Gut Microbes最新文献

{"title":"Microbiota-derived IPA alleviates intestinal mucosal inflammation through upregulating Th1/Th17 cell apoptosis in inflammatory bowel disease.","authors":"Han Gao, Mingming Sun, Ai Li, Qiaoyan Gu, Dengfeng Kang, Zhongsheng Feng, Xiaoyu Li, Xuehong Wang, Liang Chen, Hong Yang, Yingzi Cong, Zhanju Liu","doi":"10.1080/19490976.2025.2467235","DOIUrl":"10.1080/19490976.2025.2467235","url":null,"abstract":"<p><p>The gut microbiota-derived metabolite indole-3-propionic acid (IPA) plays an important role in maintaining intestinal mucosal homeostasis, while the molecular mechanisms underlying IPA regulation on mucosal CD4⁺ T cell functions in inflammatory bowel disease (IBD) remain elusive. Here we investigated the roles of IPA in modulating mucosal CD4⁺ T cells and its therapeutic potential in treatment of human IBD. Leveraging metabolomics and microbial community analyses, we observed that the levels of IPA-producing microbiota (e.g. <i>Peptostreptococcus</i>, <i>Clostridium</i>, and <i>Fournierella</i>) and IPA were decreased, while the IPA-consuming microbiota (e.g. <i>Parabacteroides</i>, <i>Erysipelatoclostridium</i>, and <i>Lachnoclostridium</i>) were increased in the feces of IBD patients than those in healthy donors. Dextran sulfate sodium (DSS)-induced acute colitis and CD45RB^highCD4⁺ T cell transfer-induced chronic colitis models were then established in mice and treated orally with IPA to study its role in intestinal mucosal inflammation <i>in vivo</i>. We found that oral administration of IPA attenuated mucosal inflammation in both acute and chronic colitis models in mice, as characterized by increased body weight, and reduced levels of pro-inflammatory cytokines (e.g. TNF-α, IFN-γ, and IL-17A) and histological scores in the colon. We further utilized RNA sequencing, molecular docking simulations, and surface plasmon resonance analyses and identified that IPA exerts its biological effects by interacting with heat shock protein 70 (HSP70), leading to inducing Th1/Th17 cell apoptosis. Consistently, ectopic expression of HSP70 in CD4⁺ T cells conferred resistance to IPA-induced Th1/Th17 cell apoptosis. Therefore, these findings identify a previously unrecognized pathway by which IPA modulates intestinal inflammation and provide a promising avenue for the treatment of IBD.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2467235"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433040","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":"Early life gut microbiome and its impact on childhood health and chronic conditions.","authors":"Harold Nunez, Pamela A Nieto, Ruben A Mars, Maryam Ghavami, Cheryl Sew Hoy, Kimberley Sukhum","doi":"10.1080/19490976.2025.2463567","DOIUrl":"10.1080/19490976.2025.2463567","url":null,"abstract":"<p><p>The development of the gut microbiome is crucial to human health, particularly during the first three years of life. Given its role in immune development, disturbances in the establishment process of the gut microbiome may have long term consequences. This review summarizes evidence for these claims, highlighting compositional changes of the gut microbiome during this critical period of life as well as factors that affect gut microbiome development. Based on human and animal data, we conclude that the early-life microbiome is a determinant of long-term health, impacting physiological, metabolic, and immune processes. The early-life gut microbiome field faces challenges. Some of these challenges are technical, such as lack of standardized stool collection protocols, inconsistent DNA extraction methods, and outdated sequencing technologies. Other challenges are methodological: small sample sizes, lack of longitudinal studies, and poor control of confounding variables. To address these limitations, we advocate for more robust research methodologies to better understand the microbiome's role in health and disease. Improved methods will lead to more reliable microbiome studies and a deeper understanding of its impact on health outcomes.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2463567"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364578","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":"Probiotic supplementation mitigates sex-dependent nociceptive changes and gut dysbiosis induced by prenatal opioid exposure.","authors":"Salma Singh, Yaa Abu, Danielle Antoine, Daniel Gomez, Junyi Tao, Bridget Truitt, Sabita Roy","doi":"10.1080/19490976.2025.2464942","DOIUrl":"10.1080/19490976.2025.2464942","url":null,"abstract":"<p><p>The gut microbiome has emerged as a promising target for modulating adverse effects of opioid exposure due to its significant role in health and disease. Opioid use disorder (OUD) has become increasingly prevalent, specifically in women of reproductive age, contributing to an increased incidence of offspring exposed to opioids in utero. Recent studies have shown that prenatal opioid exposure (POE) is associated with notable changes to the maternal gut microbiome, with subsequent implications for the offspring's microbiome and other adverse outcomes. However, the role of the gut microbiome in mediating sex-based differences in pain sensitivity has not yet been investigated. In this study, both male and female C57BL/6 offspring were used to determine sex-based differences in nociception and gut microbial composition as a result of POE. Our data reveals significant sex-based differences in offspring prenatally exposed to opioids. The gut microbiome of opioid-exposed females showed an enrichment of commensal bacteria including <i>Lactobacillus</i> compared to opioid-exposed males. Additionally, POE females demonstrated decreased nociceptive sensitivity, while males demonstrated increased nociceptive sensitivity. RNA sequencing of the prefrontal cortex showed sex-based differences in several canonical pathways, including an increase in the opioid signaling pathway of opioid-exposed females, which was not observed in males. Microbiome modification via maternal probiotic supplementation attenuated sex-based differences throughout the early stages of life. Together, our study provides further insight on sex-based differences arising from POE and highlights the pivotal role of the gut microbiome as a modifiable target for mitigating its negative effects.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2464942"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414041","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":"Failure of colonization following gut microbiota transfer exacerbates DSS-induced colitis.","authors":"Kevin L Gustafson, Trevor R Rodriguez, Zachary L McAdams, Lyndon M Coghill, Aaron C Ericsson, Craig L Franklin","doi":"10.1080/19490976.2024.2447815","DOIUrl":"10.1080/19490976.2024.2447815","url":null,"abstract":"<p><p>To study the impact of differing specific pathogen-free gut microbiomes (GMs) on a murine model of inflammatory bowel disease, selected GMs were transferred using embryo transfer (ET), cross-fostering (CF), and co-housing (CH). Prior work showed that the GM transfer method and the microbial composition of donor and recipient GMs can influence microbial colonization and disease phenotypes in dextran sodium sulfate-induced colitis. When a low richness GM was transferred to a recipient with a high richness GM via CH, the donor GM failed to successfully colonize, and a more severe disease phenotype resulted when compared to ET or CF, where colonization was successful. By comparing CH and gastric gavage for fecal material transfer, we isolated the microbial component of this effect and determined that differences in disease severity and survival were associated with microbial factors rather than the transfer method itself. Mice receiving a low richness GM via CH and gastric gavage exhibited greater disease severity and higher expression of pro-inflammatory immune mediators compared to those receiving a high richness GM. This study provides valuable insights into the role of GM composition and colonization in disease modulation.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2447815"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983417","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":"<i>Roseburia hominis</i> improves host metabolism in diet-induced obesity.","authors":"Wenli Huang, Wenyi Zhu, Yu Lin, Francis K L Chan, Zhilu Xu, Siew C Ng","doi":"10.1080/19490976.2025.2467193","DOIUrl":"10.1080/19490976.2025.2467193","url":null,"abstract":"<p><p>Next-generation live biotherapeutics are promising to aid the treatment of obesity and metabolic diseases. Here, we reported a novel anti-obesity probiotic candidate, <i>Roseburia hominis</i>, that was depleted in stool samples of obese subjects compared with lean controls, and its abundance was negatively correlated with body mass index and serum triglycerides. Supplementation of <i>R. hominis</i> prevented body weight gain and disorders of glucose and lipid metabolism, prevented fatty liver, inhibited white adipose tissue expansion and brown adipose tissue whitening in mice fed with high-fat diet, and boosted the abundance of lean-related species. The effects of <i>R. hominis</i> could be partially attributed to the production of nicotinamide riboside and upregulation of the Sirtuin1/mTOR signaling pathway. These results indicated that <i>R. homini</i>s is a promising candidate for the development of next-generation live biotherapeutics for the prevention of obesity and metabolic diseases.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2467193"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457592","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":"Inactivation of glutathione <i>S</i>-transferase alpha 4 blocks <i>Enterococcus faecalis</i>-induced bystander effect by promoting macrophage ferroptosis.","authors":"Yuanyuan Ju, Chunhua Ma, Lin Huang, Yumei Tao, Tianqi Li, Haibo Li, Mark M Huycke, Yonghong Yang, Xingmin Wang","doi":"10.1080/19490976.2025.2451090","DOIUrl":"10.1080/19490976.2025.2451090","url":null,"abstract":"<p><p><i>Enterococcus faecalis</i>-infected macrophages produce 4-hydroxynonenal (4-HNE) that mediates microbiota-induced bystander effect (MIBE) leading to colorectal cancer (CRC). Glutathione <i>S</i>-transferase alpha 4 (Gsta4), a specific detoxifying enzyme for 4-HNE, is overexpressed in human CRC and <i>E. faecalis</i>-induced murine CRC. However, the roles of Gsta4 in <i>E. faecalis</i>-induced colitis and CRC remain unclear. Herein, we demonstrate that Gsta4 is essential for MIBE by protecting macrophages from <i>E. faecalis</i>-induced ferroptosis. <i>E. faecalis</i> OG1RFSS was used to induce colitis in <i>Gsta4</i>^-/- and <i>Il10</i>^-/-<i>/Gsta4^-/-</i> mice by orogastric gavage. Ferroptosis was assessed in Gsta4-deficient murine macrophages. We found that, unlike <i>Il10</i>^-/- mice, <i>Gsta4^-/-</i> and <i>Il10</i>^-/-/<i>Gsta4</i>^-/- mice colonized with <i>E. faecalis</i> failed to develop colitis or CRC. Immunofluorescent staining showed a reduction of macrophages in the lamina propria of <i>E. faecalis</i>-colonized <i>Il10</i>^-/-/<i>Gsta4</i>^-/- mice, as well as decreased Gpx4 expression, indicating the occurrence of ferroptosis. Ferroptosis was further confirmed in <i>Gsta4</i>-deficient murine macrophages infected with <i>E. faecalis</i>. Moreover, Gsta4 inactivation induced the upregulation of Hmox1 and phosphorylated c-Jun while blocked Nos2 expression, leading to the accumulation of intracellular ferrous iron, lipid peroxidation and, eventually, ferroptosis. Finally, Mapk8, as a ferroptosis driver, was remarkably elevated in <i>E. faecalis</i>-infected <i>Gsta4</i>-deficient macrophages. These results suggest that Gsta4 inactivation blocks MIBE by eliminating macrophages, thereby attenuates <i>E. faecalis</i>-induced colitis and CRC.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2451090"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055916","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":"<i>Fusobacterium nucleatum</i> upregulates the immune inhibitory receptor <i>PD-L1</i> in colorectal cancer cells via the activation of ALPK1.","authors":"Coco Duizer, Moniek Salomons, Merel van Gogh, Sanne Gräve, Freke A Schaafsma, Maaike J Stok, Merel Sijbranda, Raghuvandhanan Kumarasamy Sivasamy, Rob J L Willems, Marcel R de Zoete","doi":"10.1080/19490976.2025.2458203","DOIUrl":"10.1080/19490976.2025.2458203","url":null,"abstract":"<p><p><i>Fusobacterium nucleatum</i> is a Gram-negative oncobacterium that is associated with colorectal cancer. The molecular mechanisms utilized by <i>F. nucleatum</i> to promote colorectal tumor development have largely focused on adhesin-mediated binding to the tumor tissue and on the pro-inflammatory capacity of <i>F. nucleatum</i>. However, the exact manner in which <i>F. nucleatum</i> promotes inflammation in the tumor microenvironment and subsequent tumor promotion remains underexplored. Here, we show that both living <i>F. nucleatum</i> and sterile <i>F. nucleatum-</i>conditioned medium promote CXCL8 release from the intestinal adenocarcinoma HT-29 cell line. We determined that the observed pro-inflammatory effect was ALPK1-dependent in both HEK293 and HT-29 cells and that the released <i>F. nucleatum</i> molecule had characteristics that match those of the pro-inflammatory ALPK1 ligand ADP-heptose or related heptose phosphates. In addition, we determined that not only <i>F. nucleatum</i> promoted an ALPK1-dependent pro-inflammatory environment but also other <i>Fusobacterium</i> species such as <i>F. varium</i>, <i>F. necrophorum</i> and <i>F. gonidiaformans</i> generated similar effects, indicating that ADP-heptose or related heptose phosphate secretion is a conserved feature of the <i>Fusobacterium</i> genus. By performing transcriptional analysis of ADP-heptose stimulated HT-29 cells, we found several inflammatory and cancer-related pathways to be differentially regulated, including DNA mismatch repair genes and the immune inhibitory receptor <i>PD-L1</i>. Finally, we show that stimulation of HT-29 cells with <i>F. nucleatum</i> resulted in an ALPK1-dependent upregulation of <i>PD-L1</i>. These results aid in our understanding of the mechanisms by which <i>F. nucleatum</i> can affect tumor development and therapy and pave the way for future therapeutic approaches.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2458203"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11784648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064923","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":"<i>Bifidobacterium</i> inhibits the progression of colorectal tumorigenesis in mice through fatty acid isomerization and gut microbiota modulation.","authors":"Yang Chen, Huiting Fang, Haiqin Chen, Xiaoming Liu, Jianxin Zhao, Catherine Stanton, R Paul Ross, Wei Chen, Bo Yang","doi":"10.1080/19490976.2025.2464945","DOIUrl":"10.1080/19490976.2025.2464945","url":null,"abstract":"<p><p>Colorectal cancer (CRC) represents the third most common cancer worldwide. Consequently, there is an urgent need to identify novel preventive and therapeutic strategies for CRC. This study aimed to screen for beneficial bacteria that have a preventive effect on CRC and to elucidate the potential mechanisms. Initially, we compared gut bacteria and bacterial metabolites of healthy volunteers and CRC patients, which demonstrated that intestinal conjugated linoleic acid (CLA), butyric acid, and <i>Bifidobacterium</i> in CRC patients were significantly lower than those in healthy volunteers, and these indicators were significantly negatively correlated with CRC. Next, spontaneous CRC mouse model were conducted to explore the effect of supplemental CLA-producing <i>Bifidobacterium</i> on CRC. Supplementation of mice with CLA-producing <i>Bifidobacterium breve</i> CCFM683 and <i>B. pseudocatenulatum</i> MY40C significantly prevented CRC. Moreover, molecular approaches demonstrated that CLA and the CLA-producing gene, <i>bbi</i>, were the key metabolites and genes for CCFM683 to prevent CRC. Inhibitor intervention results showed that PPAR-γ was the key receptor for preventing CRC. CCFM683 inhibited the NF-κB signaling pathway, up-regulated MUC2, Claudin-1, and ZO-1, and promoted tumor cell apoptosis via the CLA-PPAR-γ axis. Additionally, fecal microbiota transplantation (FMT) and metagenomic analysis showed that CCFM683 up-regulated <i>Odoribacter splanchnicus</i> through CLA production, which then prevented CRC by producing butyric acid, up-regulating TJ proteins, regulating cytokines, and regulating gut microbiota. These results will contribute to the clinical trials of <i>Bifidobacterium</i> and the theoretical research and development of CRC dietary products.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2464945"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382296","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":"<i>Salmonella</i> utilizes L-arabinose to silence virulence gene expression for accelerated pathogen growth within the host.","authors":"Jingchen Yu, Huang Tang, Yana Chen, Zuoqiang Wang, Wanqiu Huang, Tao Zhou, Bingjie Wen, Chengyue Wang, Shuang Gu, Jinjing Ni, Jing Tao, Danni Wang, Jie Lu, Qing Xie, Yu-Feng Yao","doi":"10.1080/19490976.2025.2467187","DOIUrl":"10.1080/19490976.2025.2467187","url":null,"abstract":"<p><p>Carbon source is an important nutrient for bacteria to sustain growth and often acts as a signal that modulates virulence expression. L-arabinose is produced by plants and plays an important role in regulating the global gene expression of bacteria. Previously, we have shown that L-arabinose induces a more severe systemic infection in <i>Salmonella</i>-infected mice with normal microbiota, but does not affect the disease progression in mice with microbiota depleted by antibiotic treatment. The underlying mechanism remains elusive. In this study, we demonstrate that L-arabinose represses the expression of <i>Salmonella</i> type III secretion system 1 (T3SS-1) genes by negatively regulating the activity of the cyclic 3' 5'-AMP (cAMP)-cAMP receptor protein (CRP) complex. The cAMP-CRP complex can activate ribosome-associated inhibitor A, encoded by <i>yfiA</i>, to maintain the stability of HilD, a key transcriptional regulator of T3SS-1. L-arabinose supplementation promotes <i>Salmonella</i> initial bloom in the antibiotic-pretreated mouse gut and ultimately compensates for reduced virulence within the host. These results decipher the molecular mechanism by which cAMP-CRP directs regulatory changes of virulence in response to L-arabinose in <i>Salmonella</i>. It further implies that <i>Salmonella</i> exploits L-arabinose both as a nutrient and a regulatory signal to maintain a balance between growth and virulence within the host.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2467187"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425259","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":"Protection against experimental necrotizing enterocolitis by fecal filtrate transfer requires an active donor virome.","authors":"Malene Roed Spiegelhauer, Simone Margaard Offersen, Xiaotian Mao, Michela Gambino, Dennis Sandris Nielsen, Duc Ninh Nguyen, Anders Brunse","doi":"10.1080/19490976.2025.2486517","DOIUrl":"https://doi.org/10.1080/19490976.2025.2486517","url":null,"abstract":"<p><p>Necrotizing enterocolitis (NEC) remains a frequent catastrophic disease in preterm infants, and fecal filtrate transfer (FFT) has emerged as a promising prophylactic therapy. This study explored the role of virome viability for the protective effect of FFT. Using ultraviolet (UV) irradiation, we established a viral inactivation protocol and administered FFT, UV-inactivated FFT (iFFT) or sterile saline orally to preterm piglets at risk for experimental NEC. The gut pathology and barrier properties were assessed, while the microbiome was explored by 16S rRNA amplicon and metavirome sequencing. Like in prior studies, FFT reduced NEC severity and intestinal inflammation, while these effects were absent in the iFFT group. Unexpectedly, piglets receiving FFT exhibited mild side effects in the form of early-onset diarrhea. The FFT also converged the gut colonization by increased viral heterogeneity and a reduced abundance of pathobionts like <i>Clostridium perfringens</i> and <i>Escherichia</i>. In contrast, the gut microbiome of iFFT recipients diverged from both FFT and the controls. These findings highlight the clear distinction between the ability of active and inactivate viromes to modulate gut microbiota and decrease pathology. The efficacy of FFT may be driven by active bacteriophages, and loss of virome activity could have consequences for the treatment efficacy.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2486517"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11988273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011434","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}