{"title":"Role of bacteriophages in shaping gut microbial community.","authors":"Md Rayhan Mahmud, Sanjida Khanam Tamanna, Sharmin Akter, Lincon Mazumder, Sumona Akter, Md Rakibul Hasan, Mrityunjoy Acharjee, Israt Zahan Esti, Md Saidul Islam, Md Maksudur Rahman Shihab, Md Nahian, Rubaiya Gulshan, Sadia Naser, Anna Maria Pirttilä","doi":"10.1080/19490976.2024.2390720","DOIUrl":"10.1080/19490976.2024.2390720","url":null,"abstract":"<p><p>Phages are the most diversified and dominant members of the gut virobiota. They play a crucial role in shaping the structure and function of the gut microbial community and consequently the health of humans and animals. Phages are found mainly in the mucus, from where they can translocate to the intestinal organs and act as a modulator of gut microbiota. Understanding the vital role of phages in regulating the composition of intestinal microbiota and influencing human and animal health is an emerging area of research. The relevance of phages in the gut ecosystem is supported by substantial evidence, but the importance of phages in shaping the gut microbiota remains unclear. Although information regarding general phage ecology and development has accumulated, detailed knowledge on phage-gut microbe and phage-human interactions is lacking, and the information on the effects of phage therapy in humans remains ambiguous. In this review, we systematically assess the existing data on the structure and ecology of phages in the human and animal gut environments, their development, possible interaction, and subsequent impact on the gut ecosystem dynamics. We discuss the potential mechanisms of prophage activation and the subsequent modulation of gut bacteria. We also review the link between phages and the immune system to collect evidence on the effect of phages on shaping the gut microbial composition. Our review will improve understanding on the influence of phages in regulating the gut microbiota and the immune system and facilitate the development of phage-based therapies for maintaining a healthy and balanced gut microbiota.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2390720"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-01-01Epub Date: 2024-08-21DOI: 10.1080/19490976.2024.2391505
Femke M Prins, Iwan J Hidding, Marjolein A Y Klaassen, Valerie Collij, Johannes P D Schultheiss, Werna T C Uniken Venema, Amber Bangma, Jurne B Aardema, Bernadien H Jansen, Wout G N Mares, Ben J M Witteman, Eleonora A M Festen, Gerard Dijkstra, Marijn C Visschedijk, Herma H Fidder, Arnau Vich Vila, Bas Oldenburg, Ranko Gacesa, Rinse K Weersma
{"title":"Limited predictive value of the gut microbiome and metabolome for response to biological therapy in inflammatory bowel disease.","authors":"Femke M Prins, Iwan J Hidding, Marjolein A Y Klaassen, Valerie Collij, Johannes P D Schultheiss, Werna T C Uniken Venema, Amber Bangma, Jurne B Aardema, Bernadien H Jansen, Wout G N Mares, Ben J M Witteman, Eleonora A M Festen, Gerard Dijkstra, Marijn C Visschedijk, Herma H Fidder, Arnau Vich Vila, Bas Oldenburg, Ranko Gacesa, Rinse K Weersma","doi":"10.1080/19490976.2024.2391505","DOIUrl":"10.1080/19490976.2024.2391505","url":null,"abstract":"<p><p>Emerging evidence suggests the gut microbiome's potential in predicting response to biologic treatments in patients with inflammatory bowel disease (IBD). In this prospective study, we aimed to predict treatment response to vedolizumab and ustekinumab, integrating clinical data, gut microbiome profiles based on metagenomic sequencing, and untargeted fecal metabolomics. We aimed to identify predictive biomarkers and attempted to replicate microbiome-based signals from previous studies. We found that the predictive utility of the gut microbiome and fecal metabolites for treatment response was marginal compared to clinical features alone. Testing our identified microbial ratios in an external cohort reinforced the lack of predictive power of the microbiome. Additionally, we could not confirm previously published predictive signals observed in similar sized cohorts. Overall, these findings highlight the importance of external validation and larger sample sizes, to better understand the microbiome's impact on therapy outcomes in the setting of biologicals in IBD before potential clinical implementation.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2391505"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-01-01Epub Date: 2024-08-27DOI: 10.1080/19490976.2024.2392877
Kaitlyn Grando, Shingo Bessho, Kayla Harrell, Kathrine Kyrylchuk, Alejandro M Pantoja, Sophia Olubajo, Francisco J Albicoro, Andres Klein-Szanto, Çagla Tükel
{"title":"Bacterial amyloid curli activates the host unfolded protein response via IRE1α in the presence of HLA-B27.","authors":"Kaitlyn Grando, Shingo Bessho, Kayla Harrell, Kathrine Kyrylchuk, Alejandro M Pantoja, Sophia Olubajo, Francisco J Albicoro, Andres Klein-Szanto, Çagla Tükel","doi":"10.1080/19490976.2024.2392877","DOIUrl":"10.1080/19490976.2024.2392877","url":null,"abstract":"<p><p><i>Salmonella enterica</i> serovar Typhimurium (STm) causes gastroenteritis and can progress to reactive arthritis (ReA). STm forms biofilms in the gut that secrete the amyloid curli, which we previously demonstrated can trigger autoimmunity in mice. HLA-B27 is a genetic risk factor for ReA; activation of the unfolded protein response (UPR) due to HLA-B27 misfolding is thought to play a critical role in ReA pathogenesis. To determine whether curli exacerbates HLA-B27-induced UPR, bone marrow-derived macrophages (BMDMs) isolated from HLA-B27 transgenic (tg) mice were used. BMDMs treated with purified curli exhibited elevated UPR compared to C57BL/6, and curli-induced IL-6 was reduced by pre-treating macrophages with inhibitors of the IRE1α branch of the UPR. In BMDMs, intracellular curli colocalized with GRP78, a regulator of the UPR. <i>In vivo</i>, acute infection with wild-type STm increased UPR markers in the ceca of HLA-B27tg mice compared to C57BL/6. STm biofilms that contain curli were visible in the lumen of cecal tissue sections. Furthermore, curli was associated with macrophages in the lamina propria, colocalizing with GRP78. Together, these results suggest that UPR plays a role in the curli-induced inflammatory response, especially in the presence of HLA-B27, a possible mechanistic link between STm infection and genetic susceptibility to ReA.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2392877"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of postbiotics on chronic diarrhea in young adults: a randomized, double-blind, placebo-controlled crossover trial assessing clinical symptoms, gut microbiota, and metabolite profiles.","authors":"Shuai Guo, Teng Ma, Lai-Yu Kwok, Keyu Quan, Bohai Li, Huan Wang, Heping Zhang, Bilige Menghe, Yongfu Chen","doi":"10.1080/19490976.2024.2395092","DOIUrl":"10.1080/19490976.2024.2395092","url":null,"abstract":"<p><p>Chronic diarrhea has a considerable impact on quality of life. This randomized, double-blind, placebo-controlled crossover intervention trial was conducted with 69 participants (36 in Group A, 33 in Group B), aiming to investigate the potential of postbiotics in alleviating diarrhea-associated symptoms. Participants received postbiotic Probio-Eco® and placebo for 21 days each in alternating order, with a 14-day washout period between interventions. The results showed that postbiotic intake resulted in significant improvements in Bristol stool scale score, defecation frequency, urgency, and anxiety. Moreover, the postbiotic intervention increased beneficial intestinal bacteria, including <i>Dysosmobacter welbionis</i> and <i>Faecalibacterium prausnitzii</i>, while reducing potential pathogens like <i>Megamonas funiformis</i>. The levels of gut <i>Microviridae</i> notably increased. Non-targeted metabolomics analysis revealed postbiotic-driven enrichment of beneficial metabolites, including α-linolenic acid and p-methoxycinnamic acid, and reduction of diarrhea-associated metabolites, including theophylline, piperine, capsaicin, and phenylalanine. Targeted metabolomics confirmed a significant increase in fecal butyric acid after postbiotic intervention. The levels of aromatic amino acids, phenylalanine and tryptophan, and their related metabolites, 5-hydroxytryptophan and kynurenine, decreased after the postbiotic intervention, suggesting diarrhea alleviation was through modulating the tryptophan-5-hydroxytryptamine and tryptophan-kynurenine pathways. Additionally, chenodeoxycholic acid, a diarrhea-linked primary bile acid, decreased substantially. In conclusion, postbiotics have shown promise in relieving chronic diarrhea.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2395092"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11352714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-01-01Epub Date: 2024-09-23DOI: 10.1080/19490976.2024.2400575
Ipsita Nandi, Rachana Pattani Ramachandran, Deborah E Shalev, Dina Schneidman-Duhovny, Raisa Shtuhin-Rahav, Naomi Melamed-Book, Efrat Zlotkin-Rivkin, Alexander Rouvinski, Ilan Rosenshine, Benjamin Aroeti
{"title":"EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases.","authors":"Ipsita Nandi, Rachana Pattani Ramachandran, Deborah E Shalev, Dina Schneidman-Duhovny, Raisa Shtuhin-Rahav, Naomi Melamed-Book, Efrat Zlotkin-Rivkin, Alexander Rouvinski, Ilan Rosenshine, Benjamin Aroeti","doi":"10.1080/19490976.2024.2400575","DOIUrl":"10.1080/19490976.2024.2400575","url":null,"abstract":"<p><p>Enteropathogenic <i>E. coli</i> (EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulence proteins called effectors into the infected cells. These effectors hijack numerous host processes for the pathogen's benefit. Therefore, studying the mechanisms underlying their action is crucial for a better understanding of the disease. We show that translocated EspH interacts with multiple host Rab GTPases. AlphaFold predictions and site-directed mutagenesis identified glutamic acid and lysine at positions 37 and 41 as Rab interacting residues in EspH. Mutating these sites abolished the ability of EspH to inhibit Akt and mTORC1 signaling, lysosomal exocytosis, and bacterial invasion. Knocking out the endogenous Rab8a gene expression highlighted the involvement of Rab8a in Akt/mTORC1 signaling and lysosomal exocytosis. A phosphoinositide binding domain with a critical tyrosine was identified in EspH. Mutating the tyrosine abolished the localization of EspH at infection sites and its capacity to interact with the Rabs. Our data suggest novel EspH-dependent mechanisms that elicit immune signaling and membrane trafficking during EPEC infection.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2400575"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11421376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-01-01Epub Date: 2024-11-06DOI: 10.1080/19490976.2024.2414796
Miao Yu, Bing Yu, Daiwen Chen
{"title":"The effects of gut microbiota on appetite regulation and the underlying mechanisms.","authors":"Miao Yu, Bing Yu, Daiwen Chen","doi":"10.1080/19490976.2024.2414796","DOIUrl":"10.1080/19490976.2024.2414796","url":null,"abstract":"<p><p>Appetite, a crucial aspect regulated by both the central nervous system and peripheral hormones, is influenced by the composition and dynamics of the intestinal microbiota, as evidenced by recent research. This review highlights the role of intestinal microbiota in appetite regulation, elucidating the involvement of various pathways. Notably, the metabolites generated by intestinal microorganisms, including short-chain fatty acids, bile acids, and amino acid derivatives, play a pivotal role in this intricate process. Furthermore, intestinal microorganisms contribute to appetite regulation by modulating nutritional perception, neural signal transmission, and hormone secretion within the digestive system. Consequently, manipulating and modulating the intestinal microbiota represent innovative strategies for ameliorating appetite-related disorders. This paper provides a comprehensive review of the effects of gut microbes and their metabolites on the central nervous system and host appetite. By exploring their potential regulatory pathways and mechanisms, this study aims to enhance our understanding of how gut microbes influence appetite regulation in the host.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2414796"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-01-01Epub Date: 2024-09-28DOI: 10.1080/19490976.2024.2407047
Laura Avellaneda-Franco, Liang Xie, Michael Nakai, Jeremy J Barr, Francine Z Marques
{"title":"Dietary fiber intake impacts gut bacterial and viral populations in a hypertensive mouse model.","authors":"Laura Avellaneda-Franco, Liang Xie, Michael Nakai, Jeremy J Barr, Francine Z Marques","doi":"10.1080/19490976.2024.2407047","DOIUrl":"10.1080/19490976.2024.2407047","url":null,"abstract":"<p><p>The gut microbiome is an emerging factor in preventing hypertension, yet the influence of gut bacteriophages, viruses infecting bacteria, on this condition remains unclear. Bacteriophage-bacteria interactions, which impact the gut microbiome, are influenced differentially by temperate and virulent bacteriophages. However, the standard technique for studying viral populations, viral-like particles (VLPs)-metagenomes, often overlook prophages, the intracellular stage of temperate bacteriophages, creating a knowledge gap. To address this, we investigated alterations in extracellular and intracellular bacteriophages, alongside bacterial populations, in the angiotensin II-hypertension model. We sequenced VLPs and bulk DNA from cecal-colonic samples collected from male C57BL/6J mice implanted with minipumps containing saline or angiotensin II. We assembled 106 bacterial and 816 viral genomes and found that gut viral and bacterial populations remained stable between hypertensive and normotensive mice. A higher number of temperate viruses were observed across all treatments. Although temperate viruses outnumbered virulent viruses, sequencing of both VLPs and bulk revealed that virions from virulent viruses were more abundant in the murine gut. We then evaluated the impact of low- and high-fiber intake on gut microbiome composition in the angiotensin II model. Fiber intake significantly influenced the gut microbiome composition and hypertension development. Mice receiving high-fiber had lower blood pressure, a higher bacterial-encoded carbohydrate-associated enzyme, and a higher total relative abundance of temperate viruses than those receiving low-fiber. Our findings suggest that phages are not associated with hypertension development in the angiotensin II model. However, they support a complex diet-bacteria/phage interaction that may be involved in blood pressure regulation.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2407047"},"PeriodicalIF":2.9,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-01-01Epub Date: 2024-11-17DOI: 10.1080/19490976.2024.2429754
Lu Yao, Hannah Devotta, Junhui Li, Nonhlanhla Lunjani, Corinna Sadlier, Aonghus Lavelle, Werner C Albrich, Jens Walter, Paul W O'Toole, Liam O'Mahony
{"title":"Dysrupted microbial tryptophan metabolism associates with SARS-CoV-2 acute inflammatory responses and long COVID.","authors":"Lu Yao, Hannah Devotta, Junhui Li, Nonhlanhla Lunjani, Corinna Sadlier, Aonghus Lavelle, Werner C Albrich, Jens Walter, Paul W O'Toole, Liam O'Mahony","doi":"10.1080/19490976.2024.2429754","DOIUrl":"https://doi.org/10.1080/19490976.2024.2429754","url":null,"abstract":"<p><p>Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and risk of long COVID has been associated with the depletion or over-abundance of specific taxa within the gut microbiome. However, the microbial mechanisms mediating these effects are not yet known. We hypothesized that altered microbial production of tryptophan and its downstream derivatives might contribute to inappropriate immune responses to viral infection. In patients hospitalized with COVID-19 (<i>n</i> = 172), serum levels of tryptophan and indole-3-propionate (IPA) negatively correlated with serum levels of many proinflammatory mediators (including C-reactive protein and Serum amyloid A), while C-glycosyltryptophan (C-Trp), indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA) levels were positively correlated with levels of acute phase proteins, proinflammatory cytokines, alarmins and chemokines. A similar pattern was observed in long COVID patients (<i>n</i> = 20) where tryptophan and IPA were negatively associated with a large number of serum cytokines, while C-Trp and IAA were positively associated with circulating cytokine levels. Metagenomic analysis of the fecal microbiota showed the relative abundance of genes encoding the microbial enzymes required for tryptophan production (e.g. anthranilate synthase) and microbial tryptophan metabolism was significantly lower in patients hospitalized with COVID-19 (<i>n</i> = 380) compared to healthy controls (<i>n</i> = 270). Microbial tryptophan metabolites reduced innate cell proinflammatory responses to cytosolic DNA sensor Stimulator of interferon genes (STING), toll-like receptor (TLR)-3 and TLR-4 stimulation <i>in vitro</i>, while IL-10 secretion was enhanced. Microbial tryptophan metabolites also modified <i>ex vivo</i> human lymphocyte responses by limiting the production of TH1 and TH17 associated cytokines, while enhancing secretion of IL-22. These data suggest that lower levels of tryptophan production and tryptophan metabolism by gut microbes may increase the risk of severe and chronic outcomes to SARS-CoV-2 infection due to impaired innate and adaptive responses to infection. Screening patients for lower-level microbiome capacity for tryptophan metabolism may help identify at-risk individuals.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2429754"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-01-01Epub Date: 2024-01-12DOI: 10.1080/19490976.2024.2302076
Mahsa Monshizadeh, Yuzhen Ye
{"title":"Incorporating metabolic activity, taxonomy and community structure to improve microbiome-based predictive models for host phenotype prediction.","authors":"Mahsa Monshizadeh, Yuzhen Ye","doi":"10.1080/19490976.2024.2302076","DOIUrl":"10.1080/19490976.2024.2302076","url":null,"abstract":"<p><p>We developed MicroKPNN, a prior-knowledge guided interpretable neural network for microbiome-based human host phenotype prediction. The prior knowledge used in MicroKPNN includes the metabolic activities of different bacterial species, phylogenetic relationships, and bacterial community structure, all in a shallow neural network. Application of MicroKPNN to seven gut microbiome datasets (involving five different human diseases including inflammatory bowel disease, type 2 diabetes, liver cirrhosis, colorectal cancer, and obesity) shows that incorporation of the prior knowledge helped improve the microbiome-based host phenotype prediction. MicroKPNN outperformed fully connected neural network-based approaches in all seven cases, with the most improvement of accuracy in the prediction of type 2 diabetes. MicroKPNN outperformed a recently developed deep-learning based approach DeepMicro, which selects the best combination of autoencoder and machine learning approach to make predictions, in all of the seven cases. Importantly, we showed that MicroKPNN provides a way for interpretation of the predictive models. Using importance scores estimated for the hidden nodes, MicroKPNN could provide explanations for prior research findings by highlighting the roles of specific microbiome components in phenotype predictions. In addition, it may suggest potential future research directions for studying the impacts of microbiome on host health and diseases. MicroKPNN is publicly available at https://github.com/mgtools/MicroKPNN.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2302076"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10793686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139424637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gut MicrobesPub Date : 2024-01-01Epub Date: 2024-01-18DOI: 10.1080/19490976.2024.2304157
R Forlano, L Martinez-Gili, P Takis, J Miguens-Blanco, T Liu, E Triantafyllou, C Skinner, R Loomba, M Thursz, J R Marchesi, B H Mullish, P Manousou
{"title":"Disruption of gut barrier integrity and host-microbiome interactions underlie MASLD severity in patients with type-2 diabetes mellitus.","authors":"R Forlano, L Martinez-Gili, P Takis, J Miguens-Blanco, T Liu, E Triantafyllou, C Skinner, R Loomba, M Thursz, J R Marchesi, B H Mullish, P Manousou","doi":"10.1080/19490976.2024.2304157","DOIUrl":"10.1080/19490976.2024.2304157","url":null,"abstract":"<p><p>Aberration of the \"gut-liver axis\" contributes to the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we use multi-omics to analyze the gut microbiota composition and metabolic profile of patients with type-2 diabetes mellitus (T2DM). T2DM patients were screened for liver disease by blood tests, ultrasound, and liver stiffness measurements. Stool microbiota was analyzed by 16S rRNA gene sequencing; metabolomic profiling by Nuclear Magnetic Resonance spectroscopy and Ultra-High Performance-Mass Spectrometry. Microbiome and metabolic signatures were analyzed in the whole cohort and in matched subsets to identify signatures specific for steatosis (MASLD±) or fibrosis (Fibrosis±). Gut permeability was assessed <i>in-vitro</i> using monolayers of MDCK cells and trans-epithelial electric resistance (TEER). Cytokine profile was assessed in serum and stools.Overall, 285 patients were enrolled: 255 serum, 252 urine and 97 stool samples were analyzed. <i>Anaeroplasma</i> and <i>Escherichia/Shigella</i> ASVs were higher, while <i>Butyricicoccus</i> ASVs were lower in those with normal liver. In MASLD±, <i>Butyricicoccus</i> ASV was significantly higher in those with steatosis. In the Fibrosis±, <i>Butyricicoccus</i> ASV was significantly lower in those with fibrosis. Glycochenodeoxycholic acid-3-sulfate (G-UDCA-3S) appeared to be higher in MASLD with fibrosis. Fecal water from patients with MASLD and fibrosis caused the greatest drop in the TEER vs those with normal liver; this was reversed with protease inhibitors. Finally, fecal IL-13 was lower in MASLD with fibrosis. We identified microbiome signatures which were specific for steatosis and fibrosis and independent of other metabolic risk factors. Moreover, we conclude that protease-related gut permeability plays a role in those MASLD patients with fibrosis, and that disease progression is linked to a gut-liver axis which is at least partially independent of T2DM.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2304157"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10798360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}