suggesting new possibilities for treating MetS.
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Affiliation(s)
- Qingqing Qi
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
| | - Huijie Zhang
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
| | - Zheyu Jin
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
| | - Changchun Wang
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
| | - Mengyu Xia
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
| | - Bandy Chen
- Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA
| | - Bomin Lv
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
- Human Phenome Institute, Fudan University, Shanghai, China
| | - Ludmila Peres Diaz
- Department of Immunobiology, Institute for Biomolecular Design and Discovery, Yale University School of Medicine, New Haven, CT, USA
| | - Xue Li
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
| | - Ru Feng
- Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mengdi Qiu
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
| | - Yang Li
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - David Meseguer
- Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA
| | - Xiaojiao Zheng
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Wang
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
| | - Wei Song
- Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China
| | - He Huang
- Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China
| | - Hao Wu
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China
- Human Phenome Institute, Fudan University, Shanghai, China
| | - Lei Chen
- Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Marc Schneeberger
- Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
| | - Xiaofei Yu
- State Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan University, Shanghai, China.
- Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, China.
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11
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Pimenta AI, Bernardino RM, Pereira IAC. Role of sulfidogenic members of the gut microbiota in human disease. Adv Microb Physiol 2024; 85:145-200. [PMID: 39059820 DOI: 10.1016/bs.ampbs.2024.04.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
The human gut flora comprises a dynamic network of bacterial species that coexist in a finely tuned equilibrium. The interaction with intestinal bacteria profoundly influences the host's development, metabolism, immunity, and overall health. Furthermore, dysbiosis, a disruption of the gut microbiota, can induce a variety of diseases, not exclusively associated with the intestinal tract. The increased consumption of animal protein, high-fat and high-sugar diets in Western countries has been implicated in the rise of chronic and inflammatory illnesses associated with dysbiosis. In particular, this diet leads to the overgrowth of sulfide-producing bacteria, known as sulfidogenic bacteria, which has been linked to inflammatory bowel diseases and colorectal cancer, among other disorders. Sulfidogenic bacteria include sulfate-reducing bacteria (Desulfovibrio spp.) and Bilophila wadsworthia among others, which convert organic and inorganic sulfur compounds to sulfide through the dissimilatory sulfite reduction pathway. At high concentrations, sulfide is cytotoxic and disrupts the integrity of the intestinal epithelium and mucus barrier, triggering inflammation. Besides producing sulfide, B. wadsworthia has revealed significant pathogenic potential, demonstrated in the ability to cause infection, adhere to intestinal cells, promote inflammation, and compromise the integrity of the colonic mucus layer. This review delves into the mechanisms by which taurine and sulfide-driven gut dysbiosis contribute to the pathogenesis of sulfidogenic bacteria, and discusses the role of these gut microbes, particularly B. wadsworthia, in human diseases.
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Affiliation(s)
- Andreia I Pimenta
- Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal
| | - Raquel M Bernardino
- Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal
| | - Inês A C Pereira
- Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
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12
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Xu R, Feng N, Li Q, Wang H, Li L, Feng X, Su Y, Zhu W. Pectin supplementation accelerates post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential. THE ISME JOURNAL 2024; 18:wrae101. [PMID: 38857378 PMCID: PMC11203915 DOI: 10.1093/ismejo/wrae101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 05/31/2024] [Accepted: 06/09/2024] [Indexed: 06/12/2024]
Abstract
Antibiotic-induced gut dysbiosis (AID) presents a big challenge to host health, and the recovery from this dysbiosis is often slow and incomplete. AID is typically characterized by elevation in redox potential, Enterobacteriaceae load, and aerobic metabolism. In our previous study, a pectin-enriched diet was demonstrated to decrease fecal redox potential and modulate the gut microbiome. Therefore, we propose that pectin supplementation may modulate gut redox potential and favor post-antibiotic gut microbiome reconstitution from dysbiosis. In the present study, rats with AIDwere used to investigate the effects of pectin supplementation on post-antibiotic gut microbiome reconstitution from dysbiosis. The results showed that pectin supplementation accelerated post-antibiotic reconstitution of gut microbiome composition and function and led to enhancement of anabolic reductive metabolism and weakening of catabolic oxidative pathways. These results were corroborated by the measurement of redox potential, findings suggesting that pectin favors post-antibiotic recovery from dysbiosis. Pectin-modulated fecal microbiota transplantation accelerated the decrease in antibiotics-elevated redox potential and Enterobacteriaceae load similarly to pectin supplementation. Moreover, both pectin supplementation and Pectin-modulated fecal microbiota transplantation enriched anaerobic members, primarily from Lachnospiraceae orchestration with enhancement of microbial reductive metabolism in post-antibiotic rats. These findings suggested that pectin supplementation accelerated post-antibiotic gut microbiome reconstitution orchestrated with reduced gut redox potential and that the effect of pectin on redox potential was mediated by remodeling of the intestinal microbiota.
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Affiliation(s)
- Rongying Xu
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Ni Feng
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Qiuke Li
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Hongyu Wang
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Lian Li
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Xiaobo Feng
- Research Institute of General Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210095, China
| | - Yong Su
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
| | - Weiyun Zhu
- Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China
- National Center for International Research on Animal Gut Nutrition, Nanjing Agricultural University, Nanjing 210095, China
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13
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Luo S, Kong C, Ye D, Liu X, Wang Y, Meng G, Han Y, Xie L, Ji Y. Protein Persulfidation: Recent Progress and Future Directions. Antioxid Redox Signal 2023; 39:829-852. [PMID: 36943282 DOI: 10.1089/ars.2022.0064] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/23/2023]
Abstract
Significance: Hydrogen sulfide (H2S) is considered to be a gasotransmitter along with carbon monoxide (CO) and nitric oxide (NO), and is known as a key regulator of physiological and pathological activities. S-sulfhydration (also known as persulfidation), a mechanism involving the formation of protein persulfides by modification of cysteine residues, is proposed here to explain the multiple biological functions of H2S. Investigating the properties of protein persulfides can provide a foundation for further understanding of the potential functions of H2S. Recent Advances: Multiple methods have been developed to determine the level of protein persulfides. It has been demonstrated that protein persulfidation is involved in many biological processes through various mechanisms including the regulation of ion channels, enzymes, and transcription factors, as well as influencing protein-protein interactions. Critical Issues: Some technical and theoretical questions remain to be solved. These include how to improve the specificity of the detection methods for protein persulfidation, why persulfidation typically occurs on one or a few thiols within a protein, how this modification alters protein functions, and whether protein persulfidation has organ-specific patterns. Future Directions: Optimizing the detection methods and elucidating the properties and molecular functions of protein persulfidation would be beneficial for current therapeutics. In this review, we introduce the detailed mechanism of the persulfidation process and discuss persulfidation detection methods. In addition, this review summarizes recent discoveries of the selectivity of protein persulfidation and the regulation of protein functions and cell signaling pathways by persulfidation. Antioxid. Redox Signal. 39, 829-852.
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Affiliation(s)
- Shanshan Luo
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, China
| | - Chuiyu Kong
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, China
| | - Danyu Ye
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, China
| | - Xingeng Liu
- Key Laboratory of Targeted Intervention of Cardiovascular Disease, Nanjing Medical University, Nanjing, China
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China
| | - Yu Wang
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, China
| | - Guoliang Meng
- Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China
| | - Yi Han
- Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Liping Xie
- Key Laboratory of Targeted Intervention of Cardiovascular Disease, Nanjing Medical University, Nanjing, China
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China
- The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
| | - Yong Ji
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Nanjing, China
- Key Laboratory of Targeted Intervention of Cardiovascular Disease, Nanjing Medical University, Nanjing, China
- Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China
- The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Nanjing, China
- National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin, China
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14
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Luo S, Ji Y. Response by Luo and Ji to Letter Regarding Article, "Endothelial HDAC1-ZEB2-NuRD Complex Drives Aortic Aneurysm and Dissection Through Regulation of Protein S-Sulfhydration". Circulation 2023; 148:1415-1416. [PMID: 37903184 DOI: 10.1161/circulationaha.123.066273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/01/2023]
Affiliation(s)
- Shanshan Luo
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, and Gusu School, Nanjing Medical University, Nanjing, China (S.L., Y.J.)
| | - Yong Ji
- Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, and Gusu School, Nanjing Medical University, Nanjing, China (S.L., Y.J.)
- State Key Laboratory of Frigid Zone Cardiovascular Diseases, Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy, Key Laboratory of Cardiovascular Medicine Research, and Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, NHC Key Laboratory of Cell Transplantation, the Central Laboratory of the First Affiliated Hospital, Harbin Medical University, Heilongjiang, China (Y.J.)
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15
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Marcelino VR, Welsh C, Diener C, Gulliver EL, Rutten EL, Young RB, Giles EM, Gibbons SM, Greening C, Forster SC. Disease-specific loss of microbial cross-feeding interactions in the human gut. Nat Commun 2023; 14:6546. [PMID: 37863966 PMCID: PMC10589287 DOI: 10.1038/s41467-023-42112-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Accepted: 09/27/2023] [Indexed: 10/22/2023] Open
Abstract
Many gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized. Here, we introduce a Metabolite Exchange Score (MES) to quantify those interactions. Using metabolic models of prokaryotic metagenome-assembled genomes from over 1600 individuals, MES allows us to identify and rank metabolic interactions that are significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases. When applied to a Crohn's disease case-control study, our approach identifies a lack of species with the ability to consume hydrogen sulfide as the main distinguishing microbiome feature of disease. We propose that our conceptual framework will help prioritize in-depth analyses, experiments and clinical targets, and that targeting the restoration of microbial cross-feeding interactions is a promising mechanism-informed strategy to reconstruct a healthy gut ecosystem.
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Affiliation(s)
- Vanessa R Marcelino
- Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, 3168, Australia.
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
- Melbourne Integrative Genomics, School of BioSciences, University of Melbourne, Parkville, VIC, 3010, Australia.
- Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, VIC, 3010, Australia.
| | - Caitlin Welsh
- Department of Microbiology, Biomedicine Discovery Institute, Clayton, VIC, 3800, Australia
| | | | - Emily L Gulliver
- Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, 3168, Australia
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia
| | - Emily L Rutten
- Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, 3168, Australia
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia
| | - Remy B Young
- Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, 3168, Australia
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia
| | - Edward M Giles
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia
- Department of Paediatrics, Monash University, Clayton, VIC, 3168, Australia
| | - Sean M Gibbons
- Institute for Systems Biology, Seattle, WA, 98109, USA
- Department of Bioengineering, University of Washington, Seattle, WA, 98195, USA
- Department of Genome Sciences, University of Washington, Seattle, WA, 98195, USA
- eScience Institute, University of Washington, Seattle, WA, 98195, USA
| | - Chris Greening
- Department of Microbiology, Biomedicine Discovery Institute, Clayton, VIC, 3800, Australia
| | - Samuel C Forster
- Department of Molecular and Translational Sciences, Monash University, Clayton, VIC, 3168, Australia.
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, 3168, Australia.
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16
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Camilleri M, BouSaba J. Potential Value of Biomarker-Based Approaches for Evaluation and Management of Costly Functional Gastrointestinal Diseases. Clin Gastroenterol Hepatol 2023; 21:2462-2472. [PMID: 37164114 PMCID: PMC10524924 DOI: 10.1016/j.cgh.2023.04.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/18/2023] [Accepted: 04/24/2023] [Indexed: 05/12/2023]
Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota.
| | - Joelle BouSaba
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic, Rochester, Minnesota
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17
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Stummer N, Feichtinger RG, Weghuber D, Kofler B, Schneider AM. Role of Hydrogen Sulfide in Inflammatory Bowel Disease. Antioxidants (Basel) 2023; 12:1570. [PMID: 37627565 PMCID: PMC10452036 DOI: 10.3390/antiox12081570] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 07/28/2023] [Accepted: 08/04/2023] [Indexed: 08/27/2023] Open
Abstract
Hydrogen sulfide (H2S), originally known as toxic gas, has now attracted attention as one of the gasotransmitters involved in many reactions in the human body. H2S has been assumed to play a role in the pathogenesis of many chronic diseases, of which the exact pathogenesis remains unknown. One of them is inflammatory bowel disease (IBD), a chronic intestinal disease subclassified as Crohn's disease (CD) and ulcerative colitis (UC). Any change in the amount of H2S seems to be linked to inflammation in this illness. These changes can be brought about by alterations in the microbiota, in the endogenous metabolism of H2S and in the diet. As both too little and too much H2S drive inflammation, a balanced level is needed for intestinal health. The aim of this review is to summarize the available literature published until June 2023 in order to provide an overview of the current knowledge of the connection between H2S and IBD.
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Affiliation(s)
- Nathalie Stummer
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
| | - René G. Feichtinger
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
| | - Daniel Weghuber
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
| | - Barbara Kofler
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
- Research Program for Receptor Biochemistry and Tumor Metabolism, Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Anna M. Schneider
- Department of Pediatrics, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria; (N.S.); (R.G.F.); (D.W.); (B.K.)
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18
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Ashkar F, Wu J. Effects of Food Factors and Processing on Protein Digestibility and Gut Microbiota. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023. [PMID: 37267055 DOI: 10.1021/acs.jafc.3c00442] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
Abstract
Protein is an essential macronutrient. The nutritional needs of dietary proteins are met by digestion and absorption in the small intestine. Indigestible proteins are further metabolized in the gut and produce metabolites via protein fermentation. Thus, protein indigestibility exerts a wide range of effects on gut microbiota composition and function. This review aims to discuss protein digestibility, the effects of food factors, such as protein sources, intake level, and amino acid composition, and making meat analogues. Besides, it provides an inventory of antinutritional factors and processing techniques that influence protein digestibility and, consequently, the diversity and composition of intestinal microbiota. Future studies are warranted to understand the implication of plant-based analogues on protein digestibility and gut microbiota and to elucidate the mechanisms concerning protein digestibility to host gut microbiota using various omics techniques.
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Affiliation(s)
- Fatemeh Ashkar
- Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2R3, Canada
| | - Jianping Wu
- Department of Agricultural Food and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2R3, Canada
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19
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Lajin B, Obermayer-Pietsch B, Somma R, Goessler W. A time-course investigation of the human urinary excretion of the hydrogen sulfide biomarker trimethylsulfonium. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2023; 100:104162. [PMID: 37245608 DOI: 10.1016/j.etap.2023.104162] [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: 02/19/2023] [Revised: 05/22/2023] [Accepted: 05/25/2023] [Indexed: 05/30/2023]
Abstract
Hydrogen sulfide is a toxic gas but also recognized as an endogenously produced metabolite in humans playing key roles. We previously identified trimethylsulfonium, which can be a methylation product of hydrogen sulfide but the stability in the production of trimethylsulfonium has not been investigated. In the present work, the intra- and inter-individual variability in the excretion of trimethylsulfonium over 2 months in a group of healthy volunteers was investigated. Urinary levels of trimethylsulfonium (mean: 56 nM, 95% CI: 48-68 nM) were > 100-fold lower than the conventional hydrogen sulfide biomarker thiosulfate (13 µM, 12-15 µM) and the precursor for endogenous hydrogen sulfide production cystine (47 µM, 44-50 µM). There was no correlation between urinary trimethylsulfonium and thiosulfate. Higher intra-individual variability in the excretion of trimethylsulfonium (generally 2-8 fold) than that for cystine (generally 2-3 fold) was found. Trimethylsulfonium displayed significant inter-individual variability with two concentration clusters at 117 nM (97-141) and 27 nM (22-34). In conclusion, the observed inter- and intra-individual variability must be considered when using urinary trimethylsulfonium as a biomarker.
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Affiliation(s)
- Bassam Lajin
- Institute of Chemistry, Analytical Chemistry for the Health and Environment, University of Graz, Universitaetsplatz 1, 8010 Graz, Austria; Institute of Chemistry, ChromICP, University of Graz, Universitaetsplatz 1, 8010 Graz, Austria.
| | - Barbara Obermayer-Pietsch
- Division of Endocrinology and Diabetology, Endocrinology Lab Platform, Department of Internal Medicine and Gynecology and Obstetrics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria
| | - Renato Somma
- Istituto Nazionale di Geofisica e Vulcanologia Sezione di Napoli Osservatorio Vesuviano, 80124 Napoli, Italy; Consiglio Nazionale delle Ricerche ISMAR Istituto di Scienze Marine Napoli Calata Porta Di Massa, Porto Di Napoli 80, 80133 Napoli, Italy; Consiglio Nazionale delle Ricerche IRISS Istituto di Ricerca su Innovazione e Servizi per lo Sviluppo, Via Guglielmo Sanfelice, 8, 80134 Napoli, Italy
| | - Walter Goessler
- Institute of Chemistry, Analytical Chemistry for the Health and Environment, University of Graz, Universitaetsplatz 1, 8010 Graz, Austria
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20
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Chen CJ, Cheng MC, Hsu CN, Tain YL. Sulfur-Containing Amino Acids, Hydrogen Sulfide, and Sulfur Compounds on Kidney Health and Disease. Metabolites 2023; 13:688. [PMID: 37367846 DOI: 10.3390/metabo13060688] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/23/2023] [Accepted: 05/24/2023] [Indexed: 06/28/2023] Open
Abstract
Hydrogen sulfide (H2S) plays a decisive role in kidney health and disease. H2S can ben synthesized via enzymatic and non-enzymatic pathways, as well as gut microbial origins. Kidney disease can originate in early life induced by various maternal insults throughout the process, namely renal programming. Sulfur-containing amino acids and sulfate are essential in normal pregnancy and fetal development. Dysregulated H2S signaling behind renal programming is linked to deficient nitric oxide, oxidative stress, the aberrant renin-angiotensin-aldosterone system, and gut microbiota dysbiosis. In animal models of renal programming, treatment with sulfur-containing amino acids, N-acetylcysteine, H2S donors, and organosulfur compounds during gestation and lactation could improve offspring's renal outcomes. In this review, we summarize current knowledge regarding sulfide/sulfate implicated in pregnancy and kidney development, current evidence supporting the interactions between H2S signaling and underlying mechanisms of renal programming, and recent advances in the beneficial actions of sulfide-related interventions on the prevention of kidney disease. Modifying H2S signaling is the novel therapeutic and preventive approach to reduce the global burden of kidney disease; however, more work is required to translate this into clinical practice.
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Affiliation(s)
- Chih-Jen Chen
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Ming-Chou Cheng
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - You-Lin Tain
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
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21
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Blachier F. Amino Acid-Derived Bacterial Metabolites in the Colorectal Luminal Fluid: Effects on Microbial Communication, Metabolism, Physiology, and Growth. Microorganisms 2023; 11:1317. [PMID: 37317289 DOI: 10.3390/microorganisms11051317] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 05/14/2023] [Accepted: 05/15/2023] [Indexed: 06/16/2023] Open
Abstract
Undigested dietary and endogenous proteins, as well as unabsorbed amino acids, can move from the terminal part of the ileum into the large intestine, where they meet a dense microbial population. Exfoliated cells and mucus released from the large intestine epithelium also supply nitrogenous material to this microbial population. The bacteria in the large intestine luminal fluid release amino acids from the available proteins, and amino acids are then used for bacterial protein synthesis, energy production, and in other various catabolic pathways. The resulting metabolic intermediaries and end products can then accumulate in the colorectal fluid, and their concentrations appear to depend on different parameters, including microbiota composition and metabolic activity, substrate availability, and the capacity of absorptive colonocytes to absorb these metabolites. The aim of the present review is to present how amino acid-derived bacterial metabolites can affect microbial communication between both commensal and pathogenic microorganisms, as well as their metabolism, physiology, and growth.
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Affiliation(s)
- François Blachier
- Université Paris-Saclay, AgroParisTech, INRAe, UMR PNCA, 91120 Palaiseau, France
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22
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Larraufie P, Haroun K, Fleury C, Andriamihaja M, Blachier F. Regulation of enteroendocrine cell respiration by the microbial metabolite hydrogen sulfide. Front Endocrinol (Lausanne) 2023; 14:1123364. [PMID: 37229450 PMCID: PMC10203461 DOI: 10.3389/fendo.2023.1123364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 04/12/2023] [Indexed: 05/27/2023] Open
Abstract
Endocrine functions of the gut are supported by a scattered population of cells, the enteroendocrine cells (EECs). EECs sense their environment to secrete hormones in a regulated manner. Distal EECs are in contact with various microbial compounds including hydrogen sulfide (H2S) which modulate cell respiration with potential consequences on EEC physiology. However, the effect of H2S on gut hormone secretion remains discussed and the importance of the modulation of cell metabolism on EEC functions remains to be deciphered. The aim of this project was to characterize the metabolic response of EECs to H2S and the consequences on GLP-1 secretion. We used cell line models of EECs to assess their capacity to metabolize H2S at low concentration and the associated modulation of cell respiration. We confirmed that like what is observed in colonocytes, colonic EEC model, NCI-h716 cell line rapidly metabolizes H2S at low concentrations, resulting in transient increased respiration. Higher concentrations of H2S inhibited this respiration, with the concentration threshold for inhibition depending on cell density. However, increased or inhibited oxidative respiration had little effect on acute GLP-1 secretion. Overall, we present here a first study showing the EEC capacity to detoxify low concentrations of H2S and used this model to acutely address the importance of cell respiration on secretory activity.
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Affiliation(s)
- Pierre Larraufie
- Université Paris-Saclay, AgroParisTech, INRAE, UMR PNCA, Palaiseau, France
- Université Paris-Saclay, INRAE, AgroParisTech, Micalis Institute, Jouy-en-Josas, France
| | - Kenza Haroun
- Université Paris-Saclay, AgroParisTech, INRAE, UMR PNCA, Palaiseau, France
| | - Carla Fleury
- Université Paris-Saclay, AgroParisTech, INRAE, UMR PNCA, Palaiseau, France
| | | | - François Blachier
- Université Paris-Saclay, AgroParisTech, INRAE, UMR PNCA, Palaiseau, France
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23
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Colon-targeted bacterial hydrogel for tumor vascular normalization and improved chemotherapy. J Control Release 2023; 356:59-71. [PMID: 36842488 DOI: 10.1016/j.jconrel.2023.02.028] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 01/13/2023] [Accepted: 02/19/2023] [Indexed: 02/28/2023]
Abstract
The endogenous H2S plays an important role in the occurrence and development of colon cancer, and is related to the abnormal blood vessels. Here, we reported on a sulfhydryl hyaluronid-based hydrogel (HA-SH) synthesized by amide reaction and further obtained a bacterial hydrogel by loading Thiobacillus denitrificans to the hydrogel for targeting adhesion to the colon. It was found that the loaded bacteria in HA-SH hydrogel can scavenge excess H2S in colon cancer, then promote tumor vascular normalization and improve the delivery of chemotherapy drug CPT to inhibit tumor progression. Both in vivo and in vitro experiments show that the self-crosslinked bacterial hydrogel has satisfactory effects in inhibiting tumor progression and promoting tumor vascular normalization in colon cancer. This study presents an efficient method to target the colon and consume overexpressed H2S in colon cancer to inhabit tumor progression, providing a new way for oral drug treatment of colon cancer.
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24
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Lin H, Yu Y, Zhu L, Lai N, Zhang L, Guo Y, Lin X, Yang D, Ren N, Zhu Z, Dong Q. Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies. Redox Biol 2023; 59:102601. [PMID: 36630819 PMCID: PMC9841368 DOI: 10.1016/j.redox.2023.102601] [Citation(s) in RCA: 49] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 01/01/2023] [Accepted: 01/02/2023] [Indexed: 01/09/2023] Open
Abstract
Hydrogen sulfide (H2S) is an important signaling molecule in colorectal cancer (CRC). It is produced in the colon by the catalytic synthesis of the colonocytes' enzymatic systems and the release of intestinal microbes, and is oxidatively metabolized in the colonocytes' mitochondria. Both endogenous H2S in colonic epithelial cells and exogenous H2S in intestinal lumen contribute to the onset and progression of CRC. The up-regulation of endogenous synthetases is thought to be the cause of the elevated H2S levels in CRC cells. Different diagnostic probes and combination therapies, as well as tumor treatment approaches through H2S modulation, have been developed in recent years and have become active area of investigation for the diagnosis and treatment of CRC. In this review, we focus on the specific mechanisms of H2S production and oxidative metabolism as well as the function of H2S in the occurrence, progression, diagnosis, and treatment of CRC. We also discuss the present challenges and provide insights into the future research of this burgeoning field.
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Affiliation(s)
- Hanchao Lin
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China; Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, China
| | - Yixin Yu
- College of Materials Science and Engineering, Qingdao University of Science and Technology, China
| | - Le Zhu
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, China
| | - Nannan Lai
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China
| | - Luming Zhang
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China
| | - Yu Guo
- Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, China
| | - Xinxin Lin
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China
| | - Dongqin Yang
- Department of Digestive Diseases, Huashan Hospital, Fudan University, China.
| | - Ning Ren
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China; Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, And Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, China.
| | - Zhiling Zhu
- College of Materials Science and Engineering, Qingdao University of Science and Technology, China.
| | - Qiongzhu Dong
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission, Minhang Hospital, Fudan University, China.
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25
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Dong Y, Wang J, Gao Z, Di J, Wang D, Guo X, Hu Z, Gao X, Wang Y. Study on Growth Influencing Factors and Desulfurization Performance of Sulfate Reducing Bacteria Based on the Response Surface Methodology. ACS OMEGA 2023; 8:4046-4059. [PMID: 36743035 PMCID: PMC9893483 DOI: 10.1021/acsomega.2c06931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 01/04/2023] [Indexed: 06/18/2023]
Abstract
Sulfate reducing bacteria (SRB) can simultaneously and efficiently remove SO4 2- and heavy metal ions from acid mine drainage (AMD). Environmental factors have a great influence on AMD treated by SRB metabolic reducing sulfate. Providing a suitable growth environment can improve the effect of SRB on AMD. In this paper, the wet soil around the tailings reservoir was used as seed mud to enrich SRB. Based on the single factor experiment method and the response surface methodology (RSM), the effects of temperature, environmental pH value, S2- concentration, and COD/SO4 2- on the growth of SRB were analyzed. The effects of environmental factors such as temperature and pH on the desulfurization performance of SRB were investigated. The results showed that the growth curve of SRB was "S" type. SRB was in the logarithmic phase when cultured for 14-86 h, with high activity and vigorous growth metabolism. When the temperature is 32∼35 °C, the activity of SRB is the highest. With the gradual increase of the S2- concentration in the culture system, SRB activity will be inhibited and even lead to SRB cell death. The environmental pH value that SRB can tolerate is 5∼8, and when the environmental pH value is 7∼8, the SRB activity is the strongest. The chemical oxygen demand (COD)/SO4 2- that is most suitable for SRB growth is 2. The optimal growth conditions of SRB obtained from RSM were as follows: culture temperature at 34.74 °C, initial pH being 8.00, and initial COD/SO4 2- being 1.98. Under these conditions, the OD600 value was 1.45, the pH value was 9.37, the oxidation reduction potential (ORP) value was -399 mV, and the removal percentage of SO4 2- was 88.74%. The results of RSM showed that the effects of culture temperature, environmental pH, and COD/SO4 2- on the desulfurization performance of SRB were extremely significant. The order of affecting the removal of SO4 2- by SRB was environmental pH > temperature > COD/SO4 2-.
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Affiliation(s)
- Yanrong Dong
- College
of Civil Engineering, Liaoning Technical
University, Fuxin123000, China
- College
of Mining, Liaoning Technical University, Fuxin123000, China
| | - Jingbo Wang
- College
of Civil Engineering, Liaoning Technical
University, Fuxin123000, China
| | - Ziqing Gao
- College
of Civil Engineering, Liaoning Technical
University, Fuxin123000, China
| | - Junzhen Di
- College
of Civil Engineering, Liaoning Technical
University, Fuxin123000, China
| | - Dong Wang
- College
of Mining, Liaoning Technical University, Fuxin123000, China
| | - Xuying Guo
- College
of Science, Liaoning Technical University, Fuxin123000, China
| | - Zhiyong Hu
- College
of Mining, Liaoning Technical University, Fuxin123000, China
| | - Xinle Gao
- College
of Mining, Liaoning Technical University, Fuxin123000, China
| | - Yunfeng Wang
- College
of Civil Engineering, Liaoning Technical
University, Fuxin123000, China
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26
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Cysteine Biosynthesis in Campylobacter jejuni: Substrate Specificity of CysM and the Dualism of Sulfide. Biomolecules 2022; 13:biom13010086. [PMID: 36671471 PMCID: PMC9855970 DOI: 10.3390/biom13010086] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 12/28/2022] [Accepted: 12/30/2022] [Indexed: 01/04/2023] Open
Abstract
Campylobacter jejuni is a highly successful enteric pathogen with a small, host-adapted genome (1.64 Mbp, ~1650 coding genes). As a result, C. jejuni has limited capacity in numerous metabolic pathways, including sulfur metabolism. Unable to utilise ionic sulfur, C. jejuni relies on the uptake of exogenous cysteine and its derivatives for its supply of this essential amino acid. Cysteine can also be synthesized de novo by the sole cysteine synthase, CysM. In this study, we explored the substrate specificity of purified C. jejuni CysM and define it as an O-acetyl-L-serine sulfhydrylase with an almost absolute preference for sulfide as sulfur donor. Sulfide is produced in abundance in the intestinal niche C. jejuni colonises, yet sulfide is generally viewed as highly toxic to bacteria. We conducted a series of growth experiments in sulfur-limited media and demonstrate that sulfide is an excellent sulfur source for C. jejuni at physiologically relevant concentrations, combating the view of sulfide as a purely deleterious compound to bacteria. Nonetheless, C. jejuni is indeed inhibited by elevated concentrations of sulfide and we sought to understand the targets involved. Surprisingly, we found that inactivation of the sulfide-sensitive primary terminal oxidase, the cbb3-type cytochrome c oxidase CcoNOPQ, did not explain the majority of growth inhibition by sulfide. Therefore, further work is required to reveal the cellular targets responsible for sulfide toxicity in C. jejuni.
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27
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Mishra K, Isali I, Sindhani M, Prunty M, Bell S, Mahran A, Damiani G, Ghannoum M, Retuerto M, Kutikov A, Ross J, Woo LL, Abbosh PH, Bukavina L. Characterization of Changes in Penile Microbiome Following Pediatric Circumcision. Eur Urol Focus 2022:S2405-4569(22)00290-5. [PMID: 36566099 DOI: 10.1016/j.euf.2022.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/25/2022] [Accepted: 12/08/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome. OBJECTIVE Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and energy metabolism. DESIGN, SETTING, AND PARTICIPANTS We analyzed 11 paired samples, periurethral collection, before and after circumcision, to generate microbiome and mycobiome profiling. Sample preparation of 16S ribosomal RNA and internal transcribed spacer sequencing was adapted from the methods developed by the National Institutes of Health Human Microbiome Project. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We obtained the predictive functional attributes of the microbial communities between samples using Silva-Tax4Fun and the Greengenes-Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) approach. The predictive functioning of the microbial communities was determined by linearly combining the normalized taxonomic abundances into the precomputed association matrix of Kyoto Encyclopedia of Genes and Genomes orthology reference profiles. RESULTS AND LIMITATIONS Several notable microbiome and mycobiome compositional differences were observed between pre- and postcircumcision patients. Pairwise comparisons across taxa revealed a significant decrease (p < 0.05, false discovery rate corrected) of microbiome organisms (Clostridiales, Bacteroidales, and Campylobacterales) and mycobiome (Saccharomycetales and Pleosporales) following circumcision. A total of 14 pathways were found to differ in abundance between the pre- and postcircumcision groups (p < 0.005, false discovery rate <0.1 and linear discriminant analysis score >3; five enriched and nine depleted). The pathways reduced after circumcision were mostly involved with amino acid and glucose metabolism, while pathways prior to circumcision were enriched in genetic information processing and transcription processes. As expected, enrichment in methyl-accepting chemotaxis protein, an integral membrane protein involved in directed motility of microbes to chemical cues and environment, occurred prior to circumcision, while the filamentous hemagglutinin pathway (a strong immunogenic protein) was depleted after circumcision CONCLUSIONS: Our results offer greater insight into the host-microbiota relationship of penile circumcision and may serve to lay the groundwork for future studies focused on drivers of inflammation, infection, and oncogenesis. PATIENT SUMMARY Our study showed a significant reduction in bacteria and fungi after circumcision, particularly anaerobic bacteria, which are known to be potential inducers of inflammation and cancer. This is the first study of its kind showing the changes in microbiome after circumcision, and some of the changes that occur in healthy infants after circumcision that may explain the differences in cancer and inflammatory disorders in adulthood.
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Affiliation(s)
- Kirtishri Mishra
- Department of Urology, New York University, Langone Medical Center, New York, NY, USA; Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA
| | - Ilaha Isali
- Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA
| | | | - Megan Prunty
- Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA
| | | | - Amr Mahran
- Department of Urology, University of Tennessee, Knoxville, TN, USA; Department of Urology, Assiut University, Assiut, Egypt
| | - Giovanni Damiani
- Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy
| | - Mahmoud Ghannoum
- Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Case Western Reserve School of Medicine, Center for Medical Mycology, Cleveland, OH, USA
| | - Mauricio Retuerto
- Case Western Reserve School of Medicine, Center for Medical Mycology, Cleveland, OH, USA
| | | | - Jonathan Ross
- Department of Urology, Rush University, Chicago, IL, USA
| | - Lynn L Woo
- Einstein Medical Center, Department of Urology, Philadelphia, PA, USA
| | - Philip H Abbosh
- Fox Chase Cancer Center, Philadelphia, PA, USA; Department of Urology, Rainbow Babies and Children's Hospital, Cleveland, OH, USA
| | - Laura Bukavina
- Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA; Fox Chase Cancer Center, Philadelphia, PA, USA.
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28
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Stummer N, Weghuber D, Feichtinger RG, Huber S, Mayr JA, Kofler B, Neureiter D, Klieser E, Hochmann S, Lauth W, Schneider AM. Hydrogen Sulfide Metabolizing Enzymes in the Intestinal Mucosa in Pediatric and Adult Inflammatory Bowel Disease. Antioxidants (Basel) 2022; 11:2235. [PMID: 36421421 PMCID: PMC9686699 DOI: 10.3390/antiox11112235] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/02/2022] [Accepted: 11/08/2022] [Indexed: 08/27/2023] Open
Abstract
Hydrogen sulfide (H2S) is a toxic gas that has important regulatory functions. In the colon, H2S can be produced and detoxified endogenously. Both too little and too much H2S exposure are associated with inflammatory bowel disease (IBD), a chronic intestinal disease mainly classified as Crohn's disease (CD) and ulcerative colitis (UC). As the pathogenesis of IBD remains elusive, this study's aim was to investigate potential differences in the expression of H2S-metabolizing enzymes in normal aging and IBD. Intestinal mucosal biopsies of 25 adults and 22 children with IBD along with those of 26 healthy controls were stained immunohistochemically for cystathionine-γ-lyase (CSE), 3-mercapto-sulfurtransferase (3-MST), ethylmalonic encephalopathy 1 protein (ETHE1), sulfide:quinone oxidoreductase (SQOR) and thiosulfate sulfurtransferase (TST). Expression levels were calculated by multiplication of the staining intensity and percentage of positively stained cells. Healthy adults showed an overall trend towards lower expression of H2S-metabolizing enzymes than healthy children. Adults with IBD also tended to have lower expression compared to controls. A similar trend was seen in the enzyme expression of children with IBD compared to controls. These results indicate an age-related decrease in the expression of H2S-metabolizing enzymes and a dysfunctional H2S metabolism in IBD, which was less pronounced in children.
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Affiliation(s)
- Nathalie Stummer
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Daniel Weghuber
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - René G. Feichtinger
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Sara Huber
- Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Johannes A. Mayr
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Barbara Kofler
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
- Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Daniel Neureiter
- Institute of Pathology, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Eckhard Klieser
- Institute of Pathology, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Sarah Hochmann
- Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University (PMU), 5020 Salzburg, Austria
| | - Wanda Lauth
- Department of Mathematics, Paris Lodron University, 5020 Salzburg, Austria
| | - Anna M. Schneider
- Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University (PMU), 5020 Salzburg, Austria
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29
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Tain YL, Hou CY, Chang-Chien GP, Lin S, Hsu CN. Perinatal Garlic Oil Supplementation Averts Rat Offspring Hypertension Programmed by Maternal Chronic Kidney Disease. Nutrients 2022; 14:4624. [PMID: 36364887 PMCID: PMC9657312 DOI: 10.3390/nu14214624] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 10/27/2022] [Accepted: 11/01/2022] [Indexed: 07/30/2023] Open
Abstract
Garlic (Allium sativum) is a functional food, having hydrogen sulfide (H2S)-releasing capacity, which exhibits considerable effects on hypertension and gut microbiota. H2S is strongly associated with hypertension and chronic kidney disease (CKD). Maternal CKD leads to hypertension in adult rat progeny, which was linked to disruption of the gut microbiota. This study validated the benefits of perinatal garlic oil supplementation against offspring hypertension induced by maternal CKD via modulation of H2S signaling, nitric oxide (NO), and the gut microbiota. Before pregnancy, female rats received a 0.5% adenine diet for 3 weeks to develop an animal model to mimic human CKD. Garlic oil (100 mg/kg/day) or vehicle was administered to pregnant rats by oral gavage during gestation and lactation. Perinatal garlic oil supplementation protected against maternal CKD-induced hypertension in offspring at 12 weeks of age. The beneficial effects of garlic oil are associated with enhanced H2S signaling, increased NO bioavailability, and shifts in gut microbiota. Perinatal garlic oil supplementation reduces abundance of genera Variovorax, Nocardia, Sphingomonas, and Rhodococcus. Our findings provide insight into the role of early H2S-targeted intervention as a preventive strategy in hypertension for further translational research.
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Affiliation(s)
- You-Lin Tain
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 330, Taiwan
| | - Chih-Yao Hou
- Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 811, Taiwan
| | - Guo-Ping Chang-Chien
- Institute of Environmental Toxin and Emerging-Contaminant, Cheng Shiu University, Kaohsiung 833, Taiwan
- Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung 833, Taiwan
- Super Micro Mass Research and Technology Center, Cheng Shiu University, Kaohsiung 833, Taiwan
| | - Sufan Lin
- Institute of Environmental Toxin and Emerging-Contaminant, Cheng Shiu University, Kaohsiung 833, Taiwan
- Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung 833, Taiwan
- Super Micro Mass Research and Technology Center, Cheng Shiu University, Kaohsiung 833, Taiwan
| | - Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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30
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Lajin B. Variability in Background Urinary Concentrations of the Hydrogen Sulfide Biomarker Thiosulfate. ACS OMEGA 2022; 7:38622-38626. [PMID: 36340101 PMCID: PMC9631904 DOI: 10.1021/acsomega.2c04112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 10/07/2022] [Indexed: 06/01/2023]
Abstract
Hydrogen sulfide is a toxic gas at high concentrations but has recently attracted attention as a naturally produced gaseous signaling molecule in various tissues of the human body, playing key physiological roles at low nanomolar concentrations. This has wide implications for chronic exposure to this gas in air at low levels far below toxicity. Thiosulfate is the currently used biomarker for exposure to hydrogen sulfide via inhalation but has been mainly employed for acute exposure. It is unknown how background thiosulfate concentrations vary on an intraindividual and interindividual basis in humans at normal ambient hydrogen sulfide levels (<1 μg m-3), which is key for the interpretation of its levels as biomarker for low-level hydrogen sulfide exposure. In the current work, the variability in thiosulfate urinary excretion in a total of 168 urine samples collected from eight volunteers over a period of 8 weeks was investigated. The determination of thiosulfate in urine was carried out by UHPLC-MS/MS. The total average concentration ± SD was 16 ± 6 μM (n = 168). Average urinary thiosulfate concentrations in the studied volunteers were within the range of 10-20 μM, but it was found that urinary thiosulfate can show significant day-to-day and week-to-week variability in some individuals (up to 10-fold), despite adjusting for urine specific gravity. In light of the presented variability data and previous studies about the lack of consistent response of thiosulfate to low levels of hydrogen sulfide inhalation exposure, and based on a review of the biochemistry of the production of thiosulfate and its various biological sources, it can be argued that thiosulfate might not be suitable as a biomarker for chronic environmental exposure to low levels of hydrogen sulfide via inhalation.
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Gáll T, Nagy P, Garai D, Potor L, Balla GJ, Balla G, Balla J. Overview on hydrogen sulfide-mediated suppression of vascular calcification and hemoglobin/heme-mediated vascular damage in atherosclerosis. Redox Biol 2022; 57:102504. [PMID: 36240620 PMCID: PMC9576974 DOI: 10.1016/j.redox.2022.102504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 10/06/2022] [Accepted: 10/07/2022] [Indexed: 12/04/2022] Open
Abstract
Vulnerable atherosclerotic plaques with hemorrhage considerably contribute to cardiovascular morbidity and mortality. Calcification is the main characteristic of advanced atherosclerotic lesions and calcified aortic valve disease (CAVD). Lyses of red blood cells and hemoglobin (Hb) release occur in human hemorrhagic complicated lesions. During the interaction of cell-free Hb with plaque constituents, Hb is oxidized to ferric and ferryl states accompanied by oxidative changes of the globin moieties and heme release. Accumulation of both ferryl-Hb and metHb has been observed in atherosclerotic plaques. The oxidation hotspots in the globin chain are the cysteine and tyrosine amino acids associated with the generation of Hb dimers, tetramers and polymers. Moreover, fragmentation of Hb occurs leading to the formation of globin-derived peptides. A series of these pro-atherogenic cellular responses can be suppressed by hydrogen sulfide (H2S). Since H2S has been explored to exhibit a wide range of physiologic functions to maintain vascular homeostasis, it is not surprising that H2S may play beneficial effects in the progression of atherosclerosis. In the present review, we summarize the findings about the effects of H2S on atherosclerosis and CAVD with a special emphasis on the oxidation of Hb/heme in atherosclerotic plaque development and vascular calcification.
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Affiliation(s)
- Tamás Gáll
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, 11003, University of Debrecen, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary
| | - Péter Nagy
- Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary; Institute of Oncochemistry, University of Debrecen, Hungary
| | - Dorottya Garai
- Department of Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary
| | - László Potor
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, 11003, University of Debrecen, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary
| | | | - György Balla
- Department of Pediatrics, Faculty of Medicine, University of Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, 11003, University of Debrecen, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary
| | - József Balla
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, 11003, University of Debrecen, Hungary; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary.
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Wolfson SJ, Hitchings R, Peregrina K, Cohen Z, Khan S, Yilmaz T, Malena M, Goluch ED, Augenlicht L, Kelly L. Bacterial hydrogen sulfide drives cryptic redox chemistry in gut microbial communities. Nat Metab 2022; 4:1260-1270. [PMID: 36266544 PMCID: PMC11328334 DOI: 10.1038/s42255-022-00656-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 09/07/2022] [Indexed: 01/20/2023]
Abstract
Microbial biochemistry contributes to a dynamic environment in the gut. Yet, how bacterial metabolites such as hydrogen sulfide (H2S) mechanistically alter the gut chemical landscape is poorly understood. Here we show that microbially generated H2S drives the abiotic reduction of azo (R-N = N-R') xenobiotics, which are commonly found in Western food dyes and drugs. This nonenzymatic reduction of azo compounds is demonstrated in Escherichia coli cultures, in human faecal microbial communities and in vivo in male mice. Changing dietary levels of the H2S xenobiotic redox partner Red 40 transiently decreases mouse faecal sulfide levels, demonstrating that a xenobiotic can attenuate sulfide concentration and alleviate H2S accumulation in vivo. Cryptic H2S redox chemistry thus can modulate sulfur homeostasis, alter the chemical landscape in the gut and contribute to azo food dye and drug metabolism. Interactions between chemicals derived from microbial communities may be a key feature shaping metabolism in the gut.
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Affiliation(s)
- Sarah J Wolfson
- Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Reese Hitchings
- Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Karina Peregrina
- Departments of Medicine and Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Ziv Cohen
- Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Saad Khan
- Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Tugba Yilmaz
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA
| | - Marcel Malena
- Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Edgar D Goluch
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA
| | - Leonard Augenlicht
- Departments of Medicine and Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Libusha Kelly
- Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
- Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
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Liu R, Shan Y, Xi S, Zhang X, Sun C. A deep-sea sulfate-reducing bacterium generates zero-valent sulfur via metabolizing thiosulfate. MLIFE 2022; 1:257-271. [PMID: 38818226 PMCID: PMC10989961 DOI: 10.1002/mlf2.12038] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 08/04/2022] [Accepted: 08/08/2022] [Indexed: 06/01/2024]
Abstract
Zero-valent sulfur (ZVS) is a crucial intermediate in the sulfur geobiochemical circulation and is widespread in deep-sea cold seeps. Sulfur-oxidizing bacteria are thought to be the major contributors to the formation of ZVS. However, ZVS production mediated by sulfate-reducing bacteria (SRB) has rarely been reported. In this study, we isolated and cultured a typical SRB designated Oceanidesulfovibrio marinus CS1 from deep-sea cold seep sediment in the South China Sea. We show that O. marinus CS1 forms ZVS in the medium supplemented with thiosulfate. Proteomic and protein activity assays revealed that thiosulfate reductase (PhsA) and the sulfide:quinone oxidoreductase (SQR) played key roles in driving ZVS formation in O. marinus CS1. During this process, thiosulfate firstly was reduced by PhsA to form sulfide, then sulfide was oxidized by SQR to produce ZVS. The expressions of PhsA and SQR were significantly upregulated when O. marinus CS1 was cultured in a deep-sea cold seep, strongly indicating that strain CS1 might form ZVS in the deep-sea environment. Notably, homologs of phsA and sqr were widely identified from microbes living in sediments of deep-sea cold seep in the South China Sea by the metagenomic analysis. We thus propose that SRB containing phsA and sqr genes potentially contribute to the formation of ZVS in deep-sea cold seep environments.
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Affiliation(s)
- Rui Liu
- CAS and Shandong Province Key Laboratory of Experimental Marine BiologyCenter of Deep Sea Research, Institute of Oceanology, Chinese Academy of SciencesQingdaoChina
- Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and TechnologyQingdaoChina
- Center of Ocean Mega‐Science, Chinese Academy of SciencesQingdaoChina
| | - Yeqi Shan
- CAS and Shandong Province Key Laboratory of Experimental Marine BiologyCenter of Deep Sea Research, Institute of Oceanology, Chinese Academy of SciencesQingdaoChina
- Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and TechnologyQingdaoChina
- Center of Ocean Mega‐Science, Chinese Academy of SciencesQingdaoChina
- College of Earth Science, University of Chinese Academy of SciencesBeijingChina
| | - Shichuan Xi
- Center of Ocean Mega‐Science, Chinese Academy of SciencesQingdaoChina
- College of Earth Science, University of Chinese Academy of SciencesBeijingChina
- CAS Key Laboratory of Marine Geology and EnvironmentCenter of Deep Sea Research, Institute of Oceanology, Chinese Academy of SciencesQingdaoChina
| | - Xin Zhang
- Center of Ocean Mega‐Science, Chinese Academy of SciencesQingdaoChina
- CAS Key Laboratory of Marine Geology and EnvironmentCenter of Deep Sea Research, Institute of Oceanology, Chinese Academy of SciencesQingdaoChina
| | - Chaomin Sun
- CAS and Shandong Province Key Laboratory of Experimental Marine BiologyCenter of Deep Sea Research, Institute of Oceanology, Chinese Academy of SciencesQingdaoChina
- Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and TechnologyQingdaoChina
- Center of Ocean Mega‐Science, Chinese Academy of SciencesQingdaoChina
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Reactive sulfur species and their significance in health and disease. Biosci Rep 2022; 42:231692. [PMID: 36039860 PMCID: PMC9484011 DOI: 10.1042/bsr20221006] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 08/23/2022] [Accepted: 08/25/2022] [Indexed: 11/23/2022] Open
Abstract
Reactive sulfur species (RSS) have been recognized in the last two decades as very important molecules in redox regulation. They are involved in metabolic processes and, in this way, they are responsible for maintenance of health. This review summarizes current information about the essential biological RSS, including H2S, low molecular weight persulfides, protein persulfides as well as organic and inorganic polysulfides, their synthesis, catabolism and chemical reactivity. Moreover, the role of RSS disturbances in various pathologies including vascular diseases, chronic kidney diseases, diabetes mellitus Type 2, neurological diseases, obesity, chronic obstructive pulmonary disease and in the most current problem of COVID-19 is presented. The significance of RSS in aging is also mentioned. Finally, the possibilities of using the precursors of various forms of RSS for therapeutic purposes are discussed.
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Xing C, Du Y, Duan T, Nim K, Chu J, Wang HY, Wang RF. Interaction between microbiota and immunity and its implication in colorectal cancer. Front Immunol 2022; 13:963819. [PMID: 35967333 PMCID: PMC9373904 DOI: 10.3389/fimmu.2022.963819] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/08/2022] [Indexed: 11/13/2022] Open
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the world. Besides genetic causes, colonic inflammation is one of the major risk factors for CRC development, which is synergistically regulated by multiple components, including innate and adaptive immune cells, cytokine signaling, and microbiota. The complex interaction between CRC and the gut microbiome has emerged as an important area of current CRC research. Metagenomic profiling has identified a number of prominent CRC-associated bacteria that are enriched in CRC patients, linking the microbiota composition to colitis and cancer development. Some microbiota species have been reported to promote colitis and CRC development in preclinical models, while a few others are identified as immune modulators to induce potent protective immunity against colitis and CRC. Mechanistically, microbiota regulates the activation of different immune cell populations, inflammation, and CRC via crosstalk between innate and adaptive immune signaling pathways, including nuclear factor kappa B (NF-κB), type I interferon, and inflammasome. In this review, we provide an overview of the potential interactions between gut microbiota and host immunity and how their crosstalk could synergistically regulate inflammation and CRC, thus highlighting the potential roles and mechanisms of gut microbiota in the development of microbiota-based therapies to prevent or alleviate colitis and CRC.
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Affiliation(s)
- Changsheng Xing
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Yang Du
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Tianhao Duan
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Kelly Nim
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Junjun Chu
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Helen Y. Wang
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Rong-Fu Wang
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
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Blachier F, Andriamihaja M, Kong XF. Fate of undigested proteins in the pig large intestine: What impact on the colon epithelium? ANIMAL NUTRITION 2022; 9:110-118. [PMID: 35573094 PMCID: PMC9065739 DOI: 10.1016/j.aninu.2021.08.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 08/03/2021] [Accepted: 08/03/2021] [Indexed: 11/21/2022]
Abstract
Apart from its obvious agronomic interest in feeding billions of people worldwide, the porcine species represents an irreplaceable experimental model for intestinal physiologists and nutritionists. In this review, we give an overview on the fate of proteins that are not fully digested in the pig small intestine, and thus are transferred into the large intestine. In the large intestine, dietary and endogenous proteins are converted to peptides and amino acids (AA) by the action of bacterial proteases and peptidases. AA, which cannot, except in the neonatal period, be absorbed to any significant level by the colonocytes, are used by the intestinal microbes for protein synthesis and for the production of numerous metabolites. Of note, the production of the AA-derived metabolites greatly depends on the amount of undigested polysaccharides in the pig's diet. The effects of these AA-derived bacterial metabolites on the pig colonic epithelium have not yet been largely studied. However, the available data, performed on colonic mucosa, isolated colonic crypts and colonocytes, indicate that some of them, like ammonia, butyrate, acetate, hydrogen sulfide (H2S), and p-cresol are active either directly or indirectly on energy metabolism in colonic epithelial cells. Further studies in that area will certainly gain from the utilization of the pig colonic organoid model, which allows for disposal of functional epithelial unities. Such studies will contribute to a better understanding of the potential causal links between diet-induced changes in the luminal concentrations of these AA-derived bacterial metabolites and effects on the colon epithelial barrier function and water/electrolyte absorption.
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Ni SJ, Yao ZY, Wei X, Heng X, Qu SY, Zhao X, Qi YY, Ge PY, Xu CP, Yang NY, Cao Y, Zhu HX, Guo R, Zhang QC. Vagus nerve stimulated by microbiota-derived hydrogen sulfide mediates the regulation of berberine on microglia in transient middle cerebral artery occlusion rats. Phytother Res 2022; 36:2964-2981. [PMID: 35583808 DOI: 10.1002/ptr.7490] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 03/08/2022] [Accepted: 04/19/2022] [Indexed: 11/05/2022]
Abstract
Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2 S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine-induced H2 S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c-fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota-dependent manner. H2 S stimulates the vagus nerve through TRPV1 is responsible for the berberine-induced gut-brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.
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Affiliation(s)
- Sai-Jia Ni
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zeng-Ying Yao
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaotong Wei
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xia Heng
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shu-Yue Qu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xin Zhao
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi-Yu Qi
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ping-Yuan Ge
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China
| | - Cai-Ping Xu
- Nanjing Sinolife Bio-tech Co., Ltd, Nanjing, China
| | - Nian-Yun Yang
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi Cao
- Institute of Literature in Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hua-Xu Zhu
- Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing, China
| | - Rui Guo
- School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Qi-Chun Zhang
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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Rodríguez-Romero JDJ, Durán-Castañeda AC, Cárdenas-Castro AP, Sánchez-Burgos JA, Zamora-Gasga VM, Sáyago-Ayerdi SG. What we know about protein gut metabolites: Implications and insights for human health and diseases. Food Chem X 2022; 13:100195. [PMID: 35499004 PMCID: PMC9039920 DOI: 10.1016/j.fochx.2021.100195] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/10/2021] [Accepted: 12/22/2021] [Indexed: 12/18/2022] Open
Abstract
Gut microbiota is a complex ecosystem of symbiotic bacteria that contribute to human metabolism and supply intestinal metabolites, whose production is mainly influenced by the diet. Dietary patterns characterized by a high intake of protein promotes the growth of proteolytic bacteria's, which produce metabolites from undigested protein fermentation. Microbioal protein metabolites can regulate immune, metabolic and neuronal responses in different target organs. Metabolic pathways of these compounds and their mechanisms of action on different pathologies can lead to the discovery of new diagnostic techniques, drugs and the potential use as functional ingredients in food. This review discusses the potential mechanisms by which amino acid catabolism is involved in microbial protein metabolites. In addition, results from several studies on the association of products from the intestinal metabolism of indigestible proteins and the state of health or disease of the host are revised.
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Affiliation(s)
- José de Jesús Rodríguez-Romero
- Tecnológico Nacional de México, Instituto Tecnológico de Tepic, Laboratorio Integral de Investigación en Alimentos, División de Estudios de Posgrado, Av. Tecnológico No 2595, Col. Lagos del Country CP 63175, Tepic, Nayarit, México
| | - Alba Cecilia Durán-Castañeda
- Tecnológico Nacional de México, Instituto Tecnológico de Tepic, Laboratorio Integral de Investigación en Alimentos, División de Estudios de Posgrado, Av. Tecnológico No 2595, Col. Lagos del Country CP 63175, Tepic, Nayarit, México
| | - Alicia Paulina Cárdenas-Castro
- Tecnológico Nacional de México, Instituto Tecnológico de Tepic, Laboratorio Integral de Investigación en Alimentos, División de Estudios de Posgrado, Av. Tecnológico No 2595, Col. Lagos del Country CP 63175, Tepic, Nayarit, México
| | - Jorge Alberto Sánchez-Burgos
- Tecnológico Nacional de México, Instituto Tecnológico de Tepic, Laboratorio Integral de Investigación en Alimentos, División de Estudios de Posgrado, Av. Tecnológico No 2595, Col. Lagos del Country CP 63175, Tepic, Nayarit, México
| | - Victor Manuel Zamora-Gasga
- Tecnológico Nacional de México, Instituto Tecnológico de Tepic, Laboratorio Integral de Investigación en Alimentos, División de Estudios de Posgrado, Av. Tecnológico No 2595, Col. Lagos del Country CP 63175, Tepic, Nayarit, México
| | - Sonia Guadalupe Sáyago-Ayerdi
- Tecnológico Nacional de México, Instituto Tecnológico de Tepic, Laboratorio Integral de Investigación en Alimentos, División de Estudios de Posgrado, Av. Tecnológico No 2595, Col. Lagos del Country CP 63175, Tepic, Nayarit, México
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Santana PT, Rosas SLB, Ribeiro BE, Marinho Y, de Souza HSP. Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets. Int J Mol Sci 2022; 23:3464. [PMID: 35408838 PMCID: PMC8998182 DOI: 10.3390/ijms23073464] [Citation(s) in RCA: 159] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/17/2022] [Accepted: 03/21/2022] [Indexed: 12/12/2022] Open
Abstract
Microbe-host communication is essential to maintain vital functions of a healthy host, and its disruption has been associated with several diseases, including Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD). Although individual members of the intestinal microbiota have been associated with experimental IBD, identifying microorganisms that affect disease susceptibility and phenotypes in humans remains a considerable challenge. Currently, the lack of a definition between what is healthy and what is a dysbiotic gut microbiome limits research. Nevertheless, although clear proof-of-concept of causality is still lacking, there is an increasingly evident need to understand the microbial basis of IBD at the microbial strain, genomic, epigenomic, and functional levels and in specific clinical contexts. Recent information on the role of diet and novel environmental risk factors affecting the gut microbiome has direct implications for the immune response that impacts the development of IBD. The complexity of IBD pathogenesis, involving multiple distinct elements, suggests the need for an integrative approach, likely utilizing computational modeling of molecular datasets to identify more specific therapeutic targets.
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Affiliation(s)
- Patricia Teixeira Santana
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
| | - Siane Lopes Bittencourt Rosas
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
| | - Beatriz Elias Ribeiro
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
| | - Ygor Marinho
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
| | - Heitor S. P. de Souza
- Department of Clinical Medicine, Federal University of Rio de Janeiro, Rio de Janeiro 21941-913, RJ, Brazil; (P.T.S.); (S.L.B.R.); (B.E.R.); (Y.M.)
- D’Or Institute for Research and Education (IDOR), Rua Diniz Cordeiro 30, Botafogo, Rio de Janeiro 22281-100, RJ, Brazil
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40
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Murros KE. Hydrogen Sulfide Produced by Gut Bacteria May Induce Parkinson's Disease. Cells 2022; 11:978. [PMID: 35326429 PMCID: PMC8946538 DOI: 10.3390/cells11060978] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 03/01/2022] [Accepted: 03/10/2022] [Indexed: 12/24/2022] Open
Abstract
Several bacterial species can generate hydrogen sulfide (H2S). Study evidence favors the view that the microbiome of the colon harbors increased amounts of H2S producing bacteria in Parkinson's disease. Additionally, H2S can easily penetrate cell membranes and enter the cell interior. In the cells, excessive amounts of H2S can potentially release cytochrome c protein from the mitochondria, increase the iron content of the cytosolic iron pool, and increase the amount of reactive oxygen species. These events can lead to the formation of alpha-synuclein oligomers and fibrils in cells containing the alpha-synuclein protein. In addition, bacterially produced H2S can interfere with the body urate metabolism and affect the blood erythrocytes and lymphocytes. Gut bacteria responsible for increased H2S production, especially the mucus-associated species of the bacterial genera belonging to the Desulfovibrionaceae and Enterobacteriaceae families, are likely play a role in the pathogenesis of Parkinson's disease. Special attention should be devoted to changes not only in the colonic but also in the duodenal microbiome composition with regard to the pathogenesis of Parkinson's disease. Influenza infections may increase the risk of Parkinson's disease by causing the overgrowth of H2S-producing bacteria both in the colon and duodenum.
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Affiliation(s)
- Kari Erik Murros
- Institute of Clinical Medicine, University of Eastern Finland (UEF), 70211 Kuopio, Finland
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Bouillaud F. Sulfide Oxidation Evidences the Immediate Cellular Response to a Decrease in the Mitochondrial ATP/O2 Ratio. Biomolecules 2022; 12:biom12030361. [PMID: 35327553 PMCID: PMC8944965 DOI: 10.3390/biom12030361] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 02/16/2022] [Accepted: 02/16/2022] [Indexed: 11/25/2022] Open
Abstract
The present article will not attempt to deal with sulfide per se as a signaling molecule but will aim to examine the consequences of sulfide oxidation by mitochondrial sulfide quinone reductase in mammalian cells. This oxidation appears first as a priority to avoid self-poisoning by endogenous sulfide and second to occur with the lowest ATP/O2 ratio when compared to other mitochondrial substrates. This is explained by the injection of electrons in the respiratory chain after complex I (as for succinate) and by a sulfur oxidation step implying a dioxygenase that consumes oxygen but does not contribute to mitochondrial bioenergetics. Both contribute to increase cellular oxygen consumption if sulfide is provided below its toxic level (low µM). Accordingly, if oxygen supply or respiratory chain activity becomes a limiting factor, small variations in sulfide release impact the cellular ATP/ADP ratio, a major metabolic sensor.
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Affiliation(s)
- Frédéric Bouillaud
- Institut Cochin, INSERM, CNRS, Université de Paris, F75014 Paris, France
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42
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Chen M, Zhu JY, Mu WJ, Guo L. Cysteine dioxygenase type 1 (CDO1): its functional role in physiological and pathophysiological processes. Genes Dis 2022. [DOI: 10.1016/j.gendis.2021.12.023] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Zhu J, Yang G. H 2S signaling and extracellular matrix remodeling in cardiovascular diseases: A tale of tense relationship. Nitric Oxide 2021; 116:14-26. [PMID: 34428564 DOI: 10.1016/j.niox.2021.08.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 08/16/2021] [Accepted: 08/18/2021] [Indexed: 12/12/2022]
Abstract
Extracellular matrix (ECM) is a non-cellular three-dimensional macromolecular network that not only provides mechanical support but also transduces essential molecular signals in organ functions. ECM is constantly remodeled to control tissue homeostasis, responsible for cell adhesion, cell migration, cell-to-cell communication, and cell differentiation, etc. The dysregulation of ECM components contributes to various diseases, including cardiovascular diseases, fibrosis, cancer, and neurodegenerative diseases, etc. Aberrant ECM remodeling is initiated by various stress, such as oxidative stress, inflammation, ischemia, and mechanical stress, etc. Hydrogen sulfide (H2S) is a gasotransmitter that exhibits a wide variety of cytoprotective and physiological functions through its anti-oxidative and anti-inflammatory actions. Amounting research shows that H2S can attenuate aberrant ECM remodeling. In this review, we discussed the implications and mechanisms of H2S in the regulation of ECM remodeling in cardiovascular diseases, and highlighted the potential of H2S in the prevention and treatment of cardiovascular diseases through attenuating adverse ECM remodeling.
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Affiliation(s)
- Jiechun Zhu
- School of Biological, Chemical & Forensic Sciences, Laurentian University, Sudbury, Canada; Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Canada
| | - Guangdong Yang
- School of Biological, Chemical & Forensic Sciences, Laurentian University, Sudbury, Canada; Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Canada.
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Sultan S, El-Mowafy M, Elgaml A, Ahmed TAE, Hassan H, Mottawea W. Metabolic Influences of Gut Microbiota Dysbiosis on Inflammatory Bowel Disease. Front Physiol 2021; 12:715506. [PMID: 34646151 PMCID: PMC8502967 DOI: 10.3389/fphys.2021.715506] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 08/18/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic medical disorders characterized by recurrent gastrointestinal inflammation. While the etiology of IBD is still unknown, the pathogenesis of the disease results from perturbations in both gut microbiota and the host immune system. Gut microbiota dysbiosis in IBD is characterized by depleted diversity, reduced abundance of short chain fatty acids (SCFAs) producers and enriched proinflammatory microbes such as adherent/invasive E. coli and H2S producers. This dysbiosis may contribute to the inflammation through affecting either the immune system or a metabolic pathway. The immune responses to gut microbiota in IBD are extensively discussed. In this review, we highlight the main metabolic pathways that regulate the host-microbiota interaction. We also discuss the reported findings indicating that the microbial dysbiosis during IBD has a potential metabolic impact on colonocytes and this may underlie the disease progression. Moreover, we present the host metabolic defectiveness that adds to the impact of symbiont dysbiosis on the disease progression. This will raise the possibility that gut microbiota dysbiosis associated with IBD results in functional perturbations of host-microbiota interactions, and consequently modulates the disease development. Finally, we shed light on the possible therapeutic approaches of IBD through targeting gut microbiome.
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Affiliation(s)
- Salma Sultan
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada
| | - Mohammed El-Mowafy
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Abdelaziz Elgaml
- Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.,Department of Microbiology and Immunology, Faculty of Pharmacy, Horus University, New Damietta, Egypt
| | - Tamer A E Ahmed
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.,Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Hebatoallah Hassan
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.,Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt
| | - Walid Mottawea
- Faculty of Health Sciences, School of Nutrition Sciences, University of Ottawa, Ottawa, ON, Canada.,Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
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Raimondi S, Calvini R, Candeliere F, Leonardi A, Ulrici A, Rossi M, Amaretti A. Multivariate Analysis in Microbiome Description: Correlation of Human Gut Protein Degraders, Metabolites, and Predicted Metabolic Functions. Front Microbiol 2021; 12:723479. [PMID: 34603248 PMCID: PMC8484906 DOI: 10.3389/fmicb.2021.723479] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/20/2021] [Indexed: 01/01/2023] Open
Abstract
Protein catabolism by intestinal bacteria is infamous for releasing many harmful compounds, negatively affecting the health status, both locally and systemically. In a previous study, we enriched in protein degraders the fecal microbiota of five subjects, utilizing a medium containing protein and peptides as sole fermentable substrates and we monitored their evolution by 16S rRNA gene profiling. In the present study, we fused the microbiome data and the data obtained by the analysis of the volatile organic compounds (VOCs) in the headspace of the cultures. Then, we utilized ANOVA simultaneous component analysis (ASCA) to establish a relationship between metabolites and bacteria. In particular, ASCA allowed to separately assess the effect of subject, time, inoculum concentration, and their binary interactions on both microbiome and volatilome data. All the ASCA submodels pointed out a consistent association between indole and Escherichia–Shigella, and the relationship of butyric, 3-methyl butanoic, and benzenepropanoic acids with some bacterial taxa that were major determinants of cultures at 6 h, such as Lachnoclostridiaceae (Lachnoclostridium), Clostridiaceae (Clostridium sensu stricto), and Sutterellaceae (Sutterella and Parasutterella). The metagenome reconstruction with PICRUSt2 and its functional annotation indicated that enrichment in a protein-based medium affected the richness and diversity of functional profiles, in the face of a decrease of richness and evenness of the microbial community. Linear discriminant analysis (LDA) effect size indicated a positive differential abundance (p < 0.05) for the modules of amino acid catabolism that may be at the basis of the changes of VOC profile. In particular, predicted genes encoding functions belonging to the superpathways of ornithine, arginine, and putrescine transformation to GABA and eventually to succinyl-CoA, of methionine degradation, and various routes of breakdown of aromatic compounds yielding succinyl-CoA or acetyl-CoA became significantly more abundant in the metagenome of the bacterial community.
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Affiliation(s)
- Stefano Raimondi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Rosalba Calvini
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Francesco Candeliere
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Alan Leonardi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandro Ulrici
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.,BIOGEST-SITEIA, University of Modena and Reggio Emilia, Modena, Italy
| | - Maddalena Rossi
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.,BIOGEST-SITEIA, University of Modena and Reggio Emilia, Modena, Italy
| | - Alberto Amaretti
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.,BIOGEST-SITEIA, University of Modena and Reggio Emilia, Modena, Italy
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Tomasova L, Grman M, Ondrias K, Ufnal M. The impact of gut microbiota metabolites on cellular bioenergetics and cardiometabolic health. Nutr Metab (Lond) 2021; 18:72. [PMID: 34266472 PMCID: PMC8281717 DOI: 10.1186/s12986-021-00598-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 07/02/2021] [Indexed: 12/20/2022] Open
Abstract
Recent research demonstrates a reciprocal relationship between gut microbiota-derived metabolites and the host in controlling the energy homeostasis in mammals. On the one hand, to thrive, gut bacteria exploit nutrients digested by the host. On the other hand, the host utilizes numerous products of gut bacteria metabolism as a substrate for ATP production in the colon. Finally, bacterial metabolites seep from the gut into the bloodstream and interfere with the host’s cellular bioenergetics machinery. Notably, there is an association between alterations in microbiota composition and the development of metabolic diseases and their cardiovascular complications. Some metabolites, like short-chain fatty acids and trimethylamine, are considered markers of cardiometabolic health. Others, like hydrogen sulfide and nitrite, demonstrate antihypertensive properties. Scientific databases were searched for pre-clinical and clinical studies to summarize current knowledge on the role of gut microbiota metabolites in the regulation of mammalian bioenergetics and discuss their potential involvement in the development of cardiometabolic disorders. Overall, the available data demonstrates that gut bacteria products affect physiological and pathological processes controlling energy and vascular homeostasis. Thus, the modulation of microbiota-derived metabolites may represent a new approach for treating obesity, hypertension and type 2 diabetes.
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Affiliation(s)
- Lenka Tomasova
- Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovak Republic.
| | - Marian Grman
- Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovak Republic
| | - Karol Ondrias
- Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Dubravska cesta 9, 845 05, Bratislava, Slovak Republic
| | - Marcin Ufnal
- Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 02-091, Warsaw, Poland.
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Mayorga EJ, Horst EA, Al-Qaisi M, Goetz BM, Abeyta MA, Rodríguez-Jiménez S, Lei S, Acosta JA, Patience JF, Serao MCR, Baumgard LH. Effects of continuously infusing glucose or casein into the terminal ileum on biomarkers of metabolism, inflammation, and intestinal morphology in growing pigs. J Anim Sci 2021; 99:skab163. [PMID: 34015122 PMCID: PMC8280934 DOI: 10.1093/jas/skab163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 05/17/2021] [Indexed: 12/23/2022] Open
Abstract
Study objectives were to determine the effects of continuously infusing glucose (GLC) or casein (CAS) into the terminal ileum on biomarkers of metabolism, inflammation, and intestinal morphology in growing pigs. Crossbred gilts (n = 19; 81 ± 3 kg body weight [BW]) previously fitted with T-cannulas at terminal ileum were used in the current experiment. Following 4 d of acclimation, pigs were enrolled in 2 experimental 4-d periods (P). During P1, pigs were housed in individual pens and fed ad libitum for collection of baseline parameters. At the beginning of P2, pigs were assigned to 1 of 3 infusion treatments: 1) control (CON; water; 3 liters/d; n = 7), 2) GLC (dextrose 50%; 500 g/d; n = 6;), or 3) CAS (casein sodium salt; 300 g/d; n = 6). Water, GLC, and CAS solutions were continuously infused at a rate of 125 mL/h for the entirety of P2. Animals were euthanized at the end of P2, and intestinal tissue was collected. During P2, average daily feed intake differed across treatments and was reduced in GLC compared with CON pigs (14%), while CAS pigs consumed an intermediate amount (P = 0.05). Average daily gain and final BW were similar across treatments. A treatment by time interaction was observed for blood urea nitrogen (BUN; P < 0.01), as it decreased in GLC (21%) while it gradually increased in CAS (76%) pigs relative to CON pigs. Mild hyperthermia occurred with both GLC and CAS infusions relative to CON (+0.3 and 0.2 °C, respectively; P < 0.01). Blood neutrophils increased in CAS relative to CON pigs (26%) but remained similar between CON and GLC treatments (P < 0.01). Blood monocytes decreased in GLC relative to CON pigs (24%) while CAS pigs had an intermediate value (P = 0.03). Circulating lipopolysaccharide binding protein tended to decrease in GLC (29%) relative to CON pigs but remained similar between CON and CAS pigs (P = 0.10). Plasma tumor necrosis factor-alpha was similar across treatments. Ileum villus height:crypt depth was increased in CAS compared with CON pigs (33%; P = 0.05) while GLC pigs had an intermediate value. Colon myeloperoxidase-stained area increased in CAS compared with CON pigs (45%; P = 0.03) but remained similar between GLC and CON pigs. In summary, continuously infusing GLC or CAS into the terminal ileum appeared to stimulate a mild immune response and differently altered BUN patterns but had little or no effects on blood inflammatory markers, intestinal morphology, or key production parameters.
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Affiliation(s)
- Edith J Mayorga
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
| | - Erin A Horst
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
| | - Mohmmad Al-Qaisi
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
| | - Brady M Goetz
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
| | - Megan A Abeyta
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
| | | | - Samantha Lei
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
| | - Jesus A Acosta
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
| | - John F Patience
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
| | | | - Lance H Baumgard
- Department of Animal Science, Iowa State University, Ames, IA 50011, USA
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Rose P, Moore PK, Whiteman M, Kirk C, Zhu YZ. Diet and Hydrogen Sulfide Production in Mammals. Antioxid Redox Signal 2021; 34:1378-1393. [PMID: 33372834 DOI: 10.1089/ars.2020.8217] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Significance: In recent times, it has emerged that some dietary sulfur compounds can act on mammalian cell signaling systems via their propensity to release hydrogen sulfide (H2S). H2S plays important biochemical and physiological roles in the heart, gastrointestinal tract, brain, kidney, and immune systems of mammals. Reduced levels of H2S in cells and tissues correlate with a spectrum of pathophysiological conditions, including heart disease, diabetes, obesity, and altered immune function. Recent Advances: In the last decade, researchers have now begun to explore the mechanisms by which dietary-derived sulfur compounds, in addition to cysteine, can act as sources of H2S. This research has led to the identified several compounds, organic sulfides, isothiocyanates, and inorganic sulfur species including sulfate that can act as potential sources of H2S in mammalian cells and tissues. Critical Issues: We have summarised progress made in the identification of dietary factors that can impact on endogenous H2S levels in mammals. We also describe current research focused on how some sulfur molecules present in dietary plants, and associated chemical analogues, act as sources of H2S, and discuss the biological properties of these molecules as studied in a range of in vitro and in vivo systems. Future Directions: The identification of sulfur compounds in edible plants that can act as novel H2S releasing molecules is intriguing. Research in this area could inform future studies exploring the impact of diet on H2S levels in mammalian systems. Despite recent progress, additional work is needed to determine the mechanisms by which H2S is released from these molecules following ingestions of dietary plants in humans, whether the amounts of H2S produced is of physiological significance following the metabolism of these compounds in vivo, and if diet could be used to manipulated H2S levels in humans. Importantly, this will lead to a better understanding of the biological significance of H2S generated from dietary sources, and this information could be used in the development of plant breeding initiatives to increase the levels of H2S releasing sulfur compounds in crops, or inform dietary intervention strategies that could be used to alter the levels of H2S in humans.
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Affiliation(s)
- Peter Rose
- School of Biosciences, University of Nottingham, Loughborough, Leicestershire, United Kingdom.,State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau, China
| | - Philip Keith Moore
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Matthew Whiteman
- College of Medicine and Health, University of Exeter Medical School, Exeter, United Kingdom
| | - Charlotte Kirk
- School of Biosciences, University of Nottingham, Loughborough, Leicestershire, United Kingdom
| | - Yi-Zhun Zhu
- State Key Laboratory of Quality Research in Chinese Medicine, School of Pharmacy, Macau University of Science and Technology, Macau, China
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Wellington MO, Agyekum AK, Van Kessel AG. Microbial sensing in the neonatal pig gut: effect of diet-independent and diet-dependent factors 1. CANADIAN JOURNAL OF ANIMAL SCIENCE 2021. [DOI: 10.1139/cjas-2020-0051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
There is considerable agreement that the gastrointestinal microbiota contributes to the performance and health of the neonate, and this relationship includes an ability of the host animal to “sense” changes in the microbial community. Identifying the mechanisms used by the host to sense microbiota is one approach to developing methods to manipulate the microbiota to improve pig health and performance. Diet-independent microbial products are molecules unique to the microbial community and sensed by host pattern recognition receptors stimulating inflammation. Common among all members of the microbial community, their presence is unaffected by diet, but the nature of the response does depends on factors affecting the microenvironment in which the molecule is detected. Diet-dependent microbial products arise as products of fermentation of dietary components and include short-chain fatty acids, ammonia, phenols, hydrogen sulfide, amines, and many other compounds. A plethora of sensing mechanisms exists that include enzymatic metabolism as well as membrane receptors that have evolved to respond to microbial products (e.g., short-chain fatty acid receptors), or simply cross-react with microbial products. This review focuses on host mechanisms used to sense the intestinal microbiota and attempts to establish practical considerations for neonatal gut health based on current understanding.
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Affiliation(s)
- Michael O. Wellington
- Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
| | - Atta K. Agyekum
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 3, DK-1870, Frederiksberg C, Denmark
| | - Andrew G. Van Kessel
- Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon, SK S7N 5A8, Canada
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