{"title":"3'-Sialyllactose and <i>B. infantis</i> synergistically alleviate gut inflammation and barrier dysfunction by enriching cross-feeding bacteria for short-chain fatty acid biosynthesis.","authors":"Mingzhi Yang, Zipeng Jiang, Lutong Zhou, Nana Chen, Huan He, Wentao Li, Zhixin Yu, Siming Jiao, Deguang Song, Yizhen Wang, Mingliang Jin, Zeqing Lu","doi":"10.1080/19490976.2025.2486512","DOIUrl":"10.1080/19490976.2025.2486512","url":null,"abstract":"<p><p>Ulcerative colitis (UC) poses significant threats to human health and quality of life worldwide, as it is a chronic inflammatory bowel disease. 3'-sialyllactose (3'-SL) is a key functional component of milk oligosaccharides. This study systematically evaluates the prebiotic effects of 3'-SL and its therapeutic potential in combination with <i>Bifidobacterium infantis</i> (<i>B. infantis</i>) for UC. The findings reveal that 3'-SL and <i>B. infantis</i> synergistically mitigate intestinal inflammation and barrier dysfunction by promoting the production of short-chain fatty acids (SCFAs) through cross-feeding mechanisms among gut microbiota. Individually, 3'-SL, <i>B. infantis</i>, and the synbiotic treatment all effectively alleviated UC symptoms, including reduced weight loss, improved disease activity scores, and prevention of colon shortening. Histopathological and immunofluorescence analyses further demonstrated that the synbiotic treatment significantly ameliorated colonic injury, enhanced barrier function, restored goblet cell counts, increased glycoprotein content in crypt goblet cells, and upregulated the expression of tight junction proteins (ZO-1, occludin, and claudin-1). Notably, the synbiotic treatment outperformed the individual components by better restoring gut microbiota balance, elevating SCFA levels, and modulating serum cytokine profiles, thereby reducing inflammation. These findings provide mechanistic insights into the protective effects of the synbiotic and underscore its therapeutic potential for UC and other intestinal inflammatory disorders.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2486512"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11988227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803220","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":"Deep learning-based detection of bacterial swarm motion using a single image.","authors":"Yuzhu Li, Hao Li, Weijie Chen, Keelan O'Riordan, Neha Mani, Yuxuan Qi, Tairan Liu, Sridhar Mani, Aydogan Ozcan","doi":"10.1080/19490976.2025.2505115","DOIUrl":"10.1080/19490976.2025.2505115","url":null,"abstract":"<p><p>Motility is a fundamental characteristic of bacteria. Distinguishing between swarming and swimming, the two principal forms of bacterial movement, holds significant conceptual and clinical relevance. Conventionally, the detection of bacterial swarming involves inoculating samples on an agar surface and observing colony expansion, which is qualitative, time-intensive, and requires additional testing to rule out other motility forms. A recent methodology that differentiates swarming and swimming motility in bacteria using circular confinement offers a rapid approach to detecting swarming. However, it still heavily depends on the observer's expertise, making the process labor-intensive, costly, slow, and susceptible to inevitable human bias. To address these limitations, we developed a deep learning-based swarming classifier that rapidly and autonomously predicts swarming probability using a single blurry image. Compared with traditional video-based, manually processed approaches, our method is particularly suited for high-throughput environments and provides objective, quantitative assessments of swarming probability. The swarming classifier demonstrated in our work was trained on <i>Enterobacter sp</i>. SM3 and showed good performance when blindly tested on new swarming (positive) and swimming (negative) test images of SM3, achieving a sensitivity of 97.44% and a specificity of 100%. Furthermore, this classifier demonstrated robust external generalization capabilities when applied to unseen bacterial species, such as <i>Serratia marcescens</i> DB10 and <i>Citrobacter koseri</i> H6. This competitive performance indicates the potential to adapt our approach for diagnostic applications through portable devices, which would facilitate rapid, objective, on-site screening for bacterial swarming motility, potentially enhancing the early detection and treatment assessment of various diseases, including inflammatory bowel diseases (IBD) and urinary tract infections (UTI).</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2505115"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077484","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 : 2025-12-01Epub Date: 2025-06-05DOI: 10.1080/19490976.2025.2515480
Amandine Devaux, Romain Villéger, Gwenaëlle Roche, Binta Diémé, Michael Rodrigues, Charline Juban, Marie Lagrée, Nicolas Venisse, Cyril Jousse, Nicolas Barnich, Mathilde Bonnet
{"title":"L-serine promotes pro-carcinogenic effects of colibactin-producing <i>E. coli</i>.","authors":"Amandine Devaux, Romain Villéger, Gwenaëlle Roche, Binta Diémé, Michael Rodrigues, Charline Juban, Marie Lagrée, Nicolas Venisse, Cyril Jousse, Nicolas Barnich, Mathilde Bonnet","doi":"10.1080/19490976.2025.2515480","DOIUrl":"10.1080/19490976.2025.2515480","url":null,"abstract":"<p><p>Colonic tissues are abnormally colonized by colibactin-producing <i>Escherichia coli</i> (CoPEC) in colorectal cancer (CRC) patients. CoPECs have been shown to promote colorectal carcinogenesis in several pre-clinical CRC mouse models. Here, we report that CoPEC reprograms the metabolism of colonic epithelial cells in a colibactin-dependent manner, leading to a Warburg-like effect, altered redox homeostasis, and disrupted amino acid metabolism. Among these metabolic modifications, we observed a significant decrease in both extracellular and intracellular serine levels. We found that CoPEC activates the L-serine-utilization operon during gut colonization, maximizing its competitive fitness advantage over a commensal strain. Moreover, an L-serine-depleted diet induces an early and transient decrease in CoPEC colonization of mice gut, associated with decrease of both DNA damages and tumor development. Finally, deletion of the bacterial <i>tdcA</i> gene involved in L-serine operon utilization reduces the competitive fitness of CoPEC, the <i>in vitro</i> adhesion and persistence within the epithelial cells and leads in CRC animal models to reduced carcinogenic activity of the pathobiont. This work highlights the interplay between intestinal microbiota factors, such as CoPEC, and nutritional factors, such as L-serine, in colorectal carcinogenesis.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2515480"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225314","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 : 2025-12-01Epub Date: 2025-06-09DOI: 10.1080/19490976.2025.2512016
Meriem Boukili, Omar Zmerli, Florence Fenollar, Sara Bellali, Jacques Bou Khalil
{"title":"Tips and tricks for gut microbiota investigation using scanning electron microscopy (SEM): going from sample preparation to imaging and landscape analysis.","authors":"Meriem Boukili, Omar Zmerli, Florence Fenollar, Sara Bellali, Jacques Bou Khalil","doi":"10.1080/19490976.2025.2512016","DOIUrl":"10.1080/19490976.2025.2512016","url":null,"abstract":"<p><p>The Gut Microbiota (GM) remains a complex microbial ecosystem with many unknown facets despite significant technologic advancement. This study introduces a novel rapid technique using tabletop scanning electron microscopy (SEM) for investigating GM composition, focusing on <i>Clostridioides difficile</i> infection (CDI) as a representative model for dysbiosis-related diseases. Six stool sample preparation protocols were tested on 40 stool samples to develop an optimized SEM protocol. Protocol stability was evaluated after four-month storage. The optimized protocol produced high-resolution micrographs while maintaining sample integrity over time. SEM investigation of GM was done by analyzing ten stool samples (5-control and 5-<i>C. difficile</i> groups), imaged at low and high magnifications. Object detection analysis generated a SEM-based GM components database helping describe and compare microbial diversity variation between the groups. CDI group revealed a reduction in microbial diversity, compared to the controls. Epithelial and red blood cells were more prevalent in CDI group. Statistical analyses of objects proved clear clustering of samples into CDI and control groups. This study pioneers the proof-of-concept for using tabletop SEM to investigate GM components in a dysbiosis-related disease model. This concept emerges as a complementary technique capable of providing deeper insight to describe GM components previously elusive with other methods.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2512016"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257967","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 : 2025-12-01Epub Date: 2025-06-12DOI: 10.1080/19490976.2025.2517377
Moshe Maor, Hilit Levy Barazany, Ilana Kolodkin-Gal
{"title":"The ladder of regulatory stringency and balance: an application to the US FDA's regulation of bacterial live therapeutics.","authors":"Moshe Maor, Hilit Levy Barazany, Ilana Kolodkin-Gal","doi":"10.1080/19490976.2025.2517377","DOIUrl":"10.1080/19490976.2025.2517377","url":null,"abstract":"<p><p>The three main types of live bacterial therapies - probiotics, fecal/microbiome transplants, and engineered bacterial therapies - hold immense potential to revolutionize medicine. While offering targeted and personalized treatments for various diseases, these therapies also carry risks such as adverse immune reactions, antibiotic resistance, and the potential for unintended consequences. Therefore, developing and deploying these therapies necessitates a robust regulatory framework to protect public health while fostering innovation. In this paper, we propose a novel conceptual tool - the <i>Ladder of Regulatory Stringency and Balance</i>-which can assist in the design of robust regulatory regimes which encompass medicine practices based not only on definitive Randomized Controlled Trials (RCTs), but also on meta-analyses, observational studies, and clinicians experience. Regulatory stringency refers to the strictness of regulations, while regulatory balance concerns the degree of alignment between the regulatory framework governing a technology and the actual risks posed by specific products within that technology. Focusing on the US regulatory environment, we subsequently position the three types of live bacterial therapies on the <i>Ladder</i>. The insight gained from this exercise demonstrates that probiotics are generally positioned at the bottom of the <i>Ladder</i>, corresponding to low-stringency regulation, with a proportionate regulatory balance. However, probiotics intended for high-risk populations are currently subject to low-stringency regulations, resulting in under-regulation. Our analysis also supports the conclusion that fecal microbiota transplants (FMT) for recurrent <i>Clostridium difficile</i> infection should be positioned close to but below the threshold for under regulation by the U.S. Food and Drug Administration (FDA), and we recommend improved donor screening procedures, preservation and processing, storage, and distribution. Our framework can serve as a scale to assess regulatory gaps for live bacterial therapies and to identify potential solutions where such gaps exist.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2517377"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274742","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 : 2025-12-01Epub Date: 2025-06-12DOI: 10.1080/19490976.2025.2517828
Eva Vermeer, Jasmijn Z Jagt, Eline M Lap, Eduard A Struys, Andries E Budding, Nanda M Verhoeven-Duif, Marjolein Bosma, Johan E van Limbergen, Bart G P Koot, Robert de Jonge, Marc A Benninga, Animesh Acharjee, Nanne K H de Boer, Tim G J de Meij
{"title":"Fecal gut microbiota and amino acids as noninvasive diagnostic biomarkers of Pediatric inflammatory bowel disease.","authors":"Eva Vermeer, Jasmijn Z Jagt, Eline M Lap, Eduard A Struys, Andries E Budding, Nanda M Verhoeven-Duif, Marjolein Bosma, Johan E van Limbergen, Bart G P Koot, Robert de Jonge, Marc A Benninga, Animesh Acharjee, Nanne K H de Boer, Tim G J de Meij","doi":"10.1080/19490976.2025.2517828","DOIUrl":"10.1080/19490976.2025.2517828","url":null,"abstract":"<p><strong>Background and aims: </strong>Fecal calprotectin (FCP) has limited specificity as diagnostic biomarker of pediatric inflammatory bowel disease (IBD), leading to unnecessary invasive endoscopies. This study aimed to develop and validate a fecal microbiota and amino acid (AA)-based diagnostic model.</p><p><strong>Methods: </strong>Fecal samples from a discovery cohort (<i>de novo</i> IBD and healthy controls [HC]) were used to develop the diagnostic model. This model was applied in a validation cohort (<i>de novo</i> IBD and controls with gastrointestinal symptoms [CGI]). Microbiota and AAs were analyzed using interspace profiling and liquid chromatography-mass spectrometry techniques, respectively. Machine learning techniques were used to build the diagnostic model.</p><p><strong>Results: </strong>In the discovery cohort (58 IBD, 59 hC), two microbial species (<i>Escherichia coli</i> and <i>Alistipes finegoldii</i>) and four AAs (leucine, ornithine, taurine, and alpha-aminoadipic acid [AAD]) combined allowed for discrimination between both subgroups (AUC 0.94, 95% CI [0.89, 0.98]). In the validation cohort (43 IBD, 38 CGI), this panel of six markers could differentiate patients with IBD from CGI with an AUC of 0.84, 95% CI [0.67, 0.95]). Leucine showed the best diagnostic performance (AUC 0.89, 95% CI [0.81, 0.95]).</p><p><strong>Conclusions: </strong>Leucine might serve as adjuvant noninvasive biomarker in the diagnostic work-up of pediatric IBD. Future research should investigate whether the combination of leucine with FCP could improve specificity and may help tailor the course of diagnostics.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2517828"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12164387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274741","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 : 2025-12-01Epub Date: 2025-03-18DOI: 10.1080/19490976.2025.2479772
Monica A Batalha, Madison N LeCroy, Juan Lin, Brandilyn A Peters, Qibin Qi, Zheng Wang, Tao Wang, Linda C Gallo, Gregory A Talavera, Amanda C McClain, Bharat Thyagarajan, Martha L Daviglus, Lifang Hou, Maria Llabre, Jianwen Cai, Robert C Kaplan, Carmen R Isasi
{"title":"Life-course socioeconomic position and the gut microbiome in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).","authors":"Monica A Batalha, Madison N LeCroy, Juan Lin, Brandilyn A Peters, Qibin Qi, Zheng Wang, Tao Wang, Linda C Gallo, Gregory A Talavera, Amanda C McClain, Bharat Thyagarajan, Martha L Daviglus, Lifang Hou, Maria Llabre, Jianwen Cai, Robert C Kaplan, Carmen R Isasi","doi":"10.1080/19490976.2025.2479772","DOIUrl":"10.1080/19490976.2025.2479772","url":null,"abstract":"<p><p>Socioeconomic position (SEP) in childhood and beyond may influence the gut microbiome, with implications for disease risk. Studies evaluating the relationship between life-course SEP and the gut microbiome are sparse, particularly among Hispanic/Latino individuals, who have a high prevalence of low SEP. We use the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a population-based cohort study conducted in four field centers in the United States (U.S.), to evaluate the association between life-course SEP and gut microbiome composition. Life-course SEP indicators included parental education (proxy of childhood SEP), current SEP (<i>n</i> = 2174), and childhood (<i>n</i> = 988) and current economic hardship (<i>n</i> = 994). Shotgun sequencing was performed on stool samples. Analysis of Compositions of Microbiomes was used to identify associations of life-course SEP indicators with gut microbiome species and functions. Parental education and current SEP were associated with the overall gut microbiome composition; however, parental education and current education explained more the gut microbiome variance than the current SEP. A lower parental education and current SEP were associated with a lower abundance of species from genus <i>Bacteroides</i>. In stratified analysis by nativity, we found similar findings mainly among foreign-born participants. Early-life SEP may have long-term effects on gut microbiome composition underscoring another biological mechanism linking early childhood factors to adult disease.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2479772"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657019","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 : 2025-12-01Epub Date: 2025-08-19DOI: 10.1080/19490976.2025.2543123
Pollyana Ribeiro Castro, Renan Oliveira Corrêa, Monara Kaélle Sérvulo Cruz Angelim, Vinícius de Rezende Rodovalho, Mariane Font Fernandes, Vinícius Dias Nirello, Arilson Bernardo Dos Santos Pereira Gomes, Jaqueline de Souza Felipe, Lais Passarielo Pral, Sarah de Oliveira, Patrícia Brito Rodrigues, José Luís Fachi, Guilherme Reis-de-Oliveira, Bradley J Smith, Victor C Carregari, Nicolas G Shealy, Catherine Shelton, Daniel Martins-de-Souza, Pedro M Moraes-Vieira, Mariana Xavier Byndloss, Patrick Varga-Weisz, Marco Aurélio Ramirez Vinolo
{"title":"HIF-1 attenuates high-fiber diet-mediated proliferation and stemness of colonic epithelium.","authors":"Pollyana Ribeiro Castro, Renan Oliveira Corrêa, Monara Kaélle Sérvulo Cruz Angelim, Vinícius de Rezende Rodovalho, Mariane Font Fernandes, Vinícius Dias Nirello, Arilson Bernardo Dos Santos Pereira Gomes, Jaqueline de Souza Felipe, Lais Passarielo Pral, Sarah de Oliveira, Patrícia Brito Rodrigues, José Luís Fachi, Guilherme Reis-de-Oliveira, Bradley J Smith, Victor C Carregari, Nicolas G Shealy, Catherine Shelton, Daniel Martins-de-Souza, Pedro M Moraes-Vieira, Mariana Xavier Byndloss, Patrick Varga-Weisz, Marco Aurélio Ramirez Vinolo","doi":"10.1080/19490976.2025.2543123","DOIUrl":"10.1080/19490976.2025.2543123","url":null,"abstract":"<p><p>The complex interplay between diet, microbiota, and host is exemplified by the effects of dietary fiber on the intestine. Inulin ingestion triggers epithelial changes in the colon that depend on microbiota-derived molecules, including enhanced proliferation, increased mucus production, and elevated antimicrobial peptide secretion. Here we employed a multilayered and multi-omics approach, including dietary interventions, intestinal organoids, and both genetic and pharmacological interventions to investigate the impact of inulin on two aspects of diet-microbiota-host interactions: intestinal hypoxia and hypoxia-inducible factor (HIF)-1 signaling in intestinal epithelial cells (IECs). We found that inulin, a soluble fiber, promotes intestinal hypoxia, stabilizing HIF-1 in IECs in a microbiota- and host-dependent manner. Furthermore, we show that HIF-1 stabilization modulates intestinal stem cell (ISC) function through metabolic reprogramming in a microbiota-dependent manner. Our findings reveal an unrecognized role for HIF-1 in orchestrating microbiota-dependent epithelial metabolism and proliferation in the colon, underscoring the complexity of diet-microbiota-host interactions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2543123"},"PeriodicalIF":11.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144872880","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 : 2025-12-01Epub Date: 2025-01-06DOI: 10.1080/19490976.2024.2446375
Chrissa Petersen, Adhini Kuppuswamy Satheesh Babu, Ceres Mattos Della Lucia, Henry A Paz, Lisard Iglesias-Carres, Ying Zhong, Thunder Jalili, J David Symons, Kartik Shankar, Andrew P Neilson, Umesh D Wankhade, Pon Velayutham Anandh Babu
{"title":"Gut microbes metabolize strawberry phytochemicals and mediate their beneficial effects on vascular inflammation.","authors":"Chrissa Petersen, Adhini Kuppuswamy Satheesh Babu, Ceres Mattos Della Lucia, Henry A Paz, Lisard Iglesias-Carres, Ying Zhong, Thunder Jalili, J David Symons, Kartik Shankar, Andrew P Neilson, Umesh D Wankhade, Pon Velayutham Anandh Babu","doi":"10.1080/19490976.2024.2446375","DOIUrl":"https://doi.org/10.1080/19490976.2024.2446375","url":null,"abstract":"<p><p>Evidence suggests that a healthy gut microbiome is essential for metabolizing dietary phytochemicals. However, the microbiome's role in metabolite production and the influence of gut dysbiosis on this process remain unclear. Further, studies on the relationship among gut microbes, metabolites, and biological activities of phytochemicals are limited. We addressed this knowledge gap using strawberry phytochemicals as a model. C57BL/6J mice were fed a standard diet [C]; strawberry-supplemented diet (~2 human servings) [CS]; strawberry-supplemented diet and treated with antibiotics (to deplete gut microbes) [CSA]; high-fat diet (HFD) [HF]; strawberry-supplemented HFD [HS]; and strawberry-supplemented HFD and treated with antibiotics [HSA] for 12 weeks. First, antibiotic treatment suppressed the production of selected metabolites (CSA <i>vs</i>. CS), and <i>p</i>-coumaric acid was identified as a strawberry-derived microbial metabolite. Second, HFD-induced dysbiosis negatively affected metabolite production (HS <i>vs</i>. HF), and hippuric acid was identified as a microbial metabolite in HFD conditions. Third, dietary strawberries improved HFD-induced vascular inflammation (HS <i>vs</i>. HF). However, antibiotic treatment reduced metabolite production and abolished the vascular effects of strawberries (HSA <i>vs</i>. HS), indicating the importance of gut microbes in mediating the vascular benefits of strawberries <i>via</i> metabolites. Fourth, strawberry supplementation decreased <i>Coprobacillus</i> that was positively associated with vascular inflammation, whereas it increased <i>Lachnospiraceae</i> that was negatively associated with vascular inflammation and positively associated with hippuric acid. Fifth, hippuric acid was negatively associated with vascular inflammation. Our study fills in some pieces of the giant puzzle regarding the influence of gut microbes on the biological activities of phytochemicals. HFD-induced gut dysbiosis negatively impacts metabolite production and a strong association exists among gut microbes, strawberry-derived microbial metabolites, and the vascular benefits of dietary strawberries. Further, our study provides significant proof of concept to warrant future research on the use of strawberries as a nutritional strategy to prevent vascular complications.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2446375"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931580","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 : 2025-12-01Epub Date: 2024-12-24DOI: 10.1080/19490976.2024.2444411
Jazmin Meza-Torres, Jean-Yves Tinevez, Aline Crouzols, Héloïse Mary, Minhee Kim, Lise Hunault, Susan Chamorro-Rodriguez, Emilie Lejal, Pamela Altamirano-Silva, Déborah Groussard, Samy Gobaa, Johann Peltier, Benoit Chassaing, Bruno Dupuy
{"title":"<i>Clostridioides difficile</i> binary toxin CDT induces biofilm-like persisting microcolonies.","authors":"Jazmin Meza-Torres, Jean-Yves Tinevez, Aline Crouzols, Héloïse Mary, Minhee Kim, Lise Hunault, Susan Chamorro-Rodriguez, Emilie Lejal, Pamela Altamirano-Silva, Déborah Groussard, Samy Gobaa, Johann Peltier, Benoit Chassaing, Bruno Dupuy","doi":"10.1080/19490976.2024.2444411","DOIUrl":"https://doi.org/10.1080/19490976.2024.2444411","url":null,"abstract":"<p><p>Clinical symptoms of <i>Clostridioides difficile</i> infection (CDI) range from diarrhea to pseudomembranous colitis. A major challenge in managing CDI is the high rate of relapse. Several studies correlate the production of CDT binary toxin by clinical strains of <i>C. difficile</i> with higher relapse rates. Although the mechanism of action of CDT on host cells is known, its exact contribution to CDI is still unclear. To understand the physiological role of CDT during CDI, we established two hypoxic relevant intestinal models, Transwell and Microfluidic Intestine-on-Chip systems. Both were challenged with the epidemic strain UK1 CDT<sup>+</sup> and its isogenic CDT<sup>-</sup> mutant. We report that CDT induces mucin-associated microcolonies that increase <i>C. difficile</i> colonization and display biofilm-like properties by enhancing <i>C. difficile</i> resistance to vancomycin. Importantly, biofilm-like microcolonies were also observed in the cecum and colon of infected mice. Hence, our study shows that CDT induces biofilm-like microcolonies, increasing <i>C. difficile</i> persistence and risk of relapse.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2444411"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885583","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}