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Rezaie A, Chang BW, de Freitas Germano J, Leite G, Mathur R, Houser K, Hosseini A, Brimberry D, Rashid M, Mehravar S, Villanueva-Millan MJ, Sanchez M, Weitsman S, Fajardo CM, Rivera IG, Joo L, Chan Y, Barlow GM, Pimentel M. Effect, Tolerability, and Safety of Exclusive Palatable Elemental Diet in Patients with Intestinal Microbial Overgrowth. Clin Gastroenterol Hepatol 2025:S1542-3565(25)00241-1. [PMID: 40189034 DOI: 10.1016/j.cgh.2025.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/18/2025] [Accepted: 03/12/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND & AIMS Elemental diets (EDs) have desirable safety and efficacy profiles in several clinical settings partly because of modulation of gut microbiome. Palatability of EDs remains the main barrier to compliance/adherence, and their effect has not been prospectively explored in microbiome-driven disorders, such as small intestinal bacterial overgrowth (SIBO) and intestinal methanogen overgrowth (IMO). We aimed to assess the effect, tolerance, and safety of a novel palatable ED (PED) in subjects with IMO and/or SIBO. METHODS Adult subjects with positive lactulose breath tests for SIBO and/or IMO completed 1 week of screening, 2 weeks of exclusive oral PED, and 2 weeks of follow-up during reintroduction of regular diet. Primary end point was changes in stool microbiome after PED and reintroduction of regular diet. Secondary end points included tolerability, rate of normalization of lactulose breath tests, change in stool form based on daily diary and artificial intelligence-analyzed images, symptomatic response, and adverse events. RESULTS All 30 enrolled subjects tolerated the PED and completed the trial. Several taxonomic differences were detected including decreased relative abundance of Prevotella_9 and Fusobacterium. Abundance of Methanobrevibacter smithii decreased at the end of the trial and correlated with average daily methane levels (P = .024; r = 0.489). Maximum methane levels (41 ± 35 to 12 ± 15 ppm; P < .001) and hydrogen rise (43 ± 42 to 12 ± 11 ppm; P < .001) dropped significantly, with 73% normalizing their lactulose breath tests. Adequate global relief of symptoms was reported in 83% of subjects. No serious or severe adverse events were observed. CONCLUSIONS PED significantly impacts the gut microbiome. Tolerance to EDs improves with enhanced palatability. Larger studies with longer follow-up are needed to assess response durability. (ClinicalTrials.gov ID: NCT05978973).
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Affiliation(s)
- Ali Rezaie
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, California.
| | - Bianca W Chang
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, California
| | | | - Gabriela Leite
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Ruchi Mathur
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai, Los Angeles, California
| | | | - Ava Hosseini
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Daniel Brimberry
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Mohamad Rashid
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Sepideh Mehravar
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | | | - Maritza Sanchez
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Stacy Weitsman
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Cristina M Fajardo
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Ignacio G Rivera
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Lijin Joo
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Yin Chan
- Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, California
| | - Gillian M Barlow
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California
| | - Mark Pimentel
- Medically Associated Science and Technology (MAST) Program, Cedars-Sinai, Los Angeles, California; Karsh Division of Gastroenterology and Hepatology, Department of Medicine, Cedars-Sinai, Los Angeles, California
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Xu X, Fu H, Quan H, Li Y, Chen Q, Qu D, Pi X. Effects of fructooligosaccharides and Lactobacillus reuteri on the composition and metabolism of gut microbiota in students. Food Funct 2025; 16:1562-1575. [PMID: 39912125 DOI: 10.1039/d4fo03763d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2025]
Abstract
Fructooligosaccharides (FOSs) and Lactobacillus reuteri have shown great potential in treating gastrointestinal diseases by regulating gut microbiota and metabolites. However, the synergistic effect between these two remains unclear. In this study, an in vitro fermentation model was constructed to investigate the regulatory effects of FOSs and L. reuteri on the gut microbiota of healthy student populations. After 24 hours of fecal fermentation, the results indicated that the experimental group added with FOSs had increased relative abundances of Bifidobacterium and Lactobacillus, while it exhibited lower relative abundances of Escherichia-Shigella and Bacteroides. Conversely, the groups added with L. reuteri had higher relative abundances of Bacillus and unclassified_c_Bacilli. The results of microbial metabolism revealed that the addition of FOSs produced a large amount of acetic acid, but reduced the contents of propionic acid, butyric acid, isobutyric acid, and isovaleric acid, along with reducing the production of H2, H2S and NH3. In contrast, the addition of L. reuteri had no significant effect on metabolism. Compared to the single additions, the combination of FOSs and L. reuteri had its advantages and had a more balanced microbial structure and metabolic regulation similar to the addition of FOSs alone. Additionally, correlation analysis revealed a negative correlation between gas production and Bifidobacterium, Lactobacillus, and Bacillus, and a positive correlation with Escherichia-Shigella and Bacteroides. Moreover, the formation of acetic acid was positively correlated with Bifidobacterium and negatively correlated with Escherichia-Shigella. These findings demonstrated that the combination of FOSs and L. reuteri can effectively synergistically regulate the fecal microbiome of students. This study can provide a theoretical reference for the precise development of functional foods. However, the regulatory mechanisms need further in-depth investigation.
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Affiliation(s)
- Xu Xu
- Food Safety Key Laboratory of Zhejiang Province, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, PR China.
- Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China.
| | - Hao Fu
- Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China.
| | - Huihui Quan
- Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China.
| | - Yan Li
- Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China.
| | - Qiaoyun Chen
- Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China.
| | - Daofeng Qu
- Food Safety Key Laboratory of Zhejiang Province, School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou 310018, PR China.
| | - Xionge Pi
- Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China.
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Gobert AP, Latour YL, McNamara KM, Hawkins CV, Williams KJ, Asim M, Barry DP, Allaman MM, Delgado AG, Milne GL, Zhao S, Piazuelo MB, Washington MK, Coburn LA, Wilson KT. The reverse transsulfuration pathway affects the colonic microbiota and contributes to colitis in mice. Amino Acids 2024; 56:63. [PMID: 39427081 PMCID: PMC11490428 DOI: 10.1007/s00726-024-03423-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 10/05/2024] [Indexed: 10/21/2024]
Abstract
Cystathionine γ-lyase (CTH) is a critical enzyme in the reverse transsulfuration pathway, the major route for the metabolism of sulfur-containing amino acids, notably converting cystathionine to cysteine. We reported that CTH supports gastritis induced by the pathogen Helicobacter pylori. Herein our aim was to investigate the role of CTH in colonic inflammation. First, we found that CTH is induced in the colon mucosa in mice with dextran sulfate sodium-induced colitis. Expression of CTH was completely absent in the colon of Cth-/- mice. We observed that clinical and histological parameters are ameliorated in Cth-deficient mice compared to wild-type animals. However, Cth deletion had no effect on tumorigenesis and the level of dysplasia in mice treated with azoxymethane-DSS, as a reliable model of colitis-associated carcinogenesis. Mechanistically, we determined that the deletion of the gene Slc7a11 encoding for solute carrier family 7 member 11, the transporter of the anionic form of cysteine, does not affect DSS colitis. Lastly, we found that the richness and diversity of the fecal microbiota were significantly increased in Cth-/- mice compared to both WT and Slc7a11-/- mice. In conclusion, our data suggest that the enzyme CTH represents a target for clinical intervention in patients with inflammatory bowel disease, potentially by beneficially reshaping the composition of the gut microbiota.
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Affiliation(s)
- Alain P Gobert
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Yvonne L Latour
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Kara M McNamara
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Caroline V Hawkins
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Kamery J Williams
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Mohammad Asim
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Daniel P Barry
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Margaret M Allaman
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Alberto G Delgado
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Ginger L Milne
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Shilin Zhao
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - M Blanca Piazuelo
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - M Kay Washington
- Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Lori A Coburn
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, 37232, USA
| | - Keith T Wilson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
- Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
- Program in Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, 37232, USA.
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Kim HS, Oh SJ, Kim BK, Kim JE, Kim BH, Park YK, Yang BG, Lee JY, Bae JW, Lee CK. Dysbiotic signatures and diagnostic potential of gut microbial markers for inflammatory bowel disease in Korean population. Sci Rep 2024; 14:23701. [PMID: 39390011 PMCID: PMC11467411 DOI: 10.1038/s41598-024-74002-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 09/23/2024] [Indexed: 10/12/2024] Open
Abstract
Fecal samples were collected from 640 individuals in Korea, including 523 patients with IBD (223 with Crohn's disease [CD] and 300 with ulcerative colitis [UC]) and 117 healthy controls. The samples were subjected to cross-sectional gut metagenomic analysis using 16 S rRNA sequencing and bioinformatics analysis. Patients with IBD, particularly those with CD, exhibited significantly lower alpha diversities than the healthy subjects. Differential abundance analysis revealed dysbiotic signatures, characterized by an expansion of the genus Escherichia-Shigella in patients with CD. Functional annotations showed that functional pathways related to bacterial pathogenesis and production of hydrogen sulfide (H2S) were strongly upregulated in patients with CD. A dysbiosis score, calculated based on functional characteristics, highly correlated with disease severity. Markers distinguishing between healthy subjects and patients with IBD showed accurate classification based on a small number of microbial taxa, which may be used to diagnose ambiguous cases. These findings confirm the taxonomic and functional dysbiosis of the gut microbiota in patients with IBD, especially those with CD. Taxa indicative of dysbiosis may have significant implications for future clinical research on the management and diagnosis of IBD.
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Affiliation(s)
- Hyun Sik Kim
- Department of Biology, Kyung Hee University, Seoul, Republic of Korea
| | - Shin Ju Oh
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Byung Kwon Kim
- Research Institute, GI Biome Inc., Seongnam, Republic of Korea
| | - Ji Eun Kim
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea
| | - Bo-Hyung Kim
- Department of Clinical Pharmacology and Therapeutics, Kyung Hee University Hospital, Seoul, Republic of Korea
- East-West Medical Research Institute, Kyung Hee University, Seoul, Republic of Korea
| | - Young-Kyu Park
- Research Institute, GI Biome Inc., Seongnam, Republic of Korea
| | - Bo-Gie Yang
- Research Institute, GI Biome Inc., Seongnam, Republic of Korea
| | - Jae-Yun Lee
- Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea
| | - Jin-Woo Bae
- Department of Biology, Kyung Hee University, Seoul, Republic of Korea.
- Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
- Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Republic of Korea.
| | - Chang Kyun Lee
- Department of Gastroenterology, Center for Crohn's and Colitis, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
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Singh SB, Braun CA, Carroll-Portillo A, Coffman CN, Lin HC. Sulfate-Reducing Bacteria Induce Pro-Inflammatory TNF-α and iNOS via PI3K/Akt Pathway in a TLR 2-Dependent Manner. Microorganisms 2024; 12:1833. [PMID: 39338507 PMCID: PMC11434237 DOI: 10.3390/microorganisms12091833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 08/31/2024] [Accepted: 09/02/2024] [Indexed: 09/30/2024] Open
Abstract
Desulfovibrio, resident gut sulfate-reducing bacteria (SRB), are found to overgrow in diseases such as inflammatory bowel disease and Parkinson's disease. They activate a pro-inflammatory response, suggesting that Desulfovibrio may play a causal role in inflammation. Class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway regulates key events in the inflammatory response to infection. Dysfunctional PI3K/Akt signaling is linked to numerous diseases. Bacterial-induced PI3K/Akt pathway may be activated downstream of toll-like receptor (TLR) signaling. Here, we tested the hypothesis that Desulfovibrio vulgaris (DSV) may induce tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) expression via PI3K/Akt in a TLR 2-dependent manner. RAW 264.7 macrophages were infected with DSV, and protein expression of p-Akt, p-p70S6K, p-NF-κB, p-IkB, TNF-α, and iNOS was measured. We found that DSV induced these proteins in a time-dependent manner. Heat-killed and live DSV, but not bacterial culture supernatant or a probiotic Lactobacillus plantarum, significantly caused PI3K/AKT/TNF/iNOS activation. LY294002, a PI3K/Akt signaling inhibitor, and TL2-C29, a TLR 2 antagonist, inhibited DSV-induced PI3K/AKT pathway. Thus, DSV induces pro-inflammatory TNF-α and iNOS via PI3K/Akt pathway in a TLR 2-dependent manner. Taken together, our study identifies a novel mechanism by which SRB such as Desulfovibrio may trigger inflammation in diseases associated with SRB overgrowth.
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Affiliation(s)
- Sudha B Singh
- Biomedical Research Institute of New Mexico, New Mexico Veterans Affairs (VA) Health Care System, 1501 San Pedro Dr. SE, Albuquerque, NM 87108, USA
| | - Cody A Braun
- Biomedical Research Institute of New Mexico, New Mexico Veterans Affairs (VA) Health Care System, 1501 San Pedro Dr. SE, Albuquerque, NM 87108, USA
| | - Amanda Carroll-Portillo
- Division of Gastroenterology and Hepatology, Department of Medicine, University of New Mexico, Albuquerque, NM 87131, USA
| | - Cristina N Coffman
- Biomedical Research Institute of New Mexico, New Mexico Veterans Affairs (VA) Health Care System, 1501 San Pedro Dr. SE, Albuquerque, NM 87108, USA
| | - Henry C Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, University of New Mexico, Albuquerque, NM 87131, USA
- Medicine Service, New Mexico Veterans Affairs (VA) Health Care System, 1501 San Pedro Dr. SE, Albuquerque, NM 87108, USA
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Luo W, Zhao M, Dwidar M, Gao Y, Xiang L, Wu X, Medema MH, Xu S, Li X, Schäfer H, Chen M, Feng R, Zhu Y. Microbial assimilatory sulfate reduction-mediated H 2S: an overlooked role in Crohn's disease development. MICROBIOME 2024; 12:152. [PMID: 39152482 PMCID: PMC11328384 DOI: 10.1186/s40168-024-01873-2] [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: 03/27/2024] [Accepted: 07/13/2024] [Indexed: 08/19/2024]
Abstract
BACKGROUND H2S imbalances in the intestinal tract trigger Crohn's disease (CD), a chronic inflammatory gastrointestinal disorder characterized by microbiota dysbiosis and barrier dysfunction. However, a comprehensive understanding of H2S generation in the gut, and the contributions of both microbiota and host to systemic H2S levels in CD, remain to be elucidated. This investigation aimed to enhance comprehension regarding the sulfidogenic potential of both the human host and the gut microbiota. RESULTS Our analysis of a treatment-naive CD cohorts' fecal metagenomic and biopsy metatranscriptomic data revealed reduced expression of host endogenous H2S generation genes alongside increased abundance of microbial exogenous H2S production genes in correlation with CD. While prior studies focused on microbial H2S production via dissimilatory sulfite reductases, our metagenomic analysis suggests the assimilatory sulfate reduction (ASR) pathway is a more significant contributor in the human gut, given its high prevalence and abundance. Subsequently, we validated our hypothesis experimentally by generating ASR-deficient E. coli mutants ∆cysJ and ∆cysM through the deletion of sulfite reductase and L-cysteine synthase genes. This alteration significantly affected bacterial sulfidogenic capacity, colon epithelial cell viability, and colonic mucin sulfation, ultimately leading to colitis in murine model. Further study revealed that gut microbiota degrade sulfopolysaccharides and assimilate sulfate to produce H2S via the ASR pathway, highlighting the role of sulfopolysaccharides in colitis and cautioning against their use as food additives. CONCLUSIONS Our study significantly advances understanding of microbial sulfur metabolism in the human gut, elucidating the complex interplay between diet, gut microbiota, and host sulfur metabolism. We highlight the microbial ASR pathway as an overlooked endogenous H2S producer and a potential therapeutic target for managing CD. Video Abstract.
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Affiliation(s)
- Wanrong Luo
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Er Road, Room 1209, Guangzhou, 510080, China
- Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Min Zhao
- Department of Gastroenterology, Shenzhen No.3 People's Hospital, Shenzhen, Guangdong, China
| | - Mohammed Dwidar
- Department of Cardiovascular & Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
- Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
| | - Yang Gao
- Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Liyuan Xiang
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Er Road, Room 1209, Guangzhou, 510080, China
| | - Xueting Wu
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Er Road, Room 1209, Guangzhou, 510080, China
| | - Marnix H Medema
- Bioinformatics Group, Wageningen University, Wageningen, The Netherlands
| | - Shu Xu
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Er Road, Room 1209, Guangzhou, 510080, China
| | - Xiaozhi Li
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Er Road, Room 1209, Guangzhou, 510080, China
| | - Hendrik Schäfer
- School of Life Sciences, University of Warwick, Coventry, UK
| | - Minhu Chen
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Er Road, Room 1209, Guangzhou, 510080, China.
| | - Rui Feng
- Department of Gastroenterology, the First Affiliated Hospital, Sun Yat-Sen University, No.58 Zhongshan Er Road, Room 1209, Guangzhou, 510080, China.
| | - Yijun Zhu
- Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China.
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González A, Odriozola I, Fullaondo A, Odriozola A. Microbiota and detrimental protein derived metabolites in colorectal cancer. ADVANCES IN GENETICS 2024; 112:255-308. [PMID: 39396838 DOI: 10.1016/bs.adgen.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Colorectal cancer (CRC) is the third leading cancer in incidence and the second leading cancer in mortality worldwide. There is growing scientific evidence to support the crucial role of the gut microbiota in the development of CRC. The gut microbiota is the complex community of microorganisms that inhabit the host gut in a symbiotic relationship. Diet plays a crucial role in modulating the risk of CRC, with a high intake of red and processed meat being a risk factor for the development of CRC. The production of metabolites derived from protein fermentation by the gut microbiota is considered a crucial element in the interaction between red and processed meat consumption and the development of CRC. This paper examines several metabolites derived from the bacterial fermentation of proteins associated with an increased risk of CRC. These metabolites include ammonia, polyamines, trimethylamine N-oxide (TMAO), N-nitroso compounds (NOC), hydrogen sulphide (H2S), phenolic compounds (p-cresol) and indole compounds (indolimines). These compounds are depicted and reviewed for their association with CRC risk, possible mechanisms promoting carcinogenesis and their relationship with the gut microbiota. Additionally, this paper analyses the evidence related to the role of red and processed meat intake and CRC risk and the factors and pathways involved in bacterial proteolytic fermentation in the large intestine.
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Affiliation(s)
- Adriana González
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain.
| | - Iñaki Odriozola
- Health Department of Basque Government, Donostia-San Sebastián, Spain
| | - Asier Fullaondo
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Adrian Odriozola
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
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Zhang X, Zhang X, Yang Y. Update of gut gas metabolism in ulcerative colitis. Expert Rev Gastroenterol Hepatol 2024; 18:339-349. [PMID: 39031456 DOI: 10.1080/17474124.2024.2383635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 07/19/2024] [Indexed: 07/22/2024]
Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease of the intestine. The intestinal microbiota is essential in the occurrence and development of UC. Gut gases are produced via bacterial fermentation or chemical interactions, which can reveal altered intestinal microbiota, abnormal cellular metabolism, and inflammation responses. Recent studies have demonstrated that UC patients have an altered gut gas metabolism. AREAS COVERED In this review, we integrate gut gas metabolism advances in UC and discuss intestinal gases' clinical values as new biomarkers or therapeutic targets for UC, providing the foundation for further research. Literature regarding gut gas metabolism and its significance in UC from inception to October 2023 was searched on the MEDLINE database and references from relevant articles were investigated. EXPERT OPINION Depending on their type, concentration, and volume, gut gases can induce or alleviate clinical symptoms and regulate intestinal motility, inflammatory responses, immune function, and oxidative stress, significantly impacting UC. Gut gases may function as new biomarkers and provide potential diagnostic or therapeutic targets for UC.
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Affiliation(s)
- Xiaohan Zhang
- Medical School, Nankai University, Tianjin, China
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xiuli Zhang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yunsheng Yang
- Microbiota Division, Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
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9
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Majumder A, Bano S. How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer. Biomolecules 2024; 14:633. [PMID: 38927037 PMCID: PMC11201633 DOI: 10.3390/biom14060633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 06/28/2024] Open
Abstract
Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks the colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists of almost 2000 different species of bacteria, forming a bioreactor fueled by dietary micronutrients to produce bioreactive compounds, which are absorbed by our body and signal to distant organs. Studies have shown that the Western diet, with fewer short-chain fatty acids (SCFAs), can alter the gut microbiome composition and cause the host's epigenetic reprogramming. Additionally, overproduction of H2S from the gut microbiome due to changes in diet patterns can further activate pro-inflammatory signaling pathways in UC. This review discusses how the Western diet affects the microbiome's function and alters the host's physiological homeostasis and susceptibility to UC. This article also covers the epidemiology, prognosis, pathophysiology, and current treatment strategies for UC, and how they are linked to colorectal cancer.
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Affiliation(s)
- Avisek Majumder
- Department of Medicine, University of California, San Francisco, CA 94158, USA
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10
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Cisek AA, Szymańska E, Aleksandrzak-Piekarczyk T, Cukrowska B. The Role of Methanogenic Archaea in Inflammatory Bowel Disease-A Review. J Pers Med 2024; 14:196. [PMID: 38392629 PMCID: PMC10890621 DOI: 10.3390/jpm14020196] [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: 12/31/2023] [Revised: 01/28/2024] [Accepted: 02/08/2024] [Indexed: 02/24/2024] Open
Abstract
Methanogenic archaea are a part of the commensal gut microbiota responsible for hydrogen sink and the efficient production of short-chain fatty acids. Dysbiosis of methanogens is suspected to play a role in pathogenesis of variety of diseases, including inflammatory bowel disease (IBD). Unlike bacteria, the diversity of archaea seems to be higher in IBD patients compared to healthy subjects, whereas the prevalence and abundance of gut methanogens declines in IBD, especially in ulcerative colitis. To date, studies focusing on methanogens in pediatric IBD are very limited; nevertheless, the preliminary results provide some evidence that methanogens may be influenced by the chronic inflammatory process in IBD. In this review, we demonstrated the development and diversity of the methanogenic community in IBD, both in adults and children.
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Affiliation(s)
- Agata Anna Cisek
- Department of Pathomorphology, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | - Edyta Szymańska
- Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
| | | | - Bożena Cukrowska
- Department of Pathomorphology, The Children's Memorial Health Institute, Av. Dzieci Polskich 20, 04-730 Warsaw, Poland
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11
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Hayes JA, Lunger AW, Sharma AS, Fernez MT, Carrier RL, Koppes AN, Koppes R, Woolston BM. Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on the host in a gut microphysiological system. Cell Rep 2023; 42:113481. [PMID: 37980564 PMCID: PMC10791167 DOI: 10.1016/j.celrep.2023.113481] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 10/05/2023] [Accepted: 11/06/2023] [Indexed: 11/21/2023] Open
Abstract
Hydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, with contradictory results stemming from experimental difficulties associated with accurate dosing and measuring H2S and the use of model systems that do not accurately represent the human gut environment. Here, we engineer Escherichia coli to titrate H2S across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip is engineered to maintain H2S gas tension and enables visualization of co-culture in real time with confocal microscopy. Engineered strains colonize the chip and are metabolically active for 2 days, during which they produce H2S across a 16-fold range and induce changes in host gene expression and metabolism in an H2S-concentration-dependent manner. These results validate a platform for studying the mechanisms underlying microbe-host interactions by enabling experiments that are infeasible with current animal and in vitro models.
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Affiliation(s)
- Justin A Hayes
- Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | - Anna W Lunger
- Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | - Aayushi S Sharma
- Department of Mechanical and Industrial Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Bioengineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | - Matthew T Fernez
- Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | - Rebecca L Carrier
- Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Bioengineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | - Abigail N Koppes
- Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Bioengineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | - Ryan Koppes
- Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
| | - Benjamin M Woolston
- Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
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12
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Wang M, Wang Z, Lessing DJ, Guo M, Chu W. Fusobacterium nucleatum and its metabolite hydrogen sulfide alter gut microbiota composition and autophagy process and promote colorectal cancer progression. Microbiol Spectr 2023; 11:e0229223. [PMID: 37889013 PMCID: PMC10714730 DOI: 10.1128/spectrum.02292-23] [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: 05/31/2023] [Accepted: 09/19/2023] [Indexed: 10/28/2023] Open
Abstract
IMPORTANCE Colorectal cancer (CRC) is the second most common cancer in the world; the main treatment for CRC is immunosuppressive therapy, but this therapy is only effective for a small percentage of CRC patients, so there is an urgent need for a treatment with fewer side effects and higher efficacy. This study demonstrated that Fusobacterium nucleatum with increased abundance in CRC can regulate the autophagy process and disrupt normal intestinal microbiota by producing hydrogen sulfide, factors that may be involved in the development and progression of CRC. This study may provide a reference for future CRC treatment options that are efficient and have fewer side effects.
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Affiliation(s)
- Minyu Wang
- Department of Pharmaceutical Microbiology, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Zheng Wang
- Department of Pharmaceutical Microbiology, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Duncan James Lessing
- Department of Pharmaceutical Microbiology, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Min Guo
- Department of Pharmaceutical Microbiology, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
| | - Weihua Chu
- Department of Pharmaceutical Microbiology, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
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13
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Luo Y, Chatre L, Melhem S, Al-Dahmani ZM, Homer NZM, Miedema A, Deelman LE, Groves MR, Feelisch M, Morton NM, Dolga A, van Goor H. Thiosulfate sulfurtransferase deficiency promotes oxidative distress and aberrant NRF2 function in the brain. Redox Biol 2023; 68:102965. [PMID: 38000344 PMCID: PMC10701433 DOI: 10.1016/j.redox.2023.102965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2023] [Revised: 11/06/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023] Open
Abstract
Thiosulfate sulfurtransferase (TST, EC 2.8.1.1) was discovered as an enzyme that detoxifies cyanide by conversion to thiocyanate (rhodanide) using thiosulfate as substrate; this rhodanese activity was subsequently identified to be almost exclusively located in mitochondria. More recently, the emphasis regarding its function has shifted to hydrogen sulfide metabolism, antioxidant defense, and mitochondrial function in the context of protective biological processes against oxidative distress. While TST has been described to play an important role in liver and colon, its function in the brain remains obscure. In the present study, we therefore sought to address its potential involvement in maintaining cerebral redox balance in a murine model of global TST deficiency (Tst-/- mice), primarily focusing on characterizing the biochemical phenotype of TST loss in relation to neuronal activity and sensitivity to oxidative stress under basal conditions. Here, we show that TST deficiency is associated with a perturbation of the reactive species interactome in the brain cortex secondary to altered ROS and RSS (specifically, polysulfide) generation as well as mitochondrial OXPHOS remodeling. These changes were accompanied by aberrant Nrf2-Keap1 expression and thiol-dependent antioxidant function. Upon challenging mice with the redox-active herbicide paraquat (25 mg/kg i.p. for 24 h), Tst-/- mice displayed a lower antioxidant capacity compared to wildtype controls (C57BL/6J mice). These results provide a first glimpse into the molecular and metabolic changes of TST deficiency in the brain and suggest that pathophysiological conditions associated with aberrant TST expression and/or activity renders neurons more susceptible to oxidative stress-related malfunction.
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Affiliation(s)
- Yang Luo
- University of Groningen, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, Groningen, the Netherlands; University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands
| | - Laurent Chatre
- Université de Caen Normandie, CNRS, Normandie University, ISTCT UMR6030, GIP Cyceron, F-14000 Caen, France
| | - Shaden Melhem
- Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
| | - Zayana M Al-Dahmani
- University of Groningen, Department of Pharmacy, Drug Design, Groningen, the Netherlands
| | - Natalie Z M Homer
- Mass Spectrometry Core, Edinburgh Clinical Research Facility, University of Edinburgh/BHF Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburghh, United Kingdom
| | - Anneke Miedema
- University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands
| | - Leo E Deelman
- University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands
| | - Matthew R Groves
- University of Groningen, Department of Pharmacy, Drug Design, Groningen, the Netherlands
| | - Martin Feelisch
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
| | - Nicholas M Morton
- Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom; Centre for Systems Health and Integrated Metabolic Research, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom
| | - Amalia Dolga
- University of Groningen, Department of Molecular Pharmacology, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, Groningen, the Netherlands
| | - Harry van Goor
- University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.
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14
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Fujiki Y, Tanaka T, Yakabe K, Seki N, Akiyama M, Uchida K, Kim YG. Hydrogen gas and the gut microbiota are potential biomarkers for the development of experimental colitis in mice. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2023; 5:e3. [PMID: 39290658 PMCID: PMC11406375 DOI: 10.1017/gmb.2023.17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 09/26/2023] [Accepted: 10/20/2023] [Indexed: 09/19/2024]
Abstract
Inflammatory bowel disease (IBD) is a chronic disease characterised by repeated relapses and remissions and a high recurrence rate even after symptom resolution. The primary method for IBD diagnosis is endoscopy; however, this method is expensive, invasive, and cumbersome to use serially. Therefore, more convenient and non-invasive methods for IBD diagnosis are needed. In this study, we aimed to identify biological gas markers for the development of gut inflammation. Using dextran sulphate sodium (DSS)-induced colitis mouse models, five biological gases were analysed to identify predictive markers for the development of gut inflammation. Additionally, the correlation between the changes in gas composition, gut microbiota, and inflammatory markers was assessed. The hydrogen (H2) level was found to be negatively correlated with the level of lipocalin-2 (LCN2), a gut inflammation biomarker, and weight loss due to DSS-induced colitis. Furthermore, gut microbes belonging to the Rikenellaceae and Akkermansiaceae families were positively correlated with LCN2 levels and weight loss, whereas Tannerellaceae abundance was negatively correlated with LCN2 level and weight loss and positively correlated with H2 levels. This study provides new insights for IBD diagnosis; the H2 levels in biological gases are a potential biomarker for intestinal inflammation, and specific gut microbes are associated with H2 level changes.
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Affiliation(s)
- Yuta Fujiki
- Research Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan
| | - Takahisa Tanaka
- Department of Materials Engineering, The University of Tokyo, Tokyo 113-8656, Japan
| | - Kyosuke Yakabe
- Research Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan
- Division of Biochemistry, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan
| | - Natsumi Seki
- Research Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan
| | - Masahiro Akiyama
- Research Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan
| | - Ken Uchida
- Department of Materials Engineering, The University of Tokyo, Tokyo 113-8656, Japan
| | - Yun-Gi Kim
- Research Center for Drug Discovery, Faculty of Pharmacy and Graduate School of Pharmaceutical Sciences, Keio University, Tokyo 105-8512, Japan
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15
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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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16
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Hayes JA, Lunger AW, Sharma AS, Fernez MT, Koppes AN, Koppes R, Woolston BM. Engineered bacteria titrate hydrogen sulfide and induce concentration-dependent effects on host in a gut microphysiological system. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.05.16.538950. [PMID: 37293009 PMCID: PMC10245736 DOI: 10.1101/2023.05.16.538950] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Hydrogen sulfide (H2S) is a gaseous microbial metabolite whose role in gut diseases is debated, largely due to the difficulty in controlling its concentration and the use of non-representative model systems in previous work. Here, we engineered E. coli to titrate H2S controllably across the physiological range in a gut microphysiological system (chip) supportive of the co-culture of microbes and host cells. The chip was designed to maintain H2S gas tension and enable visualization of co-culture in real-time with confocal microscopy. Engineered strains colonized the chip and were metabolically active for two days, during which they produced H2S across a sixteen-fold range and induced changes in host gene expression and metabolism in an H2S concentration-dependent manner. These results validate a novel platform for studying the mechanisms underlying microbe-host interactions, by enabling experiments that are infeasible with current animal and in vitro models.
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Affiliation(s)
- Justin A. Hayes
- Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA
| | - Anna W. Lunger
- Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA
| | - Aayushi S. Sharma
- Department of Mechanical and Industrial Engineering, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA
- Department of Bioengineering, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA
| | - Matthew T. Fernez
- Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA
| | - Abigail N. Koppes
- Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA
- Department of Bioengineering, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA
| | - Ryan Koppes
- Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA
| | - Benjamin M. Woolston
- Department of Chemical Engineering, Northeastern University, 360 Huntington Ave., Boston, MA 02115, USA
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17
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Aziz S, Waqas M, Iqbal A, Halim SA, Abdellattif MH, Khan A, Al-Harrasi A. Structure-based identification of potential substrate antagonists for isethionate sulfite-lyase enzyme of Bilophila Wadsworthia: Towards novel therapeutic intervention to curb gut-associated illness. Int J Biol Macromol 2023; 240:124428. [PMID: 37062383 DOI: 10.1016/j.ijbiomac.2023.124428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/03/2023] [Accepted: 04/09/2023] [Indexed: 04/18/2023]
Abstract
Bilophila wadsworthia is one of the prominent sources of hydrogen sulfide (H2S) production in appendices, excessive levels of which can result in a weaker colonic mucus barrier, inflammatory bowel disease, and colorectal cancer. Isethionate sulfite-lyase (IslA) enzyme catalyzes H2S production by cleaving CS bond in isethionate, producing acetaldehyde and sulfite. In this study, we aimed to identify potential substrate antagonists for IsIA using a structure-based drug design. Initially, pharmacophore-based computational screening of the ZINC20 database yielded 66 hits that were subjected to molecular docking targeting the isethionate binding site of IsIA. Based on striking docking scores, nine compounds showed strong interaction with critical IsIA residues (Arg189, Gln193, Glu470, Cys468, and Arg678), drug-like features, appropriate adsorption, metabolism, excretion, and excretion profile with non-toxicity. Molecular dynamics simulations uncovered the significant impact of binding the compounds on protein conformational dynamics. Finally, binding free energies revealed substantial binding affinity (ranging from -35.23 to -53.88 kcal/mol) of compounds (ZINC913876497, ZINC913856647, ZINC914263733, ZINC914137795, ZINC915757996, ZINC914357083, ZINC913934833, ZINC9143362047, and ZINC913854740) for IsIA. The compounds proposed herein through a multi-faceted computational strategy can be experimentally validated as potential substrate antagonists of B. wadsworthia's IsIA for developing new medications to curb gut-associated illness in the future.
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Affiliation(s)
- Shahkaar Aziz
- Institute of Biotechnology and Genetic Engineering, The University of Agriculture, Peshawar, Pakistan
| | - Muhammad Waqas
- Department of Biotechnology and Genetic Engineering, Hazara University, Mansehra, Pakistan; Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz, Nizwa, Oman
| | - Aqib Iqbal
- Institute of Biotechnology and Genetic Engineering, The University of Agriculture, Peshawar, Pakistan; Department of Biotechnology, Abdul Wali Khan University Mardan, Mardan, Pakistan.
| | - Sobia Ahsan Halim
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz, Nizwa, Oman
| | - Magda H Abdellattif
- Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
| | - Ajmal Khan
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz, Nizwa, Oman.
| | - Ahmed Al-Harrasi
- Natural and Medical Sciences Research Center, University of Nizwa, Birkat-ul-Mouz, Nizwa, Oman.
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18
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Yao CK, Sarbagili-Shabat C. Gaseous metabolites as therapeutic targets in ulcerative colitis. World J Gastroenterol 2023; 29:682-691. [PMID: 36742165 PMCID: PMC9896612 DOI: 10.3748/wjg.v29.i4.682] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 12/19/2022] [Accepted: 01/10/2023] [Indexed: 01/20/2023] Open
Abstract
Diet therapies are currently under-utilised in optimising clinical outcomes for patients with active ulcerative colitis (UC). Furthermore, existing dietary therapies are framed by poorly defined mechanistic targets to warrant its success. There is good evidence to suggest that microbial production of gaseous metabolites, hydrogen sulfide (H2S) and nitric oxide (NO) are implicated in the development of mucosal inflammation in UC. On a cellular level, exposure of the colonic epithelium to excessive concentrations of these gases are shown to promote functional defects described in UC. Hence, targeting bacterial production of these gases could provide an opportunity to formulate new dietary therapies in UC. Despite the paucity of evidence, there is epidemiological and clinical data to support the concept of reducing mucosal inflammation in UC via dietary strategies that reduce H2S. Several dietary components, namely sulphur-containing amino acids and inorganic sulphur have been shown to be influential in enhancing colonic H2S production. More recent data suggests increasing the supply of readily fermentable fibre as an effective strategy for H2S reduction. Conversely, very little is known regarding how diet alters microbial production of NO. Hence, the current evidence suggest that a whole diet approach is needed. Finally, biomarkers for assessing changes in microbial gaseous metabolites in response to dietary interventions are very much required. In conclusion, this review identifies a great need for high quality randomised-controlled trials to demonstrate the efficacy of a sulphide-reducing dietary therapy for patients with active UC.
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Affiliation(s)
- Chu K Yao
- Department of Gastroenterology, Monash University, Melbourne 3004, Australia
| | - Chen Sarbagili-Shabat
- Pediatric Gastroenterology Unit, PIBD Research Center, Wolfson Medical Center, Holon 5822012, Israel
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19
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Intestinal gas production by the gut microbiota: A review. J Funct Foods 2023. [DOI: 10.1016/j.jff.2022.105367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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20
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Methanogens and Hydrogen Sulfide Producing Bacteria Guide Distinct Gut Microbe Profiles and Irritable Bowel Syndrome Subtypes. Am J Gastroenterol 2022; 117:2055-2066. [PMID: 36114762 PMCID: PMC9722381 DOI: 10.14309/ajg.0000000000001997] [Citation(s) in RCA: 52] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 08/16/2022] [Indexed: 01/30/2023]
Abstract
INTRODUCTION Irritable bowel syndrome (IBS) includes diarrhea-predominant (IBS-D) and constipation-predominant (IBS-C) subtypes. We combined breath testing and stool microbiome sequencing to identify potential microbial drivers of IBS subtypes. METHODS IBS-C and IBS-D subjects from 2 randomized controlled trials (NCT03763175 and NCT04557215) were included. Baseline breath carbon dioxide, hydrogen (H 2 ), methane (CH 4 ), and hydrogen sulfide (H 2 S) levels were measured by gas chromatography, and baseline stool microbiome composition was analyzed by 16S rRNA sequencing. Microbial metabolic pathways were analyzed using Kyoto Encyclopedia of Genes and Genomes collection databases. RESULTS IBS-C subjects had higher breath CH 4 that correlated with higher gut microbial diversity and higher relative abundance (RA) of stool methanogens, predominantly Methanobrevibacter , as well as higher absolute abundance of Methanobrevibacter smithii in stool. IBS-D subjects had higher breath H 2 that correlated with lower microbial diversity and higher breath H 2 S that correlated with higher RA of H 2 S-producing bacteria, including Fusobacterium and Desulfovibrio spp. The predominant H 2 producers were different in these distinct microtypes, with higher RA of Ruminococcaceae and Christensenellaceae in IBS-C/CH 4 + (which correlated with Methanobacteriaceae RA) and higher Enterobacteriaceae RA in IBS-D. Finally, microbial metabolic pathway analysis revealed enrichment of Kyoto Encyclopedia of Genes and Genomes modules associated with methanogenesis and biosynthesis of methanogenesis cofactor F420 in IBS-C/CH 4 + subjects, whereas modules associated with H 2 S production, including sulfate reduction pathways, were enriched in IBS-D. DISCUSSION Our findings identify distinct gut microtypes linked to breath gas patterns in IBS-C and IBS-D subjects, driven by methanogens such as M. smithii and H 2 S producers such as Fusobacterium and Desulfovibrio spp, respectively.
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21
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Buonvino S, Arciero I, Melino S. Thiosulfate-Cyanide Sulfurtransferase a Mitochondrial Essential Enzyme: From Cell Metabolism to the Biotechnological Applications. Int J Mol Sci 2022; 23:ijms23158452. [PMID: 35955583 PMCID: PMC9369223 DOI: 10.3390/ijms23158452] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 07/27/2022] [Accepted: 07/27/2022] [Indexed: 11/16/2022] Open
Abstract
Thiosulfate: cyanide sulfurtransferase (TST), also named rhodanese, is an enzyme widely distributed in both prokaryotes and eukaryotes, where it plays a relevant role in mitochondrial function. TST enzyme is involved in several biochemical processes such as: cyanide detoxification, the transport of sulfur and selenium in biologically available forms, the restoration of iron–sulfur clusters, redox system maintenance and the mitochondrial import of 5S rRNA. Recently, the relevance of TST in metabolic diseases, such as diabetes, has been highlighted, opening the way for research on important aspects of sulfur metabolism in diabetes. This review underlines the structural and functional characteristics of TST, describing the physiological role and biomedical and biotechnological applications of this essential enzyme.
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A novel fluorescent probe for real-time imaging of thionitrous acid under inflammatory and oxidative conditions. Redox Biol 2022; 54:102372. [PMID: 35728302 PMCID: PMC9214870 DOI: 10.1016/j.redox.2022.102372] [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: 04/30/2022] [Revised: 06/07/2022] [Accepted: 06/13/2022] [Indexed: 11/17/2022] Open
Abstract
Thionitrous acid (HSNO), a crosstalk intermediate of two crucial gasotransmitters nitric oxide and hydrogen sulfide, plays a critical role in redox regulation of cellular signaling and functions. However, real-time and facile detection of HSNO with high selectivity and sensitivity remains highly challenging. Herein we report a novel fluorescent probe (SNP-1) for HSNO detection. SNP-1 has a simple molecular structure, but showing strong fluorescence, a low detection limit, a broad linear detection range (from nanomolar to micromolar concentrations), ultrasensitivity, and high selectivity for HSNO in both aqueous media and cells. Benefiting from these unique features, SNP-1 could effectively visualize changes of HSNO levels in mouse models of acute ulcerative colitis and renal ischemia/reperfusion injury. Moreover, the good correlation between colonic HSNO levels and disease activity index demonstrated that HSNO is a promising new diagnostic agent for acute ulcerative colitis. Therefore, SNP-1 can serve as a useful fluorescent probe for precision detection of HSNO in various biological systems, thereby facilitating mechanistic studies, therapeutic assessment, and high-content drug screening for corresponding diseases.
HSNO was the preferred intermediate to study crosstalk between H2S and NO. HSNO displayed translational potential for diagnosis and assessment of diseases. SNP-1 displayed excellent fluorescence performance for HSNO detection. SNP-1 could effectively image HSNO in cells and mouse models.
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Chen L, Gao Y, Zhao Y, Yang G, Wang C, Zhao Z, Li S. Chondroitin sulfate stimulates the secretion of H 2S by Desulfovibrio to improve insulin sensitivity in NAFLD mice. Int J Biol Macromol 2022; 213:631-638. [PMID: 35667460 DOI: 10.1016/j.ijbiomac.2022.05.195] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 05/12/2022] [Accepted: 05/30/2022] [Indexed: 01/21/2023]
Abstract
Hydrogen sulfide (H2S) is a bioactive gas regulating insulin secretion and sensitivity, produced by sulfate-reducing bacteria in the gut. The present study investigated the effect of chondroitin sulfate (CS) treatment, which indirectly increased the H2S production on nonalcoholic fatty liver disease (NAFLD). A 7-week CS supplementation had beneficial effects on body weight gain, liver function, hepatic histology, and serum lipid levels. CS could ameliorate diet-induced insulin resistance and improve insulin sensitivity via the AKT pathway, and modulate gut microbiota composition, especially increased the abundance of Desulfovibrio and elevated levels of hydrogen sulfide (H2S). Collectively, these findings suggested that CS treatment was positively correlated with Desulfovibrio in the gut, and the metabolic H2S flowed into the liver via the gut-liver axis, thereby triggering the AKT signaling pathway and improving insulin resistance. Thus, CS-induced alterations in the gut microbiota seem a promising for ameliorating NAFLD.
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Affiliation(s)
- Long Chen
- Institute of Animal Nutrition and Feed, Jilin Academy of Agricultural Sciences, Changchun 130033, PR China
| | - Yansong Gao
- Institute of Agricultural Products Processing Technology, Jilin Academy of Agricultural Sciences/National R&D Center for Milk Processing, Changchun 130033, PR China
| | - Yujuan Zhao
- Institute of Agricultural Products Processing Technology, Jilin Academy of Agricultural Sciences/National R&D Center for Milk Processing, Changchun 130033, PR China
| | - Ge Yang
- Institute of Agricultural Products Processing Technology, Jilin Academy of Agricultural Sciences/National R&D Center for Milk Processing, Changchun 130033, PR China
| | - Chao Wang
- Institute of Agricultural Products Processing Technology, Jilin Academy of Agricultural Sciences/National R&D Center for Milk Processing, Changchun 130033, PR China
| | - Zijian Zhao
- Institute of Agricultural Products Processing Technology, Jilin Academy of Agricultural Sciences/National R&D Center for Milk Processing, Changchun 130033, PR China.
| | - Shengyu Li
- Institute of Agricultural Products Processing Technology, Jilin Academy of Agricultural Sciences/National R&D Center for Milk Processing, Changchun 130033, PR China.
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Teigen L, Mathai PP, Lopez S, Matson M, Elkin B, Kozysa D, Kabage AJ, Hamilton M, Vaughn BP, Sadowsky MJ, Khoruts A. Differential hydrogen sulfide production by a human cohort in response to animal- and plant-based diet interventions. Clin Nutr 2022; 41:1153-1162. [PMID: 35500315 PMCID: PMC11082741 DOI: 10.1016/j.clnu.2022.03.028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 03/24/2022] [Accepted: 03/30/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hydrogen sulfide (H2S) is a toxic end-product of microbial fermentation produced in the colon that may play a role in the pathogenesis of several diseases, including ulcerative colitis and colon cancer. However, the effect of diet interventions on intestinal burden of H2S gas exposure remains poorly understood. OBJECTIVE Determine the effect of short-term (1-week) plant- and animal-based eating patterns on ex vivo fecal H2S production in healthy human volunteers. METHODS The study design was an open-label, cross-over diet study and diets were self-administered. Each participant consumed two interventional diets: 1) an animal-based, low fiber (i.e. western) diet and 2) a plant-based, high fiber diet, separated by a two-week washout period. Participants collected full stool samples at the end of each week, which were processed within 2 h of collection to capture H2S production. Microfluidic qPCR (MFQPCR) was used to simultaneously quantify multiple taxonomic and functional groups involved in sulfate reduction and the fecal microbiota was characterized through high-throughput DNA sequencing. RESULTS Median H2S production was higher following the animal-based diet compared to the plant-based diet (p = 0.02; median difference 29 ppm/g, 95% CI 16-97). However, there was substantial individual variability and 2 of 11 individuals (18%) produced more H2S on the plant-based diet. Using the top and bottom quartiles of H2S percent change between animal- and plant-based diet weeks to define responders and non-responders, significant taxonomic differences were observed between the responder and non-responder cohorts. CONCLUSIONS Here we report that substrate changes associated with a 1-week plant-based diet intervention resulted in lower ex vivo H2S production compared to a 1-week animal-based diet intervention in most healthy individuals. However, H2S responsiveness to diet was not uniform across the entire cohort, and potential H2S production enterotypes were characterized that may predict individualized H2S responsiveness to diet.
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Affiliation(s)
- Levi Teigen
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Prince P Mathai
- BioTechnology Institute, University of Minnesota, St. Paul, MN, USA
| | - Sharon Lopez
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Michael Matson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Baila Elkin
- Medical School, University of Minnesota, Minneapolis, MN, USA
| | - Daria Kozysa
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Amanda J Kabage
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Matthew Hamilton
- BioTechnology Institute, University of Minnesota, St. Paul, MN, USA
| | - Byron P Vaughn
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Michael J Sadowsky
- BioTechnology Institute, University of Minnesota, St. Paul, MN, USA; Department of Soil, Water, and Climate, USA; Department of Plant and Microbial Biology, USA
| | - Alexander Khoruts
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, MN, USA; BioTechnology Institute, University of Minnesota, St. Paul, MN, USA; Center for Immunology, University of Minnesota, Minneapolis, MN, USA.
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Burrichter AG, Dörr S, Bergmann P, Haiß S, Keller A, Fournier C, Franchini P, Isono E, Schleheck D. Bacterial microcompartments for isethionate desulfonation in the taurine-degrading human-gut bacterium Bilophila wadsworthia. BMC Microbiol 2021; 21:340. [PMID: 34903181 PMCID: PMC8667426 DOI: 10.1186/s12866-021-02386-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 11/08/2021] [Indexed: 11/15/2022] Open
Abstract
Background Bilophila wadsworthia, a strictly anaerobic, sulfite-reducing bacterium and common member of the human gut microbiota, has been associated with diseases such as appendicitis and colitis. It is specialized on organosulfonate respiration for energy conservation, i.e., utilization of dietary and host-derived organosulfonates, such as taurine (2-aminoethansulfonate), as sulfite donors for sulfite respiration, producing hydrogen sulfide (H2S), an important intestinal metabolite that may have beneficial as well as detrimental effects on the colonic environment. Its taurine desulfonation pathway involves the glycyl radical enzyme (GRE) isethionate sulfite-lyase (IslAB), which cleaves isethionate (2-hydroxyethanesulfonate) into acetaldehyde and sulfite. Results We demonstrate that taurine metabolism in B. wadsworthia 3.1.6 involves bacterial microcompartments (BMCs). First, we confirmed taurine-inducible production of BMCs by proteomic, transcriptomic and ultra-thin sectioning and electron-microscopical analyses. Then, we isolated BMCs from taurine-grown cells by density-gradient ultracentrifugation and analyzed their composition by proteomics as well as by enzyme assays, which suggested that the GRE IslAB and acetaldehyde dehydrogenase are located inside of the BMCs. Finally, we are discussing the recycling of cofactors in the IslAB-BMCs and a potential shuttling of electrons across the BMC shell by a potential iron-sulfur (FeS) cluster-containing shell protein identified by sequence analysis. Conclusions We characterized a novel subclass of BMCs and broadened the spectrum of reactions known to take place enclosed in BMCs, which is of biotechnological interest. We also provided more details on the energy metabolism of the opportunistic pathobiont B. wadsworthia and on microbial H2S production in the human gut. Supplementary Information The online version contains supplementary material available at 10.1186/s12866-021-02386-w.
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Affiliation(s)
- Anna G Burrichter
- Department of Biology, University of Konstanz, Konstanz, Germany. .,Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany. .,Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Faculty of Medicine, LMU Munich, Munich, Germany.
| | - Stefanie Dörr
- Department of Biology, University of Konstanz, Konstanz, Germany
| | - Paavo Bergmann
- Electron Microscopy Centre, Department of Biology, University of Konstanz, Konstanz, Germany
| | - Sebastian Haiß
- Department of Biology, University of Konstanz, Konstanz, Germany
| | - Anja Keller
- Department of Biology, University of Konstanz, Konstanz, Germany.,Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany
| | | | - Paolo Franchini
- Department of Biology, University of Konstanz, Konstanz, Germany
| | - Erika Isono
- Department of Biology, University of Konstanz, Konstanz, Germany
| | - David Schleheck
- Department of Biology, University of Konstanz, Konstanz, Germany. .,Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany.
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Braccia DJ, Jiang X, Pop M, Hall AB. The Capacity to Produce Hydrogen Sulfide (H 2S) via Cysteine Degradation Is Ubiquitous in the Human Gut Microbiome. Front Microbiol 2021; 12:705583. [PMID: 34745023 PMCID: PMC8564485 DOI: 10.3389/fmicb.2021.705583] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 09/29/2021] [Indexed: 01/09/2023] Open
Abstract
As one of the three mammalian gasotransmitters, hydrogen sulfide (H2S) plays a major role in maintaining physiological homeostasis. Endogenously produced H2S plays numerous beneficial roles including mediating vasodilation and conferring neuroprotection. Due to its high membrane permeability, exogenously produced H2S originating from the gut microbiota can also influence human physiology and is implicated in reducing intestinal mucosal integrity and potentiating genotoxicity and is therefore a potential target for therapeutic interventions. Gut microbial H2S production is often attributed to dissimilatory sulfate reducers such as Desulfovibrio and Bilophila species. However, an alternative source for H2S production, cysteine degradation, is present in some gut microbes, but the genes responsible for cysteine degradation have not been systematically annotated in all known gut microbes. We classify mechanisms of cysteine degradation into primary, secondary, and erroneous levels of H2S production and perform a comprehensive search for primary, secondary, and erroneous cysteine-degrading enzymes in 4,644 non-redundant bacterial genomes from the Unified Human Gastrointestinal Genome (UHGG) catalog. Of the 4,644 genomes we have putatively identified 2,046 primary, 1,951 secondary, and 5 erroneous cysteine-degrading species. We identified the presence of at least one putative cysteine-degrading bacteria in metagenomic data of 100% of 6,623 healthy subjects and the expression of cysteine-degrading genes in metatranscriptomic data of 100% of 736 samples taken from 318 individuals. Additionally, putative cysteine-degrading bacteria are more abundant than sulfate-reducing bacteria across healthy controls, IBD patients and CRC patients (p < 2.2e-16, Wilcoxon rank sum test). Although we have linked many taxa with the potential for cysteine degradation, experimental validation is required to establish the H2S production potential of the gut microbiome. Overall, this study improves our understanding of the capacity for H2S production by the human gut microbiome and may help to inform interventions to therapeutically modulate gut microbial H2S production.
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Affiliation(s)
- Domenick J Braccia
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, United States
| | - Xiaofang Jiang
- National Library of Medicine, National Institutes of Health, Bethesda, MD, United States
| | - Mihai Pop
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, United States.,Department of Computer Science, University of Maryland, College Park, College Park, MD, United States
| | - A Brantley Hall
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, United States.,Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, United States
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The Role of H 2S in the Gastrointestinal Tract and Microbiota. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1315:67-98. [PMID: 34302689 DOI: 10.1007/978-981-16-0991-6_4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The pathways and mechanisms of the production of H2S in the gastrointestinal tract are briefly described, including endogenous H2S produced by the organism and H2S from microorganisms in the gastrointestinal tract. In addition, the physiological regulatory functions of H2S on gastrointestinal motility, sensation, secretion and absorption, endocrine system, proliferation and differentiation of stem cells, and the possible mechanisms involved are introduced. In view of the complexity of biosynthesis, physiological roles, and the mechanism of H2S, this chapter focuses on the interactions and dynamic balance among H2S, gastrointestinal microorganisms, and the host. Finally, we focus on some clinical gastrointestinal diseases, such as inflammatory bowel disease, colorectal cancer, functional gastrointestinal disease, which might occur or develop when the above balance is broken. Pharmacological regulation of H2S or the intestinal microorganisms related to H2S might provide new therapeutic approaches for some gastrointestinal diseases.
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Myszkowska J, Derevenkov I, Makarov SV, Spiekerkoetter U, Hannibal L. Biosynthesis, Quantification and Genetic Diseases of the Smallest Signaling Thiol Metabolite: Hydrogen Sulfide. Antioxidants (Basel) 2021; 10:1065. [PMID: 34356298 PMCID: PMC8301176 DOI: 10.3390/antiox10071065] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 06/23/2021] [Accepted: 06/24/2021] [Indexed: 12/22/2022] Open
Abstract
Hydrogen sulfide (H2S) is a gasotransmitter and the smallest signaling thiol metabolite with important roles in human health. The turnover of H2S in humans is mainly governed by enzymes of sulfur amino acid metabolism and also by the microbiome. As is the case with other small signaling molecules, disease-promoting effects of H2S largely depend on its concentration and compartmentalization. Genetic defects that impair the biogenesis and catabolism of H2S have been described; however, a gap in knowledge remains concerning physiological steady-state concentrations of H2S and their direct clinical implications. The small size and considerable reactivity of H2S renders its quantification in biological samples an experimental challenge. A compilation of methods currently employed to quantify H2S in biological specimens is provided in this review. Substantial discrepancy exists in the concentrations of H2S determined by different techniques. Available methodologies permit end-point measurement of H2S concentration, yet no definitive protocol exists for the continuous, real-time measurement of H2S produced by its enzymatic sources. We present a summary of available animal models, monogenic diseases that impair H2S metabolism in humans including structure-function relationships of pathogenic mutations, and discuss possible approaches to overcome current limitations of study.
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Affiliation(s)
- Joanna Myszkowska
- Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;
| | - Ilia Derevenkov
- Department of Food Chemistry, Ivanovo State University of Chemistry and Technology, 153000 Ivanovo, Russia; (I.D.); (S.V.M.)
| | - Sergei V. Makarov
- Department of Food Chemistry, Ivanovo State University of Chemistry and Technology, 153000 Ivanovo, Russia; (I.D.); (S.V.M.)
| | - Ute Spiekerkoetter
- Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;
| | - Luciana Hannibal
- Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;
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Walker A, Schmitt-Kopplin P. The role of fecal sulfur metabolome in inflammatory bowel diseases. Int J Med Microbiol 2021; 311:151513. [PMID: 34147944 DOI: 10.1016/j.ijmm.2021.151513] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Revised: 04/22/2021] [Accepted: 05/17/2021] [Indexed: 12/17/2022] Open
Abstract
Sulfur metabolism and sulfur-containing metabolites play an important role in the human digestive system, and sulfur compounds and pathways are associated with inflammatory bowel diseases (IBD). In fact, cysteine metabolism results in the production of taurine and sulfate, and gut microbes catabolize them into hydrogen sulfide, a signaling molecule with various biological functions. Besides metabolites originating from sulfur metabolism, several other sulfur-containing metabolites of different classes were detected in human feces, consisting of non-volatile and volatile compounds. Sulfated steroids and bile acids such as taurine-conjugated bile acids are the major classes along with sulfur amino acids and sulfur-containing peptides. Indeed, sulfur-containing metabolites were described in stool samples from healthy subjects, patients suffering from colorectal cancer or IBD. In metabolomics-driven studies, around 50 known sulfur-containing metabolites were linked to IBD. Taurine, taurocholic acid, taurochenodeoxycholic acid, methionine, methanethiol and hydrogen sulfide were regularly reported in IBD studies, and most of them were elevated in stool samples from IBD patients. We summarized from this review that there is strong interplay between perturbed gut microbiota in IBD, and the consistently higher abundance of sulfur-containing metabolites, which potentially represent substrates for sulfidogenic bacteria such as Bilophila or Escherichia and promote their growth. These bacteria might shift their metabolism towards the degradation of taurine and cysteine and therefore to a higher hydrogen sulfide production.
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Affiliation(s)
- Alesia Walker
- Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, Neuherberg, Germany.
| | - Philippe Schmitt-Kopplin
- Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum München, Neuherberg, Germany; ZIEL Institute for Food and Health, Technical University of Munich, Freising, Germany; Chair of Analytical Food Chemistry, Technical University of Munich, Freising, Germany
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Yao CK, Burgell RE, Taylor KM, Ward MG, Friedman AB, Barrett JS, Muir JG, Gibson PR. Effects of fiber intake on intestinal pH, transit, and predicted oral mesalamine delivery in patients with ulcerative colitis. J Gastroenterol Hepatol 2021; 36:1580-1589. [PMID: 33091174 DOI: 10.1111/jgh.15311] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 09/15/2020] [Accepted: 10/13/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Limited data are available on the effects of fermentable fiber in altering intestinal pH and transit to predict efficacy-based delivery profiles of pH-dependent mesalamine coatings in ulcerative colitis (UC). This study aimed to examine regional pH and transit after acute changes in fermentable fiber intake in quiescent UC patients and their effects on drug release systems. METHODS In a randomized, double-blind study, 18 patients with quiescent UC and 10 healthy controls were supplied meals high (13 g) or low (≤ 2 g) in fermentable fiber and subsequently ingested a wireless pH-motility capsule. After a ≥ 3-day washout, they crossed over to the other diet. Measurements of intestinal pH and transit were used to predict drug release for the various pH-dependent coatings. RESULTS Increasing fermentable fiber intake lowered overall (median 6.2 [6.1-6.7] vs low: 6.9 [range or interquartile range: 6.4-7.4]; P = 0.01) and distal pH (7.8 [7.3-8.1] vs 8.2 [8.0-8.5]; P = 0.04) in controls. In UC patients, only cecal pH was decreased (high: 5.1 [4.8-5.5] vs low: 5.5 [5.3-5.7]; P < 0.01). Colonic transit in the UC cohort varied widely after a low-fiber intake but tended to normalize after the high fermentable fiber intake. Hypothetical coating dissolution profiles were heterogeneous in UC patients, with a multi-matrix delayed release system having the highest likelihood of patients (20-40%) with incomplete dissolution, and predominant small intestinal dissolution predicted for Eudragit L (94% patients) and S (44-69%). CONCLUSIONS Patients with quiescent UC have abnormalities in intestinal pH and transit in response to acute changes in fermentable fiber intake. These have potentially detrimental effects on predicted luminal release patterns of pH-dependent 5-aminosalicylic acid release systems.
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Affiliation(s)
- Chu K Yao
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Rebecca E Burgell
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Kirstin M Taylor
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Mark G Ward
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Antony B Friedman
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Jacqueline S Barrett
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Jane G Muir
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
| | - Peter R Gibson
- Department of Gastroenterology, Monash University and Alfred Hospital, Melbourne, Victoria, Australia
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Beneficial Effects of Natural Mineral Waters on Intestinal Inflammation and the Mucosa-Associated Microbiota. Int J Mol Sci 2021; 22:ijms22094336. [PMID: 33919372 PMCID: PMC8122343 DOI: 10.3390/ijms22094336] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/19/2021] [Accepted: 04/20/2021] [Indexed: 12/28/2022] Open
Abstract
Natural mineral water (NMWs) intake has been traditionally used in the treatment of various gastrointestinal diseases. We investigated the effect of two French NMWs, one a calcium and magnesium sulphate, sodium chloride, carbonic, and ferruginous water (NMW1), the other a mainly bicarbonate water (NMW2) on the prevention of intestinal inflammation. Intestinal epithelial cells stimulated with heat inactivated Escherichia coli or H2O2 were treated with NMWs to evaluate the anti-inflammatory effects. Moderate colitis was induced by 1% dextran sulfate sodium (DSS) in Balbc/J mice drinking NMW1, NWW2, or control water. General signs and histological features of colitis, fecal lipocalin-2 and pro-inflammatory KC cytokine levels, global mucosa-associated microbiota, were analyzed. We demonstrated that both NMW1 and NMW2 exhibited anti-inflammatory effects using intestinal cells. In induced-colitis mice, NMW1 was effective in dampening intestinal inflammation, with significant reductions in disease activity scores, fecal lipocalin-2 levels, pro-inflammatory KC cytokine release, and intestinal epithelial lesion sizes. Moreover, NMW1 was sufficient to prevent alterations in the mucosa-associated microbiota. These observations, through mechanisms involving modulation of the mucosa-associated microbiota, emphasize the need of investigation of the potential clinical efficiency of such NMWs to contribute, in human beings, to a state of low inflammation in inflammatory bowel disease.
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Environmental Impact of Sulfate-Reducing Bacteria, Their Role in Intestinal Bowel Diseases, and Possible Control by Bacteriophages. APPLIED SCIENCES-BASEL 2021. [DOI: 10.3390/app11020735] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Sulfate-reducing bacteria (SRB) represent a group of prokaryotic microorganisms that are widely spread in the anoxic environment (seabed, riverbed and lakebed sediments, mud, intestinal tract of humans and animals, metal surfaces). SRB species also have an impact on processes occurring in the intestinal tract of humans and animals, including the connections between their presence and inflammatory bowel disease (IBD). Since these SRB can develop antimicrobial resistance toward the drugs, including antibiotics and antimicrobial agents, bacteriophages could represent an additional potential effective treatment. The main objectives of the review were as follows: (a) to review SRB (both from intestinal and environmental sources) regarding their role in intestinal diseases as well as their influence in environmental processes; and (b) to review, according to literature data, the influence of bacteriophages on SRB and their possible applications. Since SRB can have a significant adverse influence on industry as well as on humans and animals health, phage treatment of SRB can be seen as a possible effective method of SRB inhibition. However, there are relatively few studies concerning the influence of phages on SRB strains. Siphoviridae and Myoviridae families represent the main sulfide-producing bacteria phages. The most recent studies induced, by UV light, bacteriophages from Desulfovibrio vulgaris NCIMB 8303 and Desulfovibrio desulfuricans ATCC 13541. Notwithstanding costly and medically significant negative impacts of phages on SRB, they have been the subject of relatively few studies. The current search for alternatives to chemical biocides and antibiotics has led to the renewed interest in phages as antibacterial biocontrol and therapeutic agents, including their use against SRB. Hence, phages might represent a promising treatment against SRB in the future.
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Blachier F, Andriamihaja M, Larraufie P, Ahn E, Lan A, Kim E. Production of hydrogen sulfide by the intestinal microbiota and epithelial cells and consequences for the colonic and rectal mucosa. Am J Physiol Gastrointest Liver Physiol 2021; 320:G125-G135. [PMID: 33084401 DOI: 10.1152/ajpgi.00261.2020] [Citation(s) in RCA: 70] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Among bacterial metabolites, hydrogen sulfide (H2S) has received increasing attention. The epithelial cells of the large intestine are exposed to two sources of H2S. The main one is the luminal source that results from specific bacteria metabolic activity toward sulfur-containing substrates. The other source in colonocytes is from the intracellular production mainly through cystathionine β-synthase (CBS) activity. H2S is oxidized by the mitochondrial sulfide oxidation unit, resulting in ATP synthesis, and, thus, establishing this compound as the first mineral energy substrate in colonocytes. However, when the intracellular H2S concentration exceeds the colonocyte capacity for its oxidation, it inhibits the mitochondrial respiratory chain, thus affecting energy metabolism. Higher luminal H2S concentration affects the integrity of the mucus layer and displays proinflammatory effects. However, a low/minimal amount of endogenous H2S exerts an anti-inflammatory effect on the colon mucosa, pointing out the ambivalent effect of H2S depending on its intracellular concentration. Regarding colorectal carcinogenesis, forced CBS expression in late adenoma-like colonocytes increased their proliferative activity, bioenergetics capacity, and tumorigenicity; whereas, genetic ablation of CBS in mice resulted in a reduced number of mutagen-induced aberrant crypt foci. Activation of endogenous H2S production and low H2S extracellular concentration enhance cancerous colorectal cell proliferation. Higher exogenous H2S concentrations markedly reduce mitochondrial ATP synthesis and proliferative capacity in cancerous cells and enhance glycolysis but do not affect their ATP cell content or viability. Thus, it appears that, notably through an effect on colonocyte energy metabolism, endogenous and microbiota-derived H2S are involved in the host intestinal physiology and physiopathology.
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Affiliation(s)
- François Blachier
- UMR PNCA, Nutrition Physiology and Alimentary Behavior, Université Paris-Saclay, AgroParisTech, INRAE, Paris, France
| | - Mireille Andriamihaja
- UMR PNCA, Nutrition Physiology and Alimentary Behavior, Université Paris-Saclay, AgroParisTech, INRAE, Paris, France
| | - Pierre Larraufie
- UMR PNCA, Nutrition Physiology and Alimentary Behavior, Université Paris-Saclay, AgroParisTech, INRAE, Paris, France
| | - Eunyeong Ahn
- Department of Food Science and Nutrition, Daegu Catholic University, Gyeongsan, South Korea
| | - Annaïg Lan
- UMR PNCA, Nutrition Physiology and Alimentary Behavior, Université Paris-Saclay, AgroParisTech, INRAE, Paris, France
| | - Eunjung Kim
- Department of Food Science and Nutrition, Daegu Catholic University, Gyeongsan, South Korea
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Chen YJ, Lee WH, Ho HJ, Tseng CH, Wu CY. An altered fecal microbial profiling in rosacea patients compared to matched controls. J Formos Med Assoc 2021; 120:256-264. [DOI: 10.1016/j.jfma.2020.04.034] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 02/13/2020] [Accepted: 04/29/2020] [Indexed: 02/08/2023] Open
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Wang X, Li J, Li N, Guan K, Yin D, Zhang H, Ding G, Hu Y. Evolution of Intestinal Gases and Fecal Short-Chain Fatty Acids Produced in vitro by Preterm Infant Gut Microbiota During the First 4 Weeks of Life. Front Pediatr 2021; 9:726193. [PMID: 34646797 PMCID: PMC8504453 DOI: 10.3389/fped.2021.726193] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 08/27/2021] [Indexed: 12/31/2022] Open
Abstract
Background: The production of intestinal gases and fecal short-chain fatty acids (SCFAs) by infant gut microbiota may have a significant impact on their health, but information about the composition and volume of intestinal gases and SCFA profiles in preterm infants is scarce. Objective: This study examined the change of the composition and volume of intestinal gases and SCFA profiles produced by preterm infant gut microbiota in vitro during the first 4 weeks of life. Methods: Fecal samples were obtained at five time points (within 3 days, 1 week, 2 weeks, 3 weeks, and 4 weeks) from 19 preterm infants hospitalized in the neonatal intensive care unit (NICU) of Shanghai Children's Hospital, Shanghai Jiao Tong University between May and July 2020. These samples were initially inoculated into four different media containing lactose (LAT), fructooligosaccharide (FOS), 2'-fucosyllactose (FL-2), and galactooligosaccharide (GOS) and thereafter fermented for 24 h under conditions mimicking those of the large intestine at 37.8°C under anaerobic conditions. The volume of total intestinal gases and the concentrations of individual carbon dioxide (CO2), hydrogen (H2), methane (CH4), and hydrogen sulfide (H2S) were measured by a gas analyzer. The concentrations of total SCFAs, individual acetic acid, propanoic acid, butyric acid, isobutyric acid, pentanoic acid, and valeric acid were measured by gas chromatography (GC). Results: The total volume of intestinal gases (ranging from 0.01 to 1.64 ml in medium with LAT; 0-1.42 ml with GOS; 0-0.91 ml with FOS; and 0-0.44 ml with FL-2) and the concentrations of CO2, H2, H2S, and all six fecal SCFAs increased with age (p-trends < 0.05). Among them, CO2 was usually the predominant intestinal gas, and acetic acid was usually the predominant SCFA. When stratified by birth weight (<1,500 and ≥1,500 g), gender, and delivery mode, the concentration of CO2 was more pronounced among infants whose weight was ≥1,500 g than among those whose weight was <1,500 g (p-trends < 0.05). Conclusions: Our findings suggested that the intestinal gases and SCFAs produced by preterm infant gut microbiota in vitro increased with age during the first 4 weeks of life.
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Affiliation(s)
- Xuefang Wang
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Juan Li
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Na Li
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Kunyu Guan
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Di Yin
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Huating Zhang
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Guodong Ding
- Department of Respiratory, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Yong Hu
- Department of Neonatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China
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Kushkevych I, Dordević D, Vítězová M. Possible synergy effect of hydrogen sulfide and acetate produced by sulfate-reducing bacteria on inflammatory bowel disease development. J Adv Res 2021; 27:71-78. [PMID: 33318867 PMCID: PMC7728581 DOI: 10.1016/j.jare.2020.03.007] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 03/19/2020] [Accepted: 03/22/2020] [Indexed: 11/20/2022] Open
Abstract
INTRODUCTION Increased numbers of sulfate-reducing bacteria (SRB) are often found in the feces of people and animals with inflammatory bowel disease. The final products of their metabolism are hydrogen sulfide and acetate, which are produced during dissimilatory sulfate reduction process. OBJECTIVES The aim of the study was to monitor processes concerning sulfate reduction microbial metabolisms, including: the main microbial genera monitoring and their hydrogen sulfide production in the intestines of healthy and not healthy individuals, phylogenetic analysis of SRB isolates, cluster analysis of SRB physiological and biochemical parameters, SRB growth kinetic parameters calculation, same as the application of the two-factor dispersion analysis for finding relationship between SRB biomass accumulation, temperature and pH. Feces samples from healthy people and patients with colitis were used for isolation of sulfate-reducing microbial communities. METHODS Microbiological, biochemical, biophysical, molecular biology methods, and statistical processing of the results have been used for making an evaluation of gained results. RESULTS Two dominant SRB morphotypes differed in colony size and quantitative ratio in the feces of healthy and colitis patients were observed and identified. In the feces of healthy people, 93% of SRB of morphotype I prevailed (Desulfovibrio) while morphotype II made only 7% (Desulfomicrobium); in the feces of patients with colitis, the ratio of these morphotypes was 99:1, respectively. Hydrogen sulfide concentrations are also higher in the feces of people with colitis and certain synergy effects exist among acetate produced by SRB. CONCLUSIONS The study results brought important findings concerning colony environments with developed colitis and these findings can lead to the development of possible risk indicators of ulcerative colitis prevalence.
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Affiliation(s)
- Ivan Kushkevych
- Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
- Department of Molecular Biology and Pharmaceutical Biotechnology, University of Veterinary and Pharmaceutical Sciences Brno, 61242 Brno, Czech Republic
| | - Dani Dordević
- Department of Plant Origin Foodstuffs Hygiene and Technology, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic
| | - Monika Vítězová
- Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 753/5, 625 00 Brno, Czech Republic
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Braccia DJ, Jiang X, Pop M, Hall AB. The Capacity to Produce Hydrogen Sulfide (H 2S) via Cysteine Degradation Is Ubiquitous in the Human Gut Microbiome. Front Microbiol 2021. [PMID: 34745023 DOI: 10.3389/fmicb.2021.705583/full] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/09/2023] Open
Abstract
As one of the three mammalian gasotransmitters, hydrogen sulfide (H2S) plays a major role in maintaining physiological homeostasis. Endogenously produced H2S plays numerous beneficial roles including mediating vasodilation and conferring neuroprotection. Due to its high membrane permeability, exogenously produced H2S originating from the gut microbiota can also influence human physiology and is implicated in reducing intestinal mucosal integrity and potentiating genotoxicity and is therefore a potential target for therapeutic interventions. Gut microbial H2S production is often attributed to dissimilatory sulfate reducers such as Desulfovibrio and Bilophila species. However, an alternative source for H2S production, cysteine degradation, is present in some gut microbes, but the genes responsible for cysteine degradation have not been systematically annotated in all known gut microbes. We classify mechanisms of cysteine degradation into primary, secondary, and erroneous levels of H2S production and perform a comprehensive search for primary, secondary, and erroneous cysteine-degrading enzymes in 4,644 non-redundant bacterial genomes from the Unified Human Gastrointestinal Genome (UHGG) catalog. Of the 4,644 genomes we have putatively identified 2,046 primary, 1,951 secondary, and 5 erroneous cysteine-degrading species. We identified the presence of at least one putative cysteine-degrading bacteria in metagenomic data of 100% of 6,623 healthy subjects and the expression of cysteine-degrading genes in metatranscriptomic data of 100% of 736 samples taken from 318 individuals. Additionally, putative cysteine-degrading bacteria are more abundant than sulfate-reducing bacteria across healthy controls, IBD patients and CRC patients (p < 2.2e-16, Wilcoxon rank sum test). Although we have linked many taxa with the potential for cysteine degradation, experimental validation is required to establish the H2S production potential of the gut microbiome. Overall, this study improves our understanding of the capacity for H2S production by the human gut microbiome and may help to inform interventions to therapeutically modulate gut microbial H2S production.
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Affiliation(s)
- Domenick J Braccia
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, United States
| | - Xiaofang Jiang
- National Library of Medicine, National Institutes of Health, Bethesda, MD, United States
| | - Mihai Pop
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, United States
- Department of Computer Science, University of Maryland, College Park, College Park, MD, United States
| | - A Brantley Hall
- Center for Bioinformatics and Computational Biology, University of Maryland, College Park, College Park, MD, United States
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, United States
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Manandhar S, Sinha P, Ejiwale G, Bhatia M. Hydrogen Sulfide and its Interaction with Other Players in Inflammation. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1315:129-159. [PMID: 34302691 DOI: 10.1007/978-981-16-0991-6_6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hydrogen sulfide (H2S) plays a vital role in human physiology and in the pathophysiology of several diseases. In addition, a substantial role of H2S in inflammation has emerged. This chapter will discuss the involvement of H2S in various inflammatory diseases. Furthermore, the contribution of reactive oxygen species (ROS), adhesion molecules, and leukocyte recruitment in H2S-mediated inflammation will be discussed. The interrelationship of H2S with other gasotransmitters in inflammation will also be examined. There is mixed literature on the contribution of H2S to inflammation due to studies reporting both pro- and anti-inflammatory actions. These apparent discrepancies in the literature could be resolved with further studies.
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Affiliation(s)
- Sumeet Manandhar
- Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand
| | - Priyanka Sinha
- Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand
| | - Grace Ejiwale
- Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand
| | - Madhav Bhatia
- Department of Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
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Association of colitis with gut-microbiota dysbiosis in clathrin adapter AP-1B knockout mice. PLoS One 2020; 15:e0228358. [PMID: 32208434 PMCID: PMC7093000 DOI: 10.1371/journal.pone.0228358] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 01/13/2020] [Indexed: 12/21/2022] Open
Abstract
Inflammatory bowel disease results from alterations in the immune system and intestinal microbiota. The role of intestinal epithelial cells (IECs) in maintaining gut homeostasis is well known and its perturbation often causes gastrointestinal disorders including IBD. The epithelial specific adaptor protein (AP)-1B is involved in the establishment of the polarity of IECs. Deficiency of the AP-1B μ subunit (Ap1m2-/-) leads to the development of chronic colitis in mice. However, how this deficiency affects the gut microbes and its potential functions remains elusive. To gain insights into the gut microbiome of Ap1m2-/- mice having the colitis phenotype, we undertook shotgun metagenomic sequencing analysis of knockout mice. We found important links to the microbial features involved in altering various physiological pathways, including carbohydrate metabolism, nutrient transportation, oxidative stress, and bacterial pathogenesis (cell motility). In addition, an increased abundance of sulfur-reducing and lactate-producing bacteria has been observed which may aggravate the colitis condition.
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40
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Bannaga AS, Farrugia A, Arasaradnam RP. Diagnosing Inflammatory bowel disease using noninvasive applications of volatile organic compounds: a systematic review. Expert Rev Gastroenterol Hepatol 2019; 13:1113-1122. [PMID: 31657950 DOI: 10.1080/17474124.2019.1685873] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction: Inflammatory bowel disease (IBD) is a common disease with significant morbidity. Noninvasive diagnostic techniques are lacking in IBD. Currently, fecal calprotectin is a sensitive marker of gut inflammation however is not specific to Crohn's disease (CD) or ulcerative colitis (UC) alone. Volatile organic compounds (VOCs) were shown to have potential in IBD diagnosis.Areas covered: This systematic review aimed to examine the next-generation diagnosis of IBD in adults and children using VOCs. An in-depth literature-based search of current clinical studies of VOCs in the diagnosis of IBD was undertaken. Accuracy of IBD detection varied according to the technologies applied. Breath VOCs studies were pooled giving an overall sensitivity of 85% (95%CI: 79-89%) and specificity of 79% (95%CI 73-84%) whilst pooled fecal VOCs studies revealed a sensitivity of 87% (95%CI 77-93%) and specificity of 91% (95%CI 82-96%). Studies were limited by the variance of techniques applied in VOCs detection and the absence of well-designed longitudinal studies.Expert opinion: VOCs can be consistently and effectively detected in urine, breath, and stool in IBD patients. The sensitivity of breath VOCs in detecting IBD was comparable to feces. However, optimal VOCs detection methodology and biological sampling still need to be standardized..
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Affiliation(s)
- Ayman S Bannaga
- University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK.,Warwick Medical School, University of Warwick, Coventry, UK
| | - Alexia Farrugia
- University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK.,Warwick Medical School, University of Warwick, Coventry, UK
| | - Ramesh P Arasaradnam
- University Hospital Coventry and Warwickshire NHS Trust, Coventry, UK.,Warwick Medical School, University of Warwick, Coventry, UK.,Faculty of Health Science, University of Coventry, Coventry, UK.,Division of Health Sciences, University of Leicester, Leicester, UK
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Hydrogen sulfide donor GYY4137 suppresses proliferation of human colorectal cancer Caco-2 cells by inducing both cell cycle arrest and cell death. Heliyon 2019; 5:e02244. [PMID: 31440595 PMCID: PMC6699460 DOI: 10.1016/j.heliyon.2019.e02244] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 06/24/2019] [Accepted: 08/02/2019] [Indexed: 01/01/2023] Open
Abstract
Conflicting data regarding the ability of hydrogen sulfide (H2S), which reaches high levels in the large intestine owing to biosynthesis in the intestinal cells and intestinal bacteria, to promote or inhibit colorectal cancer cell proliferation have been reported recently. In the present study, the effect of H2S on the proliferation of the human colorectal cancer cell line Caco-2 was examined by using the H2S donor GYY4137. At concentrations of 0.5 mM and 1.0 mM, GYY4137 significantly inhibited Caco-2 cell viability. Cell cycle analysis, and apoptosis and necrosis detection revealed that the anti-proliferative effect of GYY4137 was partially attributable to the induction of S-G2/M cell cycle arrest, apoptosis and necrosis. These results suggest that H2S has the potential to suppress human colorectal cancer cell proliferation by influencing both cell cycle and cell death.
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42
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Study of in vitro digestion of Tenebrio molitor flour for evaluation of its impact on the human gut microbiota. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.05.024] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Kastl AJ, Terry NA, Wu GD, Albenberg LG. The Structure and Function of the Human Small Intestinal Microbiota: Current Understanding and Future Directions. Cell Mol Gastroenterol Hepatol 2019; 9:33-45. [PMID: 31344510 PMCID: PMC6881639 DOI: 10.1016/j.jcmgh.2019.07.006] [Citation(s) in RCA: 200] [Impact Index Per Article: 33.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 07/17/2019] [Accepted: 07/17/2019] [Indexed: 02/07/2023]
Abstract
Despite growing literature characterizing the fecal microbiome and its association with health and disease, few studies have analyzed the microbiome of the small intestine. Here, we examine what is known about the human small intestinal microbiota in terms of community structure and functional properties. We examine temporal dynamics of select bacterial populations in the small intestine, and the effects of dietary carbohydrates and fats on shaping these populations. We then evaluate dysbiosis in the small intestine in several human disease models, including small intestinal bacterial overgrowth, short-bowel syndrome, pouchitis, environmental enteric dysfunction, and irritable bowel syndrome. What is clear is that the bacterial biology, and mechanisms of bacteria-induced pathophysiology, are enormously broad and elegant in the small intestine. Studying the small intestinal microbiota is challenged by rapidly fluctuating environmental conditions in these intestinal segments, as well as the complexity of sample collection and bioinformatic analysis. Because the functionality of the digestive tract is determined primarily by the small intestine, efforts must be made to better characterize this unique and important microbial ecosystem.
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Affiliation(s)
- Arthur J. Kastl
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania,Correspondence Address correspondence to: Arthur J. Kastl Jr, MD, Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, 3401 Civic Center Boulevard, 7NW, Philadelphia, Pennsylvania 19104. fax: (215) 590-3606.
| | - Natalie A. Terry
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Gary D Wu
- Division of Gastroenterology, Hepatology, and Nutrition, The University of Pennsylvania, Philadelphia, Pennsylvania
| | - Lindsey G. Albenberg
- Division of Gastroenterology, Hepatology, and Nutrition, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
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Castro F, de Souza HSP. Dietary Composition and Effects in Inflammatory Bowel Disease. Nutrients 2019; 11:1398. [PMID: 31234325 PMCID: PMC6628370 DOI: 10.3390/nu11061398] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 06/14/2019] [Accepted: 06/19/2019] [Indexed: 02/07/2023] Open
Abstract
Dramatic changes in the environment and human lifestyle have been associated with the rise of various chronic complex diseases, such as inflammatory bowel disease (IBD). A dysbiotic gut microbiota has been proposed as a crucial pathogenic element, contributing to immune imbalances and fostering a proinflammatory milieu, which may be associated with disease relapses or even the initiation of IBD. In addition to representing important regulators of the mucosal immunity and the composition of the gut microbiota, food components have been shown to be potential environmental triggers of epigenetic modifications. In the context of chronic intestinal inflammation, dietary habits and specific food components have been implicated as important modulators of epigenetic mechanisms, including DNA methylation, which may predispose a person to the increased risk of the initiation and evolution of IBD. This review provides novel insights about how dietary factors may interact with the intestinal mucosa and modulate immune homeostasis by shaping the intestinal ecosystem, as well as the potential influence of diet in the etiopathogenesis and management of IBD.
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Affiliation(s)
- Fernando Castro
- Department of Internal Medicine, School of Medicine, Federal University of Rio de Janeiro, 21941-913 Rio de Janeiro, Brazil.
| | - Heitor S P de Souza
- Department of Internal Medicine, School of Medicine, Federal University of Rio de Janeiro, 21941-913 Rio de Janeiro, Brazil.
- Department of Internal Medicine, D'Or Institute for Research and Education (IDOR), 22281-100 Rio de Janeiro, Brazil.
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Dietary Factors in Sulfur Metabolism and Pathogenesis of Ulcerative Colitis. Nutrients 2019; 11:nu11040931. [PMID: 31027194 PMCID: PMC6521024 DOI: 10.3390/nu11040931] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2019] [Revised: 04/20/2019] [Accepted: 04/23/2019] [Indexed: 02/07/2023] Open
Abstract
The biogeography of inflammation in ulcerative colitis (UC) suggests a proximal to distal concentration gradient of a toxin. Hydrogen sulfide (H2S) has long been considered one such toxin candidate, and dietary sulfur along with the abundance of sulfate reducing bacteria (SRB) were considered the primary determinants of H2S production and clinical course of UC. The metabolic milieu in the lumen of the colon, however, is the result of a multitude of factors beyond dietary sulfur intake and SRB abundance. Here we present an updated formulation of the H2S toxin hypothesis for UC pathogenesis, which strives to incorporate the interdependency of diet composition and the metabolic activity of the entire colon microbial community. Specifically, we suggest that the increasing severity of inflammation along the proximal-to-distal axis in UC is due to the dilution of beneficial factors, concentration of toxic factors, and changing detoxification capacity of the host, all of which are intimately linked to the nutrient flow from the diet.
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Abstract
Covering: up to the end of 2017 The human body is composed of an equal number of human and microbial cells. While the microbial community inhabiting the human gastrointestinal tract plays an essential role in host health, these organisms have also been connected to various diseases. Yet, the gut microbial functions that modulate host biology are not well established. In this review, we describe metabolic functions of the human gut microbiota that involve metalloenzymes. These activities enable gut microbial colonization, mediate interactions with the host, and impact human health and disease. We highlight cases in which enzyme characterization has advanced our understanding of the gut microbiota and examples that illustrate the diverse ways in which metalloenzymes facilitate both essential and unique functions of this community. Finally, we analyze Human Microbiome Project sequencing datasets to assess the distribution of a prominent family of metalloenzymes in human-associated microbial communities, guiding future enzyme characterization efforts.
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Saksrithai K, King A. Lactobacillus and dietary sunflower meal supplementation in layer diets: Effects on specific serum content and hydrogen sulfide concentration in layer manure. Res Vet Sci 2019; 122:64-71. [DOI: 10.1016/j.rvsc.2018.11.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 11/11/2018] [Indexed: 11/29/2022]
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Figliuolo VR, Coutinho-Silva R, Coutinho CMLM. Contribution of sulfate-reducing bacteria to homeostasis disruption during intestinal inflammation. Life Sci 2018; 215:145-151. [PMID: 30414430 DOI: 10.1016/j.lfs.2018.11.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 11/02/2018] [Accepted: 11/05/2018] [Indexed: 12/26/2022]
Abstract
Alteration in microbial populations and metabolism are key events associated with disruption of intestinal homeostasis and immune tolerance during intestinal inflammation. A substantial imbalance in bacterial populations in the intestine and their relationships with the host have been observed in patients with inflammatory bowel disease (IBD), believed to be part of an intricate mechanism of triggering and progression of intestinal inflammation. Because elevated numbers of sulfate-reducing bacteria (SRB) have been found in the intestines of patients with IBD, the study of their interaction with intestinal cells and their potential involvement in IBD has been the focus of investigation to better understand the intestinal pathology during IBD, as well as to find new ways to treat the disease. SRB not only directly interact with intestinal epithelial cells during intestinal inflammation but may also promote intestinal damage through generation of hydrogen sulfide at high levels. Herein we review the literature to discuss the various aspects of SRB interaction with host intestinal tissue, focusing on their interaction with intestinal epithelial and immune cells during intestinal inflammation.
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Affiliation(s)
- Vanessa Ribeiro Figliuolo
- Instituto de Biofísica Carlos Chagas Filho - IBCCF, Universidade Federal do Rio de Janeiro, RJ, Brazil; LITEB, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil; Department of Pediatrics, University of Arizona, Tucson, AZ, USA
| | - Robson Coutinho-Silva
- Instituto de Biofísica Carlos Chagas Filho - IBCCF, Universidade Federal do Rio de Janeiro, RJ, Brazil
| | - Claudia Mara Lara Melo Coutinho
- Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niteroi, RJ, Brazil; LITEB, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brazil.
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Yao CK, Rotbart A, Ou JZ, Kalantar-Zadeh K, Muir JG, Gibson PR. Modulation of colonic hydrogen sulfide production by diet and mesalazine utilizing a novel gas-profiling technology. Gut Microbes 2018; 9:510-522. [PMID: 29561196 PMCID: PMC6287689 DOI: 10.1080/19490976.2018.1451280] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 02/28/2018] [Accepted: 03/05/2018] [Indexed: 02/06/2023] Open
Abstract
Excessive hydrogen sulfide (H2S) production from gut microbial metabolism may have clinically important relevance in the pathogenesis of gut disorders, including ulcerative colitis. However, little is known regarding factors that alter its production. Using a newly-designed in vitro gas-profiling technology, the study aimed to verify real-time H2S measurement reproducibility and thereafter, assess its production following exposure to dietary factors and 5-aminosalicylate acid (5-ASA). Measurements of H2S, carbon dioxide, hydrogen and methane measurements were compared between gas-profiling systems. Homogenized slurries were prepared from freshly-passed healthy human feces. Fifty ml slurries were aliquoted into separate fermentation chambers and substrates added including 1 g highly fermentable fructo-oligosaccharides (FOS) or resistant starch Hi-Maize (RS), or minimally fermentable psyllium or sterculia, 1 g cysteine, 0.9 g sodium sulfate or 1.2 mL of 1 M 5-ASA alone or in combinations. H2S release was sampled every 5 mins over 4-h and expressed relative to unspiked controls. RS suppressed H2S production by a mean 89.0 (SEM 4.8)% and FOS by 82.2 (6.2)% compared to <35 (17)% by psyllium and sterculia (p<0.001, two-way ANOVA). Cysteine stimulated H2S production by 1557 (532)%. The addition of FOS to slurries containing cysteine significantly suppressed H2S by 90 (2)% over the addition of 5-ASA (0.3 (2)%, p<0.001). Sulfate and 5-ASA had minimal overall effects. In conclusion, the H2S-profiling technology is a reproducible tool. Production of H2S is greatly enhanced by sulfur-amino acids but not inorganic sulfate, and is effectively suppressed by readily fermentable fibers. These findings inform potential designs of dietary therapies to reduce H2S production in vivo.
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Affiliation(s)
- Chu K. Yao
- Department of Gastroenterology, Central Clinical School, Alfred Centre, Monash University & Alfred Health, Melbourne, Australia
| | - Asaf Rotbart
- School of Engineering, RMIT University, Melbourne, Australia
| | - Jian Z. Ou
- School of Engineering, RMIT University, Melbourne, Australia
| | | | - Jane G. Muir
- Department of Gastroenterology, Central Clinical School, Alfred Centre, Monash University & Alfred Health, Melbourne, Australia
| | - Peter R. Gibson
- Department of Gastroenterology, Central Clinical School, Alfred Centre, Monash University & Alfred Health, Melbourne, Australia
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Ong HS, Yim HCH. Microbial Factors in Inflammatory Diseases and Cancers. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1024:153-174. [PMID: 28921469 DOI: 10.1007/978-981-10-5987-2_7] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
The intestinal microbes form a symbiotic relationship with their human host to harvest energy for themselves and their host and to shape the immune system of their host. However, alteration of this relationship, which is named as a dysbiosis, has been associated with the development of different inflammatory diseases and cancers. It is found that metabolites, cellular components, and virulence factors derived from the gut microbiota interact with the host locally or systemically to modulate the dysbiosis and the development of these diseases. In this book chapter, we discuss the role of these microbial factors in regulating the host signaling pathways, the composition and load of the gut microbiota, the co-metabolism of the host and the microbiota, the host immune system, and physiology. In particular, we highlight how each microbial factor can contribute in the manifestation of many diseases such as cancers, Inflammatory Bowel Diseases, obesity, type-2 diabetes, non-alcoholic fatty liver diseases, nonalcoholic steatohepatitis, and cardiovascular diseases.
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Affiliation(s)
- Hong Sheng Ong
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Acton, Canberra, 2601, ACT, Australia
| | - Howard Chi Ho Yim
- Department of Medicine, St George & Sutherland Clinical School, Faculty of Medicine, University of New South Wales, Australia, Level 2 Clinical Sciences (WR Pitney) Building, St George Hospital, Short St, Kogarah, NSW, 2217, Australia.
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