Gut Microbes最新文献

{"title":"Microbial micronutrient sharing, gut redox balance and keystone taxa as a basis for a new perspective to solutions targeting health from the gut.","authors":"Robert E Steinert, Ateequr Rehman, Mehdi Sadaghian Sadabad, Alessio Milanese, Jonas Wittwer-Schegg, Jeremy P Burton, Anneleen Spooren","doi":"10.1080/19490976.2025.2477816","DOIUrl":"10.1080/19490976.2025.2477816","url":null,"abstract":"<p><p>In health, the gut microbiome functions as a stable ecosystem maintaining overall balance and ensuring its own survival against environmental stressors through complex microbial interaction. This balance and protection from stressors is maintained through interactions both within the bacterial ecosystem as well as with its host. As a consequence, the gut microbiome plays a critical role in various physiological processes including maintaining the structure and function of the gut barrier, educating the gut immune system, and modulating the gut motor, digestive/absorptive, as well as neuroendocrine system all of which are crucial for human health and disease pathogenesis. Pre- and probiotics, widely available and clinically established, offer various health benefits primarily by beneficially modulating the gut microbiome. However, their clinical outcomes can vary significantly due to differences in host physiology, diets, individual microbiome compositions, and other environmental factors. This perspective paper highlights emerging scientific insights into the importance of microbial micronutrient sharing, gut redox balance, keystone species, and the gut barrier in maintaining a diverse and functional microbial ecosystem, and their relevance to human health. We propose a novel approach that targets microbial ecosystems and keystone taxa performance by supplying microbial micronutrients in the form of colon-delivered vitamins, and precision prebiotics [e.g. human milk oligosaccharides (HMOs) or synthetic glycans] as components of precisely tailored ingredient combinations to optimize human health. Such a strategy may effectively support and stabilize microbial ecosystems, providing a more robust and consistent approach across various individuals and environmental conditions, thus, overcoming the limitations of current single biotic solutions.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2477816"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639523","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":"Extracellular vesicles of <i>Limosilactobacillus fermentum</i> SLAM216 ameliorate skin symptoms of atopic dermatitis by regulating gut microbiome on serotonin metabolism.","authors":"Hyejin Choi, Min-Jin Kwak, Youbin Choi, An Na Kang, Daye Mun, Ju Young Eor, Mi Ri Park, Sangnam Oh, Younghoon Kim","doi":"10.1080/19490976.2025.2474256","DOIUrl":"10.1080/19490976.2025.2474256","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a globally prevalent chronic inflammatory skin disorder. Its pathogenesis remains incompletely understood, resulting in considerable therapeutic challenges. Recent studies have highlighted the significance of the interaction between AD and gut microbiome. In this study, we investigated the effects of probiotic-derived extracellular vesicles on AD. Initially, we isolated and characterized extracellular vesicles from <i>Limosilactobacillus fermentum</i> SLAM 216 (LF216EV) and characterized their composition through multi-omics analysis. Gene ontology (GO) and pathway analysis classified LF216EV proteins into biological processes, molecular functions, and cellular components. Importantly, specific abundance in linoleic, oleic, palmitic, sebacic, and stearic acids indicating upregulated fatty acid metabolism were observed by metabolomic analysis. Furthermore, featured lipid profiling including AcylGlcADG and ceramide were observed in LF216EV. Importantly, in an atopic dermatitis-like cell model induced by TNFα/IFNγ, LF216EV significantly modulated the expression of immune regulatory genes (TSLP, TNFα, IL-6, IL-1β, and MDC), indicating its potential functionality in atopic dermatitis. LF216EV alleviated AD-like phenotypes, such as redness, scaling/dryness, and excoriation, induced by DNCB. Histopathological analysis revealed that LF216EV decreased epidermal thickness and mast cell infiltration in the dermis. Furthermore, LF216EV administration reduced mouse scratching and depression-related behaviors, with a faster onset than the classical treatment with dexamethasone. In the quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we observed a significant increase in the expression levels of <i>htrb2c</i>, <i>sert</i>, and <i>tph-1</i>, genes associated with serotonin, in the skin and gut of the LF216EV-treated group, along with a significant increase in the total serum serotonin levels. Gut microbiome analysis of the LF216EV-treated group revealed an altered gut microbiota profile. Correlation analysis revealed that the genera <i>Limosilactobacillus</i> and <i>Desulfovibrio</i> were associated with differences in the intestinal metabolites, including serotonin. Our findings demonstrate that LF216EV mitigates AD-like symptoms by promoting serotonin synthesis through the modulation of gut microbiota and metabolome composition.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2474256"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541433","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":"Gut microbiota in hepatocellular carcinoma immunotherapy: immune microenvironment remodeling and gut microbiota modification.","authors":"Mingyao Huang, Quansong Ji, Huiyan Huang, Xiaoqian Wang, Lin Wang","doi":"10.1080/19490976.2025.2486519","DOIUrl":"10.1080/19490976.2025.2486519","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited treatment options at advanced stages. The gut microbiota, a diverse community of microorganisms residing in the gastrointestinal tract, plays a pivotal role in regulating immune responses through the gut-liver axis. Emerging evidence underscores its impact on HCC progression and the efficacy of immunotherapy. This review explores the intricate interactions between gut microbiota and the immune system in HCC, with a focus on key immune cells and pathways involved in tumor immunity. Additionally, it highlights strategies for modulating the gut microbiota - such as fecal microbiota transplantation, dietary interventions, and probiotics - as potential approaches to enhancing immunotherapy outcomes. A deeper understanding of these mechanisms could pave the way for novel therapeutic strategies aimed at improving patient prognosis.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2486519"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752382","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":"M28 family peptidase derived from <i>Peribacillus frigoritolerans</i> initiates trained immunity to prevent MRSA via the complosome-phosphatidylcholine axis.","authors":"Cheng-Kai Zhou, Zhen-Zhen Liu, Zi-Ran Peng, Xue-Yue Luo, Xiao-Mei Zhang, Jian-Gang Zhang, Liang Zhang, Wei Chen, Yong-Jun Yang","doi":"10.1080/19490976.2025.2484386","DOIUrl":"10.1080/19490976.2025.2484386","url":null,"abstract":"<p><p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) represents a major global health threat due to its resistance to conventional antibiotics. The commensal microbiota maintains a symbiotic relationship with the host, playing essential roles in metabolism, energy regulation, immune modulation, and pathogen control. Mammals harbor a wide range of commensal bacteria capable of producing unique metabolites with potential therapeutic properties. This study demonstrated that M28 family peptidase (M28), derived from commensal bacteria <i>Peribacillus frigoritolerans</i> (<i>P. f</i>), provided protective effects against MRSA-induced pneumonia. M28 enhanced the phagocytosis and bactericidal activity of macrophages by inducing trained immunity. RNA sequencing and metabolomic analyses identified the CFB-C3a-C3aR-HIF-1α axis-mediated phosphatidylcholine accumulation as the key mechanism for M28-induced trained immunity. Phosphatidylcholine, like M28, also induced trained immunity. To enhance M28-mediated therapeutic potential, it was encapsulated in liposomes (M28-LNPs), which exhibited superior immune-stimulating properties compared to M28 alone. In vivo experiments revealed that M28-LNPs significantly reduced bacterial loads and lung damage following MRSA infection, which also provided enhanced protection against <i>Klebsiella pneumoniae</i> and <i>Candida albicans</i>. We first confirmed a link between complement activation and trained immunity, offering valuable insights into the treatment and prevention of complement-related autoimmune diseases.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2484386"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11959922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752384","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":"Reutericyclin, a specialized metabolite of <i>Limosilactobacillus reuteri</i>, mitigates risperidone-induced weight gain in mice.","authors":"Fatima A Aboulalazm, Alexis B Kazen, Orlando deLeon, Susanne Müller, Fatima L Saravia, Valery Lozada-Fernandez, Matthew A Hadiono, Robert F Keyes, Brian C Smith, Stephanie L Kellogg, Justin L Grobe, Tammy L Kindel, John R Kirby","doi":"10.1080/19490976.2025.2477819","DOIUrl":"https://doi.org/10.1080/19490976.2025.2477819","url":null,"abstract":"<p><p>The role of xenobiotic disruption of microbiota, corresponding dysbiosis, and potential links to host metabolic diseases are of critical importance. In this study, we used a widely prescribed antipsychotic drug, risperidone, known to influence weight gain in humans, to induce weight gain in C57BL/6J female mice. We hypothesized that microbes essential for maintaining gut homeostasis and energy balance would be depleted following treatment with risperidone, leading to enhanced weight gain relative to controls. Thus, we performed metagenomic analyses on stool samples to identify microbes that were excluded in risperidone-treated animals but remained present in controls. We identified multiple taxa including <i>Limosilactobacillus reuteri</i> as a candidate for further study. Oral supplementation with <i>L. reuteri</i> protected against risperidone-induced weight gain (RIWG) and was dependent on cellular production of a specialized metabolite, reutericyclin. Further, synthetic reutericyclin was sufficient to mitigate RIWG. Both synthetic reutericyclin and <i>L. reuteri</i> restored energy balance in the presence of risperidone to mitigate excess weight gain and induce shifts in the microbiome associated with leanness. In total, our results identify reutericyclin production by <i>L. reuteri</i> as a potential probiotic to restore energy balance induced by risperidone and to promote leanness.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2477819"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795245","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":"The impact of gut microbial short-chain fatty acids on colorectal cancer development and prevention.","authors":"Boobalan Thulasinathan, Kanve N Suvilesh, Sumanas Maram, Erik Grossmann, Yezaz Ghouri, Emma Pernas Teixeiro, Joshua Chan, Jussuf T Kaif, Satyanarayana Rachagani","doi":"10.1080/19490976.2025.2483780","DOIUrl":"https://doi.org/10.1080/19490976.2025.2483780","url":null,"abstract":"<p><p>Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2483780"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795248","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":"Identifying the location-dependent adipose tissue bacterial DNA signatures in obese patients that predict body weight loss.","authors":"Matthieu Minty, Alberic Germain, Jiuwen Sun, Gracia Kaglan, Florence Servant, Benjamin Lelouvier, Emiri Misselis, Radu Mircea Neagoe, Menghini Rossella, Marina Cardellini, Rémy Burcelin, Massimo Federici, José Manuel Fernandez-Real, Vincent Blasco-Baque","doi":"10.1080/19490976.2024.2439105","DOIUrl":"https://doi.org/10.1080/19490976.2024.2439105","url":null,"abstract":"<p><p>Recent sets of evidence have described profiles of 16S rDNA sequences in host tissues, notably in fat pads that are significantly overrepresented and can serve as signatures of metabolic disease. However, these recent and original observations need to be further detailed and functionally defined. Here, using state-of-the-art targeted DNA sequencing and discriminant predictive approaches, we describe, from the longitudinal FLORINASH cohort of patients who underwent bariatric surgery, visceral, and subcutaneous fat pad-specific bacterial 16SrRNA signatures. The corresponding <i>Porphyromonadaceae</i>, <i>Campylobacteraceae</i>, <i>Prevotellaceae</i>, <i>Actimomycetaceae</i>, <i>Veillonellaceae</i>, <i>Anaerivoracaceae</i>, <i>Fusobacteriaceae</i>, and the <i>Clostridium family XI</i> 16SrRNA DNA segment profiles are signatures of the subcutaneous adipose depot while <i>Pseudomonadaceae</i> and <i>Micrococcacecae</i>, 16SrRNA DNA sequence profiles characterize the visceral adipose depot. In addition, we have further identified that a specific pre-bariatric surgery adipose tissue bacterial DNA signature predicts the efficacy of body weight loss in obese patients 5-10 years after the surgery. 16SrRNA signatures discriminate (ROC ~ 1) the patients who did not maintain bodyweight loss and those who did. Second, from the 16SrRNA sequences we infer potential pathways suggestive of catabolic biochemical activities that could be signatures of subcutaneous adipose depots that predict body weight loss.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2439105"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876909","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":"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":"https://doi.org/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":"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}