Gut Microbes最新文献

{"title":"Engineering non-pathogenic bacteria for auto-transporter-driven secretion of functional interferon.","authors":"May Tfilin Samuel, Irina Rostovsky, Alona Kuzmina, Ran Taube, Neta Sal-Man","doi":"10.1080/19490976.2025.2474146","DOIUrl":"10.1080/19490976.2025.2474146","url":null,"abstract":"<p><p>In recent years, various strategies have been developed to enable the oral administration of protein-based drugs (biologics) with the aim of overcoming the degradation and inactivation of these drugs that can occur as they traverse the gastrointestinal tract (GIT). In this study, we investigated bacteria as a delivery vehicle for biologics, harnessing their ability to withstand the harsh gastric environment and deliver therapeutic drugs directly to the intestine. Specifically, we explored using the type 5 secretion system (T5SS) to secrete therapeutic cargoes under simulated gut conditions. Our research focused on EspC, a T5SS protein from enteropathogenic <i>Escherichia coli</i>, and its potential to secrete interferon-α (IFNα), a cytokine with immunomodulatory and antiviral properties widely used in the clinic. We demonstrated that EspC can facilitate the secretion of IFNα variant when expressed in nonpathogenic bacteria. Moreover, this EspC-secreted IFN was able to activate the JAK-STAT pathway, upregulate IFN-stimulated genes, and induce a robust antiviral response in cells. Collectively, these findings provide proof of concept supporting the utilization of the EspC protein as a novel delivery platform for protein-based therapeutics.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2474146"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541426","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":"Microbiota transplant therapy in inflammatory bowel disease: advances and mechanistic insights.","authors":"Daphne Moutsoglou, Pavithra Ramakrishnan, Byron P Vaughn","doi":"10.1080/19490976.2025.2477255","DOIUrl":"10.1080/19490976.2025.2477255","url":null,"abstract":"<p><p>Microbiota transplant therapy is an emerging therapy for inflammatory bowel disease, but factors influencing its efficacy and mechanism remain poorly understood. In this narrative review, we outline key elements affecting therapeutic outcomes, including donor factors (such as age and patient relationship), recipient factors, control selection, and elements impacting engraftment and its correlation with clinical response. We also examine potential mechanisms through inflammatory bowel disease trials, focusing on the interplay between the microbiota, host, and immune system. Finally, we briefly explore potential future directions for microbiota transplant therapy and promising emerging treatments.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2477255"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585382","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":"Profiling the gut microbiota to assess infection risk in <i>Klebsiella pneumoniae</i>-colonized patients.","authors":"Flavio De Maio, Delia Mercedes Bianco, Giulia Santarelli, Roberto Rosato, Francesca Romana Monzo, Barbara Fiori, Maurizio Sanguinetti, Brunella Posteraro","doi":"10.1080/19490976.2025.2468358","DOIUrl":"10.1080/19490976.2025.2468358","url":null,"abstract":"<p><p>Vornhagen et al. introduced a model combining gut microbiota structure and <i>Klebsiella pneumoniae</i> genotype to assess infection risk in <i>K. pneumoniae</i>-colonized patients. Building on their findings, we investigated the gut microbiota composition and <i>K. pneumoniae</i> genotype in 16 colonized patients, five of whom had bloodstream infections at the time of fecal sampling. Importantly, we did not apply the original machine learning model due to the small sample size of our cohort. Instead, we explored the distribution of key antimicrobial resistance and stress resistance genes and analyzed gut community structure based on amplicon sequence variants (ASVs) of the V3-V4 16S rRNA region. Notably, distinct gene profiles were observed in both infected and non-infected patients, and three patients without bloodstream infections showed no detectable <i>Klebsiella</i> ASVs despite microbiological confirmation of colonization. These findings highlight the need to integrate gut microbiota composition data into infection risk assessment and address limitations in taxonomic resolution and sample size. Future studies should aim to develop streamlined tools for clinical application in <i>K. pneumoniae</i>-colonized patients.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2468358"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440726","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":"Interbacterial warfare in the human gut: insights from Bacteroidales' perspective.","authors":"Kun Jiang, Xinxin Pang, Weixun Li, Xiaoning Xu, Yan Yang, Chengbin Shang, Xiang Gao","doi":"10.1080/19490976.2025.2473522","DOIUrl":"10.1080/19490976.2025.2473522","url":null,"abstract":"<p><p>Competition and cooperation are fundamental to the stability and evolution of ecological communities. The human gut microbiota, a dense and complex microbial ecosystem, plays a critical role in the host's health and disease, with competitive interactions being particularly significant. As a dominant and extensively studied group in the human gut, Bacteroidales serves as a successful model system for understanding these intricate dynamic processes. This review summarizes recent advances in our understanding of the intricate antagonism mechanisms among gut Bacteroidales at the biochemical or molecular-genetic levels, focusing on interference and exploitation competition. We also discuss unresolved questions and suggest strategies for studying the competitive mechanisms of Bacteroidales. The review presented here offers valuable insights into the molecular basis of bacterial antagonism in the human gut and may inform strategies for manipulating the microbiome to benefit human health.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2473522"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556597","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 extracellular vesicles in the initiation, progression and treatment of atherosclerosis.","authors":"Yuling Lin, Jingyu Wang, Fan Bu, Ruyi Zhang, Junhui Wang, Yubing Wang, Mei Huang, Yiyi Huang, Lei Zheng, Qian Wang, Xiumei Hu","doi":"10.1080/19490976.2025.2452229","DOIUrl":"10.1080/19490976.2025.2452229","url":null,"abstract":"<p><p>Atherosclerosis is the primary cause of cardiovascular and cerebrovascular diseases. However, current anti-atherosclerosis drugs have shown conflicting therapeutic outcomes, thereby spurring the search for novel and effective treatments. Recent research indicates the crucial involvement of oral and gastrointestinal microbiota in atherosclerosis. While gut microbiota metabolites, such as choline derivatives, have been extensively studied and reviewed, emerging evidence suggests that bacterial extracellular vesicles (BEVs), which are membrane-derived lipid bilayers secreted by bacteria, also play a significant role in this process. However, the role of BEVs in host-microbiota interactions remains insufficiently explored. This review aims to elucidate the complex communication mediated by BEVs along the gut-heart axis. In this review, we summarize current knowledge on BEVs, with a specific focus on how pathogen-derived BEVs contribute to the promotion of atherosclerosis, as well as how BEVs from gut symbionts and probiotics may mitigate its progression. We also explore the potential and challenges associated with engineered BEVs in the prevention and treatment of atherosclerosis. Finally, we discuss the benefits and challenges of using BEVs in atherosclerosis diagnosis and treatment, and propose future research directions to address these issues.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2452229"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004537","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}

{"title":"Novel role of FTO in regulation of gut-brain communication via <i>Desulfovibrio fairfieldensis</i>-produced hydrogen sulfide under arsenic exposure.","authors":"Ruonan Chen, Xiaoqin Chai, Yunxiao Zhang, Tianxiu Zhou, Yinyin Xia, Xuejun Jiang, Bo Lv, Jun Zhang, Lixiao Zhou, Xin Tian, Ruonan Wang, Lejiao Mao, Feng Zhao, Hongyang Zhang, Jun Hu, Jingfu Qiu, Zhen Zou, Chengzhi Chen","doi":"10.1080/19490976.2024.2438471","DOIUrl":"10.1080/19490976.2024.2438471","url":null,"abstract":"<p><p>Fat mass and obesity-associated protein (FTO) is the key demethylase that reverses the abnormally altered N6-methyladenosine (m6A) modification in eukaryotic cells under environmental pollutants exposure. Arsenic is an environmental metalloid and can cause severe symptoms in human mainly through drinking water. However, there is no specific treatment for its toxic effects due to the uncovered mechanisms. We previously revealed that exposure to arsenic increased the level of m6A via down-regulation of FTO, which might serve as a potential target for intervention against arsenic-related disorders. In this study, our results demonstrated that chronic exposure to arsenic significantly disrupted the intestinal barrier and microenvironment. Also, this administration resulted in the enhancement of m6A modification and the reduction of FTO expression in the intestine. By using both CRISPR/Cas9-based FTO knock-in strategy and adeno-associated virus (AAV)-mediated overexpression of FTO in the intestine, we established for the first time that up-regulation of FTO remarkably ameliorated arsenic-induced disruption of intestinal barriers and altered microenvironment of mice. We also firstly identified a dominant gut microbial species, <i>Desulfovibrio fairfieldensis</i>, which was sharply reduced in arsenic-exposed mice, was able to proceed arsenic-induced neurobehavioral impairments by declining the levels of its major metabolite hydrogen sulfide. Administration of <i>Desulfovibrio fairfieldensis</i> could significantly alleviate the neurotoxicity of arsenic. Intriguingly, the beneficial effects of FTO against arsenic neurotoxicity possibly occurred through a novel gut-brain communication via <i>Desulfovibrio fairfieldensis</i> and its produced hydrogen sulfide. Collectively, these findings will provide new ideas for understanding the mechanisms of arsenic-induced toxic effects from a gut-brain communication perspective, and will assist the development of explicit intervention strategy via regulation of a new potential target FTO for prevention and treatment against arsenic-related both intestinal and neurological disorders.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2438471"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033093","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":"Anxiety-like behavior during protracted morphine withdrawal is driven by gut microbial dysbiosis and attenuated with probiotic treatment.","authors":"Mark Oppenheimer, Junyi Tao, Shamsudheen Moidunny, Sabita Roy","doi":"10.1080/19490976.2025.2517838","DOIUrl":"10.1080/19490976.2025.2517838","url":null,"abstract":"<p><p>The development of anxiety during protracted opioid withdrawal heightens the risk of relapse into the cycle of addiction. Understanding the mechanisms driving anxiety during opioid withdrawal could facilitate the development of therapeutics to prevent negative affect and promote continued abstinence. Our lab has previously established the gut microbiome as a driver of various side effects of opioid use, including analgesic tolerance and somatic withdrawal symptoms. We therefore hypothesized that the gut microbiome contributes to the development of anxiety-like behavior during protracted opioid withdrawal. In this study, we first established a mouse model of protracted morphine withdrawal, characterized by anxiety-like behavior and gut microbial dysbiosis. Next, we used fecal microbiota transplantation (FMT) to show that gut dysbiosis alone is sufficient to induce anxiety-like behavior. We further demonstrated that probiotic therapy during morphine withdrawal attenuated the onset of anxiety-like behavior, highlighting its therapeutic potential. Lastly, we examined transcriptional changes in the amygdala of morphine-withdrawn mice treated with probiotics to explore mechanisms by which the gut-brain axis mediates anxiety-like behavior. Our results support the use of probiotics as a promising therapeutic strategy to prevent gut dysbiosis and associated anxiety during opioid withdrawal, with potential implications for improving treatment outcomes in opioid recovery programs.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2517838"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301922","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":"Lactulose selectively stimulates members of the gut microbiota, as determined by multi-modal activity-based sorting.","authors":"Hamid Rasoulimehrabani, Alessandra Riva, Deniz Inan, Adnan Hodžić, Bela Hausmann, Georgi Nikolov, Sanaz Khadem, Norbert Hieger, Julia Wiesenbauer, Christina Kaiser, Verena Filz, Thomas Böttcher, David Berry","doi":"10.1080/19490976.2025.2525482","DOIUrl":"https://doi.org/10.1080/19490976.2025.2525482","url":null,"abstract":"<p><p>There is much interest in the development of dietary supplements that selectively promote the growth of beneficial gut bacteria. The selectivity of many candidate prebiotics has, however, not been thoroughly investigated. Here, we evaluated stimulation of the human gut microbiota by the disaccharide lactulose using an <i>ex vivo</i> multimodal activity-based cell sorting approach. Incubation of human donor stool with lactulose resulted in growth or stimulation of a restricted diversity of bacterial genera, most prominently <i>Bifidobacterium</i>, <i>Collinsella</i>, and <i>Lactococcus</i>. Physiological analysis of lactulose-responsive strains isolated by Raman activated cell sorting revealed that most were capable of lactulose degradation. Among these isolates, <i>Lactococcus lactis</i> could not degrade lactulose, but its growth was boosted by co-cultivation with lactulose degraders. This suggests that inter-species facilitation contributes to the lactulose degradation niche. Moreover, we observed that lactulose selectively activates metabolically important taxa, including health-associated genera such as <i>Faecalibacterium</i> and <i>Gemmiger</i>^1,2,3, potentially indicating broader functional effects beyond compositional changes. These results provide novel insights into the physiology and ecology of lactulose utilization by the human gut microbiota and underscore the potential of lactulose as a prebiotic dietary supplement.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2525482"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505551","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}

{"title":"Implications of gut microbiota-mediated epigenetic modifications in intestinal diseases.","authors":"Qihong Zhang, Yun Liu, Yuheng Li, Guangdong Bai, Jiaman Pang, Miaomiao Wu, Jiawei Li, Xuan Zhao, Yaoyao Xia","doi":"10.1080/19490976.2025.2508426","DOIUrl":"10.1080/19490976.2025.2508426","url":null,"abstract":"<p><p>Intestinal diseases are highly prevalent, affecting millions worldwide and significantly contributing to global morbidity. The treatment of complex disorders, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), remains challenging due to multifactorial etiologies, diverse patient responses, and the limitations of current therapeutic strategies. Although the gut microbiota clearly plays a role in regulating the onset of intestinal diseases, few studies have explored the epigenetic factors by which the microbiota contributes to disease development. Here, the latest insights into the molecular mechanisms underlying the bidirectional influence between gut microbiota and epigenetic modifications are discussed, including DNA methylation, histone modifications, non-coding RNAs, and <i>N</i>6-methyladenosine (m⁶A). Importantly, mechanistic studies based on animal models or human cells have demonstrated that the gut microbiota, and other environmental factors, influence targeted gene expression and activate immune pathways through host epigenetic dysregulation, which are closely associated with the development of IBD and CRC. Furthermore, potential microbiome interventions, including probiotics, prebiotics and postbiotics, fecal microbiota transplantation (FMT), dietary modifications, and phage therapy, have been proposed as innovative therapeutic strategies to correct these abnormal epigenetic patterns associated with the diseases. Overall, addressing microbiome dysbiosis and its epigenetic consequences presents a promising frontier in the treatment of intestinal diseases, offering the potential to not only restore microbial balance but also provide more targeted and personalized therapeutic strategies for better patient outcomes.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2508426"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215671","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 bacteriophages on gut microbiome functionality.","authors":"Elena Kurilovich, Naama Geva-Zatorsky","doi":"10.1080/19490976.2025.2481178","DOIUrl":"10.1080/19490976.2025.2481178","url":null,"abstract":"<p><p>The gut microbiome, composed of bacteria, fungi, and viruses, plays a crucial role in maintaining the delicate balance of human health. Emerging evidence suggests that microbiome disruptions can have far-reaching implications, ranging from the development of inflammatory diseases and cancer to metabolic disorders. Bacteriophages, or \"phages\", are viruses that specifically infect bacterial cells, and their interactions with the gut microbiome are receiving increased attention. Despite the recently revived interest in the gut phageome, it is still considered the \"dark matter\" of the gut, with more than 80% of viral genomes remaining uncharacterized. Today, research is focused on understanding the mechanisms by which phages influence the gut microbiota and their potential applications. Bacteriophages may regulate the relative abundance of bacterial communities, affect bacterial functions in various ways, and modulate mammalian host immunity. This review explores how phages can regulate bacterial functionality, particularly in gut commensals and pathogens, emphasizing their role in gut health and disease.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2481178"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752377","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}