Pub Date : 2024-10-16DOI: 10.1080/19490976.2024.2416517
Francesco Vacca, Thomas C. Mules, Mali Camberis, Brittany Lavender, Sophia-Louise Noble, Alissa Cait, Kate Maclean, John Mamum, Bibek Yumnam, Tama Te Kawa, Laura Ferrer-Font, Jeffry S. Tang, Olivier Gasser, Graham Le Gros, Stephen Inns
Infecting humans with controlled doses of helminths, such as human hookworm (termed hookworm therapy), is proposed to prevent or treat various intestinal and extraintestinal diseases. However, full...
{"title":"Controlled infection with cryopreserved human hookworm induces CTLA-4 expression on Tregs and upregulates tryptophan metabolism","authors":"Francesco Vacca, Thomas C. Mules, Mali Camberis, Brittany Lavender, Sophia-Louise Noble, Alissa Cait, Kate Maclean, John Mamum, Bibek Yumnam, Tama Te Kawa, Laura Ferrer-Font, Jeffry S. Tang, Olivier Gasser, Graham Le Gros, Stephen Inns","doi":"10.1080/19490976.2024.2416517","DOIUrl":"https://doi.org/10.1080/19490976.2024.2416517","url":null,"abstract":"Infecting humans with controlled doses of helminths, such as human hookworm (termed hookworm therapy), is proposed to prevent or treat various intestinal and extraintestinal diseases. However, full...","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"28 1","pages":""},"PeriodicalIF":12.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439812","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}
Pub Date : 2024-10-16DOI: 10.1080/19490976.2024.2412676
Elena Fekete,Thibault Allain,Olivia Sosnowski,Stephanie Anderson,Ian A Lewis,Andre G Buret
Infection with the protozoan parasite Giardia duodenalis (syn. intestinalis, lamblia) has been associated with intestinal mucus disruptions and microbiota dysbiosis. The mechanisms remain incompletely understood. Mucus consists primarily of densely glycosylated mucin glycoproteins. Mucin O-glycans influence mucus barrier properties and mucin-microbe interactions and are frequently altered during disease. In this study, we observed time-dependent and regiospecific alterations to intestinal mucin glycosylation patterns and the expression of mucin-associated glycosyltransferase genes during Giardia infection. Glycosylation alterations were observed in Giardia-infected mice in the upper small intestine, the site of parasite colonization, and in the distal colon, where active trophozoites were absent. Alterations occurred as early as day 2 post-infection and persisted in mice after parasite clearance. We also observed small intestinal goblet cell hyperplasia and thinning of the distal colon mucus barrier during early infection, and microbiota alterations and altered production of cecal SCFAs. Giardia-induced alterations to mucin glycosylation were at least in part dependent on microbiota dysbiosis, as transplantation of a dysbiotic mucosal microbiota collected from Giardia-infected mice recapitulated some alterations. This study describes a novel mechanism by which Giardia alters intestinal mucin glycosylation, and implicates the small intestinal microbiota in regulation of mucin glycosylation patterns throughout the gastrointestinal tract.
感染十二指肠贾第虫（Giardia duodenalis，同肠贾第虫，lamblia）原生寄生虫与肠粘液紊乱和微生物群失调有关。其机理尚不完全清楚。粘液主要由密集糖基化的粘蛋白糖蛋白组成。粘蛋白 O 型糖影响粘液屏障特性和粘蛋白与微生物的相互作用，并经常在疾病期间发生改变。在这项研究中，我们观察到在贾第虫感染期间，肠道粘蛋白糖基化模式和粘蛋白相关糖基转移酶基因的表达发生了时间依赖性和区域特异性改变。贾第虫感染小鼠的小肠上部（寄生虫定植的部位）和结肠远端（没有活跃的滋养体）都观察到了糖基化改变。这种变化最早发生在感染后第 2 天，寄生虫被清除后仍在小鼠体内持续存在。在早期感染期间，我们还观察到小肠上皮细胞增生和远端结肠粘液屏障变薄，以及微生物群改变和盲肠 SCFAs 生成改变。贾第虫诱导的粘蛋白糖基化改变至少部分依赖于微生物群失调，因为移植从贾第虫感染小鼠体内收集的失调粘膜微生物群可重现某些改变。这项研究描述了贾第虫改变肠道粘蛋白糖基化的新机制，并指出小肠微生物群与整个胃肠道粘蛋白糖基化模式的调控有关。
{"title":"Giardia spp.-induced microbiota dysbiosis disrupts intestinal mucin glycosylation.","authors":"Elena Fekete,Thibault Allain,Olivia Sosnowski,Stephanie Anderson,Ian A Lewis,Andre G Buret","doi":"10.1080/19490976.2024.2412676","DOIUrl":"https://doi.org/10.1080/19490976.2024.2412676","url":null,"abstract":"Infection with the protozoan parasite Giardia duodenalis (syn. intestinalis, lamblia) has been associated with intestinal mucus disruptions and microbiota dysbiosis. The mechanisms remain incompletely understood. Mucus consists primarily of densely glycosylated mucin glycoproteins. Mucin O-glycans influence mucus barrier properties and mucin-microbe interactions and are frequently altered during disease. In this study, we observed time-dependent and regiospecific alterations to intestinal mucin glycosylation patterns and the expression of mucin-associated glycosyltransferase genes during Giardia infection. Glycosylation alterations were observed in Giardia-infected mice in the upper small intestine, the site of parasite colonization, and in the distal colon, where active trophozoites were absent. Alterations occurred as early as day 2 post-infection and persisted in mice after parasite clearance. We also observed small intestinal goblet cell hyperplasia and thinning of the distal colon mucus barrier during early infection, and microbiota alterations and altered production of cecal SCFAs. Giardia-induced alterations to mucin glycosylation were at least in part dependent on microbiota dysbiosis, as transplantation of a dysbiotic mucosal microbiota collected from Giardia-infected mice recapitulated some alterations. This study describes a novel mechanism by which Giardia alters intestinal mucin glycosylation, and implicates the small intestinal microbiota in regulation of mucin glycosylation patterns throughout the gastrointestinal tract.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"24 1","pages":"2412676"},"PeriodicalIF":12.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443735","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}
High-fat diet (HFD) has been linked to female infertility. However, the specific age at which HFD impacts ovarian function and the underlying mechanisms remain poorly understood. Here, we administered a HFD to female mice at various developmental stages: pre-puberty (4 weeks old), post-puberty (6 weeks old), young adult (9 weeks old), and middle age (32 weeks old). Our observations indicated that ovarian function was most significantly compromised when HFD was initiated at post-puberty. Consequently, post-puberty mice were chosen for further investigation. Through transplantation of fecal bacteria from the HFD mice to the mice on a normal diet, we confirmed that gut microbiota dysbiosis contributed to HFD-induced deteriorated fertility and disrupted estradiol synthesis. Utilizing untargeted and targeted metabolomics analyses, we identified L-saccharopine as a key metabolite, which was enriched in the feces, serum, and ovaries of HFD and HFD-FMT mice. Subsequent in vitro and in vivo experiments demonstrated that L-saccharopine disrupted mitochondrial homeostasis by impeding AMPKα/MFF-mediated mitochondrial fission. This disruption ultimately hindered estradiol synthesis and compromised oocyte quality. AICAR, an activator of AMPKα, ameliorated L-saccharopine induced mitochondrial damage in granulosa cells and oocytes, thereby enhancing E2 synthesis and improving oocyte quality. Collectively, our findings indicate that the accumulation of L-saccharopine may play a pivotal role in mediating HFD-induced ovarian dysfunction. This highlights the potential therapeutic benefits of targeting the gut microbiota-metabolite-ovary axis to address HFD-induced ovarian dysfunction.
{"title":"High-fat diet-induced L-saccharopine accumulation inhibits estradiol synthesis and damages oocyte quality by disturbing mitochondrial homeostasis.","authors":"Jingyi Wen,Yanzhi Feng,Liru Xue,Suzhen Yuan,Qian Chen,Aiyue Luo,Shixuan Wang,Jinjin Zhang","doi":"10.1080/19490976.2024.2412381","DOIUrl":"https://doi.org/10.1080/19490976.2024.2412381","url":null,"abstract":"High-fat diet (HFD) has been linked to female infertility. However, the specific age at which HFD impacts ovarian function and the underlying mechanisms remain poorly understood. Here, we administered a HFD to female mice at various developmental stages: pre-puberty (4 weeks old), post-puberty (6 weeks old), young adult (9 weeks old), and middle age (32 weeks old). Our observations indicated that ovarian function was most significantly compromised when HFD was initiated at post-puberty. Consequently, post-puberty mice were chosen for further investigation. Through transplantation of fecal bacteria from the HFD mice to the mice on a normal diet, we confirmed that gut microbiota dysbiosis contributed to HFD-induced deteriorated fertility and disrupted estradiol synthesis. Utilizing untargeted and targeted metabolomics analyses, we identified L-saccharopine as a key metabolite, which was enriched in the feces, serum, and ovaries of HFD and HFD-FMT mice. Subsequent in vitro and in vivo experiments demonstrated that L-saccharopine disrupted mitochondrial homeostasis by impeding AMPKα/MFF-mediated mitochondrial fission. This disruption ultimately hindered estradiol synthesis and compromised oocyte quality. AICAR, an activator of AMPKα, ameliorated L-saccharopine induced mitochondrial damage in granulosa cells and oocytes, thereby enhancing E2 synthesis and improving oocyte quality. Collectively, our findings indicate that the accumulation of L-saccharopine may play a pivotal role in mediating HFD-induced ovarian dysfunction. This highlights the potential therapeutic benefits of targeting the gut microbiota-metabolite-ovary axis to address HFD-induced ovarian dysfunction.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"66 1","pages":"2412381"},"PeriodicalIF":12.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443736","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}
Pub Date : 2024-10-14DOI: 10.1080/19490976.2024.2412669
Felix F Krause,Kira I Mangold,Anna-Lena Ruppert,Hanna Leister,Anne Hellhund-Zingel,Aleksandra Lopez Krol,Jelena Pesek,Bernhard Watzer,Sarah Winterberg,Hartmann Raifer,Kai Binder,Ralf Kinscherf,Alesia Walker,Wolfgang A Nockher,R Verena Taudte,Wilhelm Bertrams,Bernd Schmeck,Anja A Kühl,Britta Siegmund,Rossana Romero,Maik Luu,Stephan Göttig,Isabelle Bekeredjian-Ding,Ulrich Steinhoff,Burkhard Schütz,Alexander Visekruna
Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).
{"title":"Clostridium sporogenes-derived metabolites protect mice against colonic inflammation.","authors":"Felix F Krause,Kira I Mangold,Anna-Lena Ruppert,Hanna Leister,Anne Hellhund-Zingel,Aleksandra Lopez Krol,Jelena Pesek,Bernhard Watzer,Sarah Winterberg,Hartmann Raifer,Kai Binder,Ralf Kinscherf,Alesia Walker,Wolfgang A Nockher,R Verena Taudte,Wilhelm Bertrams,Bernd Schmeck,Anja A Kühl,Britta Siegmund,Rossana Romero,Maik Luu,Stephan Göttig,Isabelle Bekeredjian-Ding,Ulrich Steinhoff,Burkhard Schütz,Alexander Visekruna","doi":"10.1080/19490976.2024.2412669","DOIUrl":"https://doi.org/10.1080/19490976.2024.2412669","url":null,"abstract":"Gut microbiota-derived metabolites play a pivotal role in the maintenance of intestinal immune homeostasis. Here, we demonstrate that the human commensal Clostridium sporogenes possesses a specific metabolic fingerprint, consisting predominantly of the tryptophan catabolite indole-3-propionic acid (IPA), the branched-chain acids (BCFAs) isobutyrate and isovalerate and the short-chain fatty acids (SCFAs) acetate and propionate. Mono-colonization of germ-free mice with C. sporogenes (CS mice) affected colonic mucosal immune cell phenotypes, including up-regulation of Il22 gene expression, and increased abundance of transcriptionally active colonic tuft cells and Foxp3+ regulatory T cells (Tregs). In DSS-induced colitis, conventional mice suffered severe inflammation accompanied by loss of colonic crypts. These symptoms were absent in CS mice. In conventional, but not CS mice, bulk RNAseq analysis of the colon revealed an increase in inflammatory and Th17-related gene signatures. C. sporogenes-derived IPA reduced IL-17A protein expression by suppressing mTOR activity and by altering ribosome-related pathways in Th17 cells. Additionally, BCFAs and SCFAs generated by C. sporogenes enhanced the activity of Tregs and increased the production of IL-22, which led to protection from colitis. Collectively, we identified C. sporogenes as a therapeutically relevant probiotic bacterium that might be employed in patients with inflammatory bowel disease (IBD).","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"23 1","pages":"2412669"},"PeriodicalIF":12.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436105","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}
Metabolic syndrome (MetS) is a cluster of several human conditions including abdominal obesity, hypertension, dyslipidemia, and hyperglycemia, all of which are risk factors of type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). Dietary pattern is a well-recognized MetS risk factor, but additional changes related to the modern Western life-style may also contribute to MetS. Here we hypothesize that the disappearance of amoebas in the gut plays a role in the emergence of MetS in association with dietary changes. Four groups of C57B/6J mice fed with a high-fat diet (HFD) or a normal diet (ND) were colonized or not with Entamoeba muris, a commensal amoeba. Seventy days after inoculation, cecal microbiota, and bile acid compositions were analyzed by high-throughput sequencing of 16S rDNA and mass spectrometry, respectively. Cytokine concentrations were measured in the gut, liver, and mesenteric fat looking for low-grade inflammation. The impact of HFD on liver metabolic dysfunction was explored by Oil Red O staining, triglycerides, cholesterol concentrations, and the expression of genes involved in β-oxidation and lipogenesis. Colonization with E. muris had a beneficial impact, with a reduction in dysbiosis, lower levels of fecal secondary bile acids, and an improvement in hepatic steatosis, arguing for a protective role of commensal amoebas in MetS and more specifically HFD-associated MASLD.
{"title":"Entamoeba muris mitigates metabolic consequences of high-fat diet in mice.","authors":"Maryline Roy,Anne Dumay,Sandrine Adiba,Sylvana Rozes,Seiki Kobayashi,Valérie Paradis,Catherine Postic,Dominique Rainteau,Eric Ogier-Denis,Maud Le Gall,Ulrich Meinzer,Emilie Viennois,Maite Casado-Bedmar,Alexis Mosca,Jean-Pierre Hugot","doi":"10.1080/19490976.2024.2409210","DOIUrl":"https://doi.org/10.1080/19490976.2024.2409210","url":null,"abstract":"Metabolic syndrome (MetS) is a cluster of several human conditions including abdominal obesity, hypertension, dyslipidemia, and hyperglycemia, all of which are risk factors of type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). Dietary pattern is a well-recognized MetS risk factor, but additional changes related to the modern Western life-style may also contribute to MetS. Here we hypothesize that the disappearance of amoebas in the gut plays a role in the emergence of MetS in association with dietary changes. Four groups of C57B/6J mice fed with a high-fat diet (HFD) or a normal diet (ND) were colonized or not with Entamoeba muris, a commensal amoeba. Seventy days after inoculation, cecal microbiota, and bile acid compositions were analyzed by high-throughput sequencing of 16S rDNA and mass spectrometry, respectively. Cytokine concentrations were measured in the gut, liver, and mesenteric fat looking for low-grade inflammation. The impact of HFD on liver metabolic dysfunction was explored by Oil Red O staining, triglycerides, cholesterol concentrations, and the expression of genes involved in β-oxidation and lipogenesis. Colonization with E. muris had a beneficial impact, with a reduction in dysbiosis, lower levels of fecal secondary bile acids, and an improvement in hepatic steatosis, arguing for a protective role of commensal amoebas in MetS and more specifically HFD-associated MASLD.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"56 1","pages":"2409210"},"PeriodicalIF":12.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436106","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}
Pub Date : 2024-10-12DOI: 10.1080/19490976.2024.2415490
Madeline Krieger,Mingzhe Guo,Justin Merritt
The Gram-negative anaerobic species Fusobacterium nucleatum was originally described as a commensal organism from the human oral microbiome. However, it is now widely recognized as a key inflammophilic pathobiont associated with a wide variety of oral and extraoral diseases. Historically, F. nucleatum has been classified into four subspecies that have been generally considered as functionally interchangeable in their pathogenic potential. Recent studies have challenged this notion, as clinical data reveal a highly biased distribution of F. nucleatum subspecies within disease sites of both inflammatory oral diseases and various malignancies. This review details the historical basis for the F. nucleatum subspecies designations and summarizes our current understanding of the similarities and distinctions between these organisms to provide important context for future clinical and laboratory studies of F. nucleatum.
{"title":"Reexamining the role of Fusobacterium nucleatum subspecies in clinical and experimental studies.","authors":"Madeline Krieger,Mingzhe Guo,Justin Merritt","doi":"10.1080/19490976.2024.2415490","DOIUrl":"https://doi.org/10.1080/19490976.2024.2415490","url":null,"abstract":"The Gram-negative anaerobic species Fusobacterium nucleatum was originally described as a commensal organism from the human oral microbiome. However, it is now widely recognized as a key inflammophilic pathobiont associated with a wide variety of oral and extraoral diseases. Historically, F. nucleatum has been classified into four subspecies that have been generally considered as functionally interchangeable in their pathogenic potential. Recent studies have challenged this notion, as clinical data reveal a highly biased distribution of F. nucleatum subspecies within disease sites of both inflammatory oral diseases and various malignancies. This review details the historical basis for the F. nucleatum subspecies designations and summarizes our current understanding of the similarities and distinctions between these organisms to provide important context for future clinical and laboratory studies of F. nucleatum.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"1 1","pages":"2415490"},"PeriodicalIF":12.2,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431119","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}
Pub Date : 2024-10-12DOI: 10.1080/19490976.2024.2415488
Anna Sayol-Altarriba,Andrea Aira,Anna Villasante,Rosa Albarracín,Joana Faneca,Gregori Casals,José Luis Villanueva-Cañas,Climent Casals-Pascual
Short-chain fatty acids (SCFAs) represent a cornerstone of gut health, serving as critical mediators of immune modulation and overall host homeostasis. Patients with dysbiosis caused by Clostridioides difficile infection (CDI) typically exhibit lower SCFAs levels compared to healthy stool donors and, thus, the concentration of SCFAs has been proposed as a proxy marker of a healthy microbiota. However, there is no consistency in the methods used to quantify SCFAs in stool samples and usually, the results are normalized by the weight of the stool samples, which does not address differences in water and fiber content and ignores bacterial counts in the sample (the main component of stool that contributes to the composition of these metabolites in the sample). Here, we show that normalized SCFAs concentrations by the bacterial count improve discrimination between healthy and dysbiotic samples (patients with CDI), particularly when using acetate and propionate levels. After normalization, butyrate is the metabolite that best discriminates eubiotic and dysbiotic samples according to the area under the receiver operating characteristic (ROC) curve (AUC-ROC = 0.860, [95% CI: 0.786-0.934], p < .0001).
{"title":"Normalization of short-chain fatty acid concentration by bacterial count of stool samples improves discrimination between eubiotic and dysbiotic gut microbiota caused by Clostridioides difficile infection.","authors":"Anna Sayol-Altarriba,Andrea Aira,Anna Villasante,Rosa Albarracín,Joana Faneca,Gregori Casals,José Luis Villanueva-Cañas,Climent Casals-Pascual","doi":"10.1080/19490976.2024.2415488","DOIUrl":"https://doi.org/10.1080/19490976.2024.2415488","url":null,"abstract":"Short-chain fatty acids (SCFAs) represent a cornerstone of gut health, serving as critical mediators of immune modulation and overall host homeostasis. Patients with dysbiosis caused by Clostridioides difficile infection (CDI) typically exhibit lower SCFAs levels compared to healthy stool donors and, thus, the concentration of SCFAs has been proposed as a proxy marker of a healthy microbiota. However, there is no consistency in the methods used to quantify SCFAs in stool samples and usually, the results are normalized by the weight of the stool samples, which does not address differences in water and fiber content and ignores bacterial counts in the sample (the main component of stool that contributes to the composition of these metabolites in the sample). Here, we show that normalized SCFAs concentrations by the bacterial count improve discrimination between healthy and dysbiotic samples (patients with CDI), particularly when using acetate and propionate levels. After normalization, butyrate is the metabolite that best discriminates eubiotic and dysbiotic samples according to the area under the receiver operating characteristic (ROC) curve (AUC-ROC = 0.860, [95% CI: 0.786-0.934], p < .0001).","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"33 1","pages":"2415488"},"PeriodicalIF":12.2,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431120","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}
The interplay between the human microbiome and the musculoskeletal system represents a burgeoning field of research with profound implications for understanding and treating musculoskeletal disorders. This review articulates the pivotal role of the microbiome in modulating bone health, highlighting the gut-bone axis as a critical nexus for potential therapeutic intervention. Through a meticulous analysis of recent clinical research, we underscore the microbiome's influence on osteoporosis, sarcopenia, osteoarthritis, and rheumatoid arthritis, delineating both the direct and indirect mechanisms by which microbiota could impact musculoskeletal integrity and function. Our investigation reveals novel insights into the microbiota's contribution to bone density regulation, hormone production, immune modulation, and nutrient absorption, laying the groundwork for innovative microbiome-based strategies in musculoskeletal disease management. Significantly, we identify the challenges hindering the translation of research into clinical practice, including the limitations of current microbial sequencing techniques and the need for standardized methodologies in microbiome studies. Furthermore, we highlight promising directions for future research, particularly in the realm of personalized medicine, where the microbiome's variability offers unique opportunities for tailored treatment approaches. This review sets a new agenda for leveraging gut microbiota in the diagnosis, prevention, and treatment of musculoskeletal conditions, marking a pivotal step toward integrating microbiome science into clinical musculoskeletal care.
{"title":"Microbiome's role in musculoskeletal health through the gut-bone axis insights.","authors":"Zhengrui Li,Qi Wang,Xufeng Huang,Yinteng Wu,Dan Shan","doi":"10.1080/19490976.2024.2410478","DOIUrl":"https://doi.org/10.1080/19490976.2024.2410478","url":null,"abstract":"The interplay between the human microbiome and the musculoskeletal system represents a burgeoning field of research with profound implications for understanding and treating musculoskeletal disorders. This review articulates the pivotal role of the microbiome in modulating bone health, highlighting the gut-bone axis as a critical nexus for potential therapeutic intervention. Through a meticulous analysis of recent clinical research, we underscore the microbiome's influence on osteoporosis, sarcopenia, osteoarthritis, and rheumatoid arthritis, delineating both the direct and indirect mechanisms by which microbiota could impact musculoskeletal integrity and function. Our investigation reveals novel insights into the microbiota's contribution to bone density regulation, hormone production, immune modulation, and nutrient absorption, laying the groundwork for innovative microbiome-based strategies in musculoskeletal disease management. Significantly, we identify the challenges hindering the translation of research into clinical practice, including the limitations of current microbial sequencing techniques and the need for standardized methodologies in microbiome studies. Furthermore, we highlight promising directions for future research, particularly in the realm of personalized medicine, where the microbiome's variability offers unique opportunities for tailored treatment approaches. This review sets a new agenda for leveraging gut microbiota in the diagnosis, prevention, and treatment of musculoskeletal conditions, marking a pivotal step toward integrating microbiome science into clinical musculoskeletal care.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"23 1","pages":"2410478"},"PeriodicalIF":12.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436108","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}
Pub Date : 2024-10-08DOI: 10.1080/19490976.2024.2412376
Do-Yeon Kim,So-Yeon Lee,Jae-Yun Lee,Tae Woong Whon,June-Young Lee,Che Ok Jeon,Jin-Woo Bae
The human intestine hosts a complex ecosystem of various microorganisms, collectively known as the gut microbiome, which significantly impacts human health. Disruptions in the gut microbiome are linked to various disorders, including gastrointestinal diseases, such as Clostridioides difficile infection and inflammatory bowel disease, as well as metabolic, neurological, oncologic conditions. Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as prospective therapeutic procedures to restore microbial and metabolic balance in the gut. This review assesses the latest advancements, challenges, and therapeutic efficacy of FMT and LBPs, highlighting the need for standardization, safety, and long-term evaluation to optimize their clinical application.
{"title":"Gut microbiome therapy: fecal microbiota transplantation vs live biotherapeutic products.","authors":"Do-Yeon Kim,So-Yeon Lee,Jae-Yun Lee,Tae Woong Whon,June-Young Lee,Che Ok Jeon,Jin-Woo Bae","doi":"10.1080/19490976.2024.2412376","DOIUrl":"https://doi.org/10.1080/19490976.2024.2412376","url":null,"abstract":"The human intestine hosts a complex ecosystem of various microorganisms, collectively known as the gut microbiome, which significantly impacts human health. Disruptions in the gut microbiome are linked to various disorders, including gastrointestinal diseases, such as Clostridioides difficile infection and inflammatory bowel disease, as well as metabolic, neurological, oncologic conditions. Fecal microbiota transplantation (FMT) and live biotherapeutic products (LBPs) have emerged as prospective therapeutic procedures to restore microbial and metabolic balance in the gut. This review assesses the latest advancements, challenges, and therapeutic efficacy of FMT and LBPs, highlighting the need for standardization, safety, and long-term evaluation to optimize their clinical application.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"20 1","pages":"2412376"},"PeriodicalIF":12.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385144","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}
Pub Date : 2024-10-07DOI: 10.1080/19490976.2024.2405547
Emilie Steinbach, Eugeni Belda, Rohia Alili, Solia Adriouch, Charlène J. G. Dauriat, Gianfranco Donatelli, Jean-Loup Dumont, Filippo Pacini, Thierry Tuszynski, Véronique Pelloux, Flavien Jacques, Laura Creusot, Emavieve Coles, Paul Taillandier, Marta Vazquez Gomez, Davide Masi, Véronique Mateo, Sébastien André, Melissa Kordahi, Christine Rouault, Jean-Daniel Zucker, Harry Sokol, Laurent Genser, Benoit Chassaing, Tiphaine Le Roy, Karine Clément
The intestinal microbiota is increasingly recognized as a crucial player in the development and maintenance of various chronic conditions, including obesity and associated metabolic diseases. While...
{"title":"Comparative analysis of the duodenojejunal microbiome with the oral and fecal microbiomes reveals its stronger association with obesity and nutrition","authors":"Emilie Steinbach, Eugeni Belda, Rohia Alili, Solia Adriouch, Charlène J. G. Dauriat, Gianfranco Donatelli, Jean-Loup Dumont, Filippo Pacini, Thierry Tuszynski, Véronique Pelloux, Flavien Jacques, Laura Creusot, Emavieve Coles, Paul Taillandier, Marta Vazquez Gomez, Davide Masi, Véronique Mateo, Sébastien André, Melissa Kordahi, Christine Rouault, Jean-Daniel Zucker, Harry Sokol, Laurent Genser, Benoit Chassaing, Tiphaine Le Roy, Karine Clément","doi":"10.1080/19490976.2024.2405547","DOIUrl":"https://doi.org/10.1080/19490976.2024.2405547","url":null,"abstract":"The intestinal microbiota is increasingly recognized as a crucial player in the development and maintenance of various chronic conditions, including obesity and associated metabolic diseases. While...","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"55 1","pages":""},"PeriodicalIF":12.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383806","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}
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