Gut Microbes最新文献

{"title":"Adaptation to tolerate high doses of arabinoxylan is associated with fecal levels of <i>Bifidobacterium longum</i>.","authors":"Edward C Deehan, Zhengxiao Zhang, Nguyen K Nguyen, Maria Elisa Perez-Muñoz, Janis Cole, Alessandra Riva, David Berry, Carla M Prado, Jens Walter","doi":"10.1080/19490976.2024.2363021","DOIUrl":"10.1080/19490976.2024.2363021","url":null,"abstract":"<p><p>Dietary fiber supplements are a strategy to close the 'fiber gap' and induce targeted modulations of the gut microbiota. However, higher doses of fiber supplements cause gastrointestinal (GI) symptoms that differ among individuals. What determines these inter-individual differences is insufficiently understood. Here we analyzed findings from a six-week randomized controlled trial that evaluated GI symptoms to corn bran arabinoxylan (AX; <i>n</i> = 15) relative to non-fermentable microcrystalline cellulose (MCC; <i>n</i> = 16) at efficacious supplement doses of 25 g/day (females) or 35 g/day (males) in adults with excess weight. Self-reported flatulence, bloating, and stomach aches were evaluated weekly. Bacterial taxa involved in AX fermentation were identified by bioorthogonal non-canonical amino acid tagging. Associations between GI symptoms, fecal microbiota features, and diet history were systematically investigated. AX supplementation increased symptoms during the first three weeks relative to MCC (<i>p</i> < 0.05, Mann-Whitney tests), but subjects 'adapted' with symptoms reverting to baseline levels toward the end of treatment. Symptom adaptations were individualized and correlated with the relative abundance of <i>Bifidobacterium longum</i> at baseline (r_s = 0.74, <i>p</i> = 0.002), within the bacterial community that utilized AX (r_s = 0.69, <i>p</i> = 0.006), and AX-induced shifts in acetate (r_s = 0.54, <i>p</i> = 0.039). Lower baseline consumption of animal-based foods and higher whole grains associated with less severity and better adaptation. These findings suggest that humans do 'adapt' to tolerate efficacious fiber doses, and this process is linked to their microbiome and dietary factors known to interact with gut microbes, providing a basis for the development of strategies for improved tolerance of dietary fibers.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2363021"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300559","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":"Association between gut microbiota and CpG island methylator phenotype in colorectal cancer.","authors":"Pyoung Hwa Park, Kelsey Keith, Gennaro Calendo, Jaroslav Jelinek, Jozef Madzo, Raad Z Gharaibeh, Jayashri Ghosh, Carmen Sapienza, Christian Jobin, Jean-Pierre J Issa","doi":"10.1080/19490976.2024.2363012","DOIUrl":"10.1080/19490976.2024.2363012","url":null,"abstract":"<p><p>The intestinal microbiota is an important environmental factor implicated in CRC development. Intriguingly, modulation of DNA methylation by gut microbiota has been reported in preclinical models, although the relationship between tumor-infiltrating bacteria and CIMP status is currently unexplored. In this study, we investigated tumor-associated bacteria in 203 CRC tumor cases and validated the findings using The Cancer Genome Atlas datasets. We assessed the abundance of <i>Bacteroides fragilis</i>, <i>Escherichia coli</i>, <i>Fusobacterium nucleatum</i>, and <i>Klebsiella pneumoniae</i> through qPCR analysis and observed enrichment of all four bacterial species in CRC samples. Notably, except for <i>E. coli</i>, all exhibited significant enrichment in cases of CIMP. This enrichment was primarily driven by a subset of cases distinguished by high levels of these bacteria, which we labeled as \"Superhigh\". The bacterial Superhigh status showed a significant association with CIMP (odds ratio 3.1, p-value = 0.013) and with <i>MLH1</i> methylation (odds ratio 4.2, p-value = 0.0025). In TCGA CRC cases (393 tumor and 45 adj. normal), bacterial taxa information was extracted from non-human whole exome sequencing reads, and the bacterial Superhigh status was similarly associated with CIMP (odds ratio 2.9, <i>p</i> < 0.001) and <i>MLH1</i> methylation (odds ratio 3.5, <i>p</i> < 0.001). Finally, 16S ribosomal RNA gene sequencing revealed high enrichment of <i>Bergeyella spp</i>. <i>C. concisus</i>, and <i>F. canifelinum</i> in CIMP-Positive tumor cases. Our findings highlight that specific bacterial taxa may influence DNA methylation, particularly in CpG islands, and contribute to the development and progression of CIMP in colorectal cancer.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2363012"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300560","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":"Probiotics and microbial metabolites maintain barrier and neuromuscular functions and clean protein aggregation to delay disease progression in TDP43 mutation mice.","authors":"Yongguo Zhang, Yinglin Xia, Jun Sun","doi":"10.1080/19490976.2024.2363880","DOIUrl":"10.1080/19490976.2024.2363880","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease. The ALS mice expressing human mutant of transactive response DNA binding protein of 43 kDa (hmTDP43) showed intestinal dysfunction before neuromuscular symptoms. We hypothesize that restoring the intestinal and microbial homeostasis with a bacterial metabolite or probiotics delays the ALS disease onset. We investigate the pathophysiological changes in the intestine and neurons, intestinal and blood-brain barriers, and inflammation during the ALS progression. We then cultured enteric glial cells (EGCs) isolated from TDP43 mice for mechanistic studies. TDP43 mice had significantly decreased intestinal mobility, increased permeability, and weakened muscle, compared with the age-matched wild-type mice. We observed increased hmTDP43 and Glial fibrillary acidic protein (GFAP), and decreased expression of α-smooth muscle actin (α-SMA), tight junction proteins (ZO-1 and Claudin-5) in the colon, spinal cord, and brain in TDP43 mice. TDP43 mice had reduced Butyryl-coenzyme A CoA transferase, decreased butyrate-producing bacteria <i>Butyrivibrio fibrisolvens</i>, and increased <i>Bacteroides fragilis</i>, compared to the WT mice. Serum inflammation cytokines (IL-6, IL-17, and IFN-γ) and LPS were elevated in TDP43 mice. EGCs from TDP43 mice showed aggregation of hmTDP43 associated with increased GFAP and ionized calcium-binding adaptor molecule (IBA1, a microglia marker). TDP43 mice treated with butyrate or probiotic VSL#3 had significantly increased rotarod time, increased intestinal mobility and decreased permeability, compared to the untreated group. Butyrate or probiotics treatment decreased the expression of GFAP, TDP43, and increased α-SMA, ZO-1, and Claudin-5 in the colon, spinal cord, and brain. Also, butyrate or probiotics treatment enhanced the Butyryl-coenzyme A CoA transferase, <i>Butyrivibrio fibrisolvens</i>, and reduced inflammatory cytokines in TDP43 mice. The TDP43 EGCs treated with butyrate or probiotics showed reduced GFAP, IBA1, and TDP43 aggregation. Restoring the intestinal and microbial homeostasis by beneficial bacteria and metabolites provide a potential therapeutic strategy to treat ALS.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2363880"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300562","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":"Restricted intake of sulfur-containing amino acids reversed the hepatic injury induced by excess <i>Desulfovibrio</i> through gut-liver axis.","authors":"Lingxi Zhou, Gexue Lu, Yawen Nie, Yilin Ren, Jin-Song Shi, Yuzheng Xue, Zheng-Hong Xu, Yan Geng","doi":"10.1080/19490976.2024.2370634","DOIUrl":"10.1080/19490976.2024.2370634","url":null,"abstract":"<p><p>Diet is a key player in gut-liver axis. However, the effect of different dietary patterns on gut microbiota and liver functions remains unclear. Here, we used rodent standard chow and purified diet to mimic two common human dietary patterns: grain and plant-based diet and refined-food-based diet, respectively and explored their impacts on gut microbiota and liver. Gut microbiota experienced a great shift with notable increase in <i>Desulfovibrio</i>, gut bile acid (BA) levels elevated significantly, and liver inflammation was observed in mice fed with the purified diet. Liver inflammation and elevated gut BA levels also occurred in mice fed with the chow diet after receiving <i>Desulfovibrio desulfuricans</i> ATCC 29,577 (DSV). Restriction of sulfur-containing amino acids (SAAs) prevented liver injury mainly through higher hepatic antioxidant and detoxifying ability and reversed the elevated BA levels due to excess <i>Desulfovibrio</i>. <i>Ex vivo</i> fermentation of human fecal microbiota with primary BAs demonstrated that DSV enhanced production of secondary BAs. Higher concentration of both primary and secondary BAs were found in the gut of germ-free mice after receiving DSV. In conclusion, Restriction of SAAs in diet may become an effective dietary intervention to prevent liver injury associated with excess <i>Desulfovibrio</i> in the gut.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2370634"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467526","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":"Quinic acid alleviates high-fat diet-induced neuroinflammation by inhibiting DR3/IKK/NF-κB signaling via gut microbial tryptophan metabolites.","authors":"Sen Li, Yuwei Cai, Tong Guan, Yu Zhang, Kai Huang, Ze Zhang, Wangqing Cao, Xiao Guan","doi":"10.1080/19490976.2024.2374608","DOIUrl":"10.1080/19490976.2024.2374608","url":null,"abstract":"<p><p>With the increasing of aging population and the consumption of high-fat diets (HFD), the incidence of Alzheimer's disease (AD) has skyrocketed. Natural antioxidants show promising potential in the prevention of AD, as oxidative stress and neuroinflammation are two hallmarks of AD pathogenesis. Here, we showed that quinic acid (QA), a polyphenol derived from millet, significantly decreased HFD-induced brain oxidative stress and neuroinflammation and the levels of Aβ and p-Tau. Examination of gut microbiota suggested the improvement of the composition of gut microbiota in HFD mice after QA treatment. Metabolomic analysis showed significant increase of gut microbial tryptophan metabolites indole-3-acetic acid (IAA) and kynurenic acid (KYNA) by QA. In addition, IAA and KYNA showed negative correlation with pro-inflammatory factors and AD indicators. Further experiments on HFD mice proved that IAA and KYNA could reproduce the effects of QA that suppress brain oxidative stress and inflammation and decrease the levels of of Aβ and p-Tau. Transcriptomics analysis of brain after IAA administration revealed the inhibition of DR3/IKK/NF-κB signaling pathway by IAA. In conclusion, this study demonstrated that QA could counteract HFD-induced brain oxidative stress and neuroinflammation by regulating inflammatory DR3/IKK/NF-κB signaling pathway via gut microbial tryptophan metabolites.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2374608"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11229714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554714","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":"Phage lysins for intestinal microbiome modulation: current challenges and enabling techniques.","authors":"Iris Pottie, Roberto Vázquez Fernández, Tom Van de Wiele, Yves Briers","doi":"10.1080/19490976.2024.2387144","DOIUrl":"10.1080/19490976.2024.2387144","url":null,"abstract":"<p><p>The importance of the microbiota in the intestinal tract for human health has been increasingly recognized. In this perspective, microbiome modulation, a targeted alteration of the microbial composition, has gained interest. Phage lysins, peptidoglycan-degrading enzymes encoded by bacteriophages, are a promising new class of antibiotics currently under clinical development for treating bacterial infections. Due to their high specificity, lysins are considered microbiome-friendly. This review explores the opportunities and challenges of using lysins as microbiome modulators. First, the high specificity of endolysins, which can be further modulated using protein engineering or targeted delivery methods, is discussed. Next, obstacles and possible solutions to assess the microbiome-friendliness of lysins are considered. Finally, lysin delivery to the intestinal tract is discussed, including possible delivery methods such as particle-based and probiotic vehicles. Mapping the hurdles to developing lysins as microbiome modulators and identifying possible ways to overcome these hurdles can help in their development. In this way, the application of these innovative antimicrobial agents can be expanded, thereby taking full advantage of their characteristics.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2387144"},"PeriodicalIF":12.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897312","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":"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}

{"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}

{"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}