Gut Microbes最新文献

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Mucosal washes are useful for sampling intestinal mucus-associated microbiota despite low biomass. 尽管粘膜清洗液的生物量较低,但对肠道粘液相关微生物群采样很有用。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-02-20 DOI: 10.1080/19490976.2025.2464296
Jennifer N Martinez-Medina, Fereshteh Ghazisaeedi, Catharina Kramer, Jörn F Ziegler, Victoria McParland, Paul W Mönch, Britta Siegmund, Víctor Hugo Jarquín-Díaz, Marcus Fulde, Sofia K Forslund-Startceva
{"title":"Mucosal washes are useful for sampling intestinal mucus-associated microbiota despite low biomass.","authors":"Jennifer N Martinez-Medina, Fereshteh Ghazisaeedi, Catharina Kramer, Jörn F Ziegler, Victoria McParland, Paul W Mönch, Britta Siegmund, Víctor Hugo Jarquín-Díaz, Marcus Fulde, Sofia K Forslund-Startceva","doi":"10.1080/19490976.2025.2464296","DOIUrl":"10.1080/19490976.2025.2464296","url":null,"abstract":"<p><p>Understanding the dynamic relationship between mucus-associated microbiota and host health is critical. However, studies predominantly using stool samples may not accurately represent these bacterial communities. Here, we investigated the mucus-associated microbiota in the gastrointestinal tract of mice and the terminal ileum of humans using different sample types: mucosal washes, brushes, scrapings, and intestinal contents in mice and biopsies, brushes and mucosal washes in humans. We used DNA quantification and 16S rRNA amplicon sequencing to evaluate the comparability of the information yielded from the different sample types under a controlled benchmark. In mice, mucosal washes and brushes had comparative bacterial DNA and host DNA contamination than scraping samples. Similarly, in humans, washes outperformed biopsies in bacterial DNA content. Read counts and microbiota alpha diversity remained remarkably similar in mice and between brushes and washes in humans. The composition of the microbiota varied based on the subsegment and sample type in mice and sample type in humans. We conclude that washes and brushes reduce host contamination without inducing substantial compositional bias when sampling mucosal microbiota. Our findings suggest that mucosal washes and brushes are a viable alternative to biopsies in humans and scrapings in mice, thereby improving the transferability of results across hosts. Our study highlights the importance of focusing on mucus-associated microbiota to better capture host-microbiome interactions at their closer interface.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2464296"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467872","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}
引用次数: 0
Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism. 自闭症儿童粪便微生物群移植后沿肠-脑轴小鼠品系特异性反应。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-01-07 DOI: 10.1080/19490976.2024.2447822
Naika Prince, Lucia N Peralta Marzal, Léa Roussin, Magali Monnoye, Catherine Philippe, Elise Maximin, Sabbir Ahmed, Karoliina Salenius, Jake Lin, Reija Autio, Youri Adolfs, R Jeroen Pasterkamp, Johan Garssen, Laurent Naudon, Sylvie Rabot, Aletta D Kraneveld, Paula Perez-Pardo
{"title":"Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism.","authors":"Naika Prince, Lucia N Peralta Marzal, Léa Roussin, Magali Monnoye, Catherine Philippe, Elise Maximin, Sabbir Ahmed, Karoliina Salenius, Jake Lin, Reija Autio, Youri Adolfs, R Jeroen Pasterkamp, Johan Garssen, Laurent Naudon, Sylvie Rabot, Aletta D Kraneveld, Paula Perez-Pardo","doi":"10.1080/19490976.2024.2447822","DOIUrl":"10.1080/19490976.2024.2447822","url":null,"abstract":"<p><p>Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, the molecular mechanisms of the condition remain unknown. As intestinal problems and gut microbiota dysbiosis are associated with ASD development and severity, recent studies have focused on elucidating the microbiota-gut-brain axis' involvement. This study aims to explore mechanisms through which gut microbiota might influence ASD. Briefly, we depleted the microbiota of conventional male BALB/cAnNCrl (Balb/c) and C57BL/6J (BL/6) mice prior to human fecal microbiota transplantation (hFMT) with samples from children with ASD or their neurotypical siblings. We found mouse strain-specific responses to ASD hFMT. Notably, Balb/c mice exhibit decreased exploratory and social behavior, and show evidence of intestinal, systemic, and central inflammation accompanied with metabolic shifts. BL/6 mice show less changes after hFMT. Our results reveal that gut microbiota alone induce changes in ASD-like behavior, and highlight the importance of mouse strain selection when investigating multifactorial conditions like ASD.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2447822"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947805","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}
引用次数: 0
Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection.
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-03-12 DOI: 10.1080/19490976.2025.2476562
Anna Clapp Organski, Bartek Rajwa, Anjali Reddivari, Joan S Jorgensen, Tzu-Wen L Cross
{"title":"Gut microbiome-driven regulation of sex hormone homeostasis: a potential neuroendocrine connection.","authors":"Anna Clapp Organski, Bartek Rajwa, Anjali Reddivari, Joan S Jorgensen, Tzu-Wen L Cross","doi":"10.1080/19490976.2025.2476562","DOIUrl":"10.1080/19490976.2025.2476562","url":null,"abstract":"<p><p>The gut microbiome is known to have a bidirectional relationship with sex hormone homeostasis; however, its role in mediating interactions between the primary regulatory axes of sex hormones and their productions is yet to be fully understood. We utilized both conventionally raised and gnotobiotic mouse models to investigate the regulatory role of the gut microbiome on the hypothalamic-pituitary-gonadal (HPG) axis. Male and female conventionally raised mice underwent surgical modifications as follows: (1) hormonally intact controls; (2) gonadectomized males and females; (3) gonadectomized males and females supplemented with testosterone and estrogen, respectively. Fecal samples from these mice were used to colonize sex-matched, intact, germ-free recipient mice through fecal microbiota transplant (FMT). Serum gonadotropins, gonadal sex hormones, cecal microbiota, and the serum global metabolome were assessed. FMT recipients of gonadectomized-associated microbiota showed lower circulating gonadotropin levels than recipients of intact-associated microbiota, opposite to that of FMT donors. FMT recipients of gonadectomized-associated microbiota also had greater testicular weights compared to recipients of intact-associated microbiota. The gut microbiota composition of recipient mice differed significantly based on the FMT received, with the male microbiota having a more concerted impact in response to changes in the HPG axis. Network analyses showed that multiple metabolically unrelated pathways may be involved in driving differences in serum metabolites due to sex and microbiome received in the recipient mice. In sum, our findings indicate that the gut microbiome responds to the HPG axis and subsequently modulates its feedback mechanisms. A deeper understanding of interactions between the gut microbiota and the neuroendocrine-gonadal system may contribute to the development of therapies for sexually dimorphic diseases.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2476562"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604541","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}
引用次数: 0
Dysregulation of gut microbiota stimulates NETs-driven HCC intrahepatic metastasis: therapeutic implications of healthy faecal microbiota transplantation.
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-03-18 DOI: 10.1080/19490976.2025.2476561
Zhe Deng, Si Mei, Zhaoguang Ouyang, Ruoyu Wang, Lihuai Wang, Bo Zou, Jingjing Dai, Kexin Mao, Qian Li, Qianqian Guo, Chun Yi, Fanying Meng, Mingxia Xie, Xue Zhang, Rongrong Wang, Tianhao Deng, Zhenyu Wang, Xiaozheng Li, Qing Wang, Bin Liu, Xuefei Tian
{"title":"Dysregulation of gut microbiota stimulates NETs-driven HCC intrahepatic metastasis: therapeutic implications of healthy faecal microbiota transplantation.","authors":"Zhe Deng, Si Mei, Zhaoguang Ouyang, Ruoyu Wang, Lihuai Wang, Bo Zou, Jingjing Dai, Kexin Mao, Qian Li, Qianqian Guo, Chun Yi, Fanying Meng, Mingxia Xie, Xue Zhang, Rongrong Wang, Tianhao Deng, Zhenyu Wang, Xiaozheng Li, Qing Wang, Bin Liu, Xuefei Tian","doi":"10.1080/19490976.2025.2476561","DOIUrl":"10.1080/19490976.2025.2476561","url":null,"abstract":"<p><p>The stringent regulation of intrahepatic metastases is essential for improving survival outcomes in patients with hepatocellular carcinoma (HCC). This study investigated the impact of gut microbiota on intrahepatic metastasis of HCC and evaluated the therapeutic potential of healthy fecal microbiota transplantation (FMT). Dysregulation of the gut microbiota, characterized by a significant reduction in the abundance of beneficial bacteria, such as <i>Anaerotruncus colihominis</i> and <i>Dysosmobacter welbionis</i>, was observed in patients with intrahepatic metastatic HCC. A human flora-associated (HFA) intrahepatic metastatic HCC mouse model was successfully established through consecutive 4 weeks of human-mouse FMT. Dysregulation of gut microbiota promoted intrahepatic metastasis in the mouse model, primarily by enhancing neutrophil-mediated inflammatory responses and lead to excessive formation of neutrophil extracellular traps (NETs). Consequently, it promoted tumor vascular growth and tissue necrosis, resulting in intrahepatic metastasis of HCC. Notably, FMT from healthy donors mitigated these pathological processes. This study elucidated the role and mechanism of dysregulated gut microbiota in promoting intrahepatic metastasis of HCC. Healthy FMT emerges as a promising novel therapeutic strategy for preventing and treating intrahepatic metastasis of HCC.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2476561"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657016","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}
引用次数: 0
Biofilm-associated proteins: from the gut biofilms to neurodegeneration.
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-02-03 DOI: 10.1080/19490976.2025.2461721
Jaione Valle
{"title":"Biofilm-associated proteins: from the gut biofilms to neurodegeneration.","authors":"Jaione Valle","doi":"10.1080/19490976.2025.2461721","DOIUrl":"10.1080/19490976.2025.2461721","url":null,"abstract":"<p><p>Human microbiota form a biofilm with substantial consequences for health and disease. Numerous studies have indicated that microbial communities produce functional amyloids as part of their biofilm extracellular scaffolds. The overlooked interplay between bacterial amyloids and the host may have detrimental consequences for the host, including neurodegeneration. This work gives an overview of the biofilm-associated amyloids expressed by the gut microbiota and their potential role in neurodegeneration. It discusses the biofilm-associated proteins (BAPs) of the gut microbiota, maps the amyloidogenic domains of these proteins, and analyzes the presence of <i>bap</i> genes within accessory genomes linked with transposable elements. Furthermore, the evidence supporting the existence of amyloids in the gut are presented. Finally, it explores the potential interactions between BAPs and α-synuclein, extending the literature on amyloid cross-kingdom interactions. Based on these findings, this study propose that BAP amyloids act as transmissible catalysts, facilitating the misfolding, accumulation, and spread of α-synuclein aggregates. This review contributes to the understanding of complex interactions among the microbiota, transmissible elements, and host, which is crucial for developing novel therapeutic approaches to combat microbiota-related diseases and improve overall health outcomes.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2461721"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079036","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}
引用次数: 0
Upregulation of Lactobacillus spp. in gut microbiota as a novel mechanism for environmental eustress-induced anti-pancreatic cancer effects.
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-02-23 DOI: 10.1080/19490976.2025.2470372
Yiyi Liang, Min Du, Xin Li, Jian Gao, Qian Li, Huimin Li, Jin Li, Xiang Gao, Hui Cong, Yimeng Huang, Xinran Li, Liwei Wang, Jiujie Cui, Yu Gan, Hong Tu
{"title":"Upregulation of <i>Lactobacillus spp</i>. in gut microbiota as a novel mechanism for environmental eustress-induced anti-pancreatic cancer effects.","authors":"Yiyi Liang, Min Du, Xin Li, Jian Gao, Qian Li, Huimin Li, Jin Li, Xiang Gao, Hui Cong, Yimeng Huang, Xinran Li, Liwei Wang, Jiujie Cui, Yu Gan, Hong Tu","doi":"10.1080/19490976.2025.2470372","DOIUrl":"10.1080/19490976.2025.2470372","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited effective treatment options. Emerging evidence links enriched environment (EE)-induced eustress to PDAC inhibition. However, the underlying mechanisms remain unclear. In this study, we explored the role of gut microbiota in PDAC-suppressive effects of EE. We demonstrated that depletion of gut microbiota with antibiotics abolished EE-induced tumor suppression, while fecal microbiota transplantation (FMT) from EE mice significantly inhibited tumor growth in both subcutaneous and orthotopic PDAC models housed in standard environment. 16S rRNA sequencing revealed that EE enhanced gut microbiota diversity and selectively enriched probiotic <i>Lactobacillus</i>, particularly <i>L. reuteri</i>. Treatment with <i>L. reuteri</i> significantly suppressed PDAC tumor growth and increased natural killer (NK) cell infiltration into the tumor microenvironment. Depletion of NK cells alleviated the anti-tumor effects of <i>L. reuteri</i>, underscoring the essential role of NK cell-mediated immunity in anti-tumor response. Clinical analysis of PDAC patients showed that higher fecal <i>Lactobacillus</i> abundance correlated with improved progression-free and overall survival, further supporting the therapeutic potential of <i>L. reuteri</i> in PDAC. Overall, this study identifies gut microbiota as a systemic regulator of PDAC under psychological stress. Supplementation of psychobiotic <i>Lactobacillus</i> may offer a novel therapeutic strategy for PDAC.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2470372"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11853549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482959","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}
引用次数: 0
Assessing live microbial therapeutic transmission. 评估活微生物治疗传播。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-01-02 DOI: 10.1080/19490976.2024.2447836
Jeremiah J Faith
{"title":"Assessing live microbial therapeutic transmission.","authors":"Jeremiah J Faith","doi":"10.1080/19490976.2024.2447836","DOIUrl":"10.1080/19490976.2024.2447836","url":null,"abstract":"<p><p>The development of fecal microbiota transplantation and defined live biotherapeutic products for the treatment of human disease has been an empirically driven process yielding a notable success of approved drugs for the treatment of recurrent <i>Clostridioides difficile</i> infection. Assessing the potential of this therapeutic modality in other indications with mixed clinical results would benefit from consistent quantitative frameworks to characterize drug potency and composition and to assess the impact of dose and composition on the frequency and duration of strain engraftment. Monitoring these drug properties and engraftment outcomes would help identify minimally sufficient sets of microbial strains to treat disease and provide insights into the intersection between microbial function and host physiology. Broad and correct usage of strain detection methods is essential to this advancement. This article describes strain detection approaches, where they are best applied, what data they require, and clinical trial designs that are best suited to their application.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2447836"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921237","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}
引用次数: 0
Faecalibacterium prausnitzii regulates carbohydrate metabolic functions of the gut microbiome in C57BL/6 mice. prausnitzii粪杆菌调节C57BL/6小鼠肠道微生物组的碳水化合物代谢功能。
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-01-22 DOI: 10.1080/19490976.2025.2455503
Peiling Geng, Ni Zhao, Yufan Zhou, Reuben S Harris, Yong Ge
{"title":"<i>Faecalibacterium prausnitzii</i> regulates carbohydrate metabolic functions of the gut microbiome in C57BL/6 mice.","authors":"Peiling Geng, Ni Zhao, Yufan Zhou, Reuben S Harris, Yong Ge","doi":"10.1080/19490976.2025.2455503","DOIUrl":"https://doi.org/10.1080/19490976.2025.2455503","url":null,"abstract":"<p><p>The probiotic impact of microbes on host metabolism and health depends on both host genetics and bacterial genomic variation. <i>Faecalibacterium prausnitzii</i> is the predominant human gut commensal emerging as a next-generation probiotic. Although this bacterium exhibits substantial intraspecies diversity, it is unclear whether genetically distinct <i>F. prausnitzii</i> strains might lead to functional differences in the gut microbiome. Here, we isolated and characterized a novel <i>F. prausnitzii</i> strain (UT1) that belongs to the most prevalent but underappreciated phylogenetic clade in the global human population. Genome analysis showed that this butyrate-producing isolate carries multiple putative mobile genetic elements, a clade-specific defense system, and a range of carbohydrate catabolic enzymes. Multiomic approaches were used to profile the impact of UT1 on the gut microbiome and associated metabolic activity of C57BL/6 mice at homeostasis. Both 16S rRNA and metagenomic sequencing demonstrated that oral administration of UT1 resulted in profound microbial compositional changes including a significant enrichment of <i>Lactobacillus</i>, <i>Bifidobacterium</i>, and <i>Turicibacter</i>. Functional profiling of the fecal metagenomes revealed a markedly higher abundance of carbohydrate-active enzymes (CAZymes) in UT1-gavaged mice. Accordingly, UT1-conditioned microbiota possessed the elevated capability of utilizing starch <i>in vitro</i> and exhibited a lower availability of microbiota-accessible carbohydrates in the gut. Further analysis uncovered a functional network wherein UT1 reduced the abundance of mucin-degrading CAZymes and microbes, which correlated with a concomitant reduction of fecal mucin glycans. Collectively, our results reveal a crucial role of UT1 in facilitating the carbohydrate metabolism of the gut microbiome and expand our understanding of the genetic and phenotypic diversity of <i>F. prausnitzii</i>.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2455503"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004535","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}
引用次数: 0
Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia.
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-02-26 DOI: 10.1080/19490976.2025.2471015
Andi Chen, Chengqian Teng, Jianjie Wei, Xuyang Wu, Honghong Zhang, Pinzhong Chen, Dingliang Cai, Haitao Qian, Hui Zhu, Xiaochun Zheng, Xiaohui Chen
{"title":"Gut microbial dysbiosis exacerbates long-term cognitive impairments by promoting intestinal dysfunction and neuroinflammation following neonatal hypoxia-ischemia.","authors":"Andi Chen, Chengqian Teng, Jianjie Wei, Xuyang Wu, Honghong Zhang, Pinzhong Chen, Dingliang Cai, Haitao Qian, Hui Zhu, Xiaochun Zheng, Xiaohui Chen","doi":"10.1080/19490976.2025.2471015","DOIUrl":"10.1080/19490976.2025.2471015","url":null,"abstract":"<p><p>Neonatal hypoxic-ischemic brain damage (HIBD) is considered as a major cause of long-term cognitive impairments in newborns. It has been demonstrated that gut microbiota is closely associated with the prognosis of various neurological disorders. However, the role of microbiota-gut-brain axis on cognitive function following neonatal HIBD remains elusive. In this experiment, the correlation analysis supported the involvement of gut microbial changes following hypoxic-ischemic (HI) insult in the development of long-term cognitive impairments. Subsequent experiment revealed the involvement of the intestinal dysfunction in the hippocampal neuroinflammation and synaptic injury. In causal relationship validation experiments, fecal microbiota transplantation (FMT) from cognitively normal rats could restore gut microbial composition, improve intestinal dysfunction, reduce the serum levels of lipopolysaccharides (LPS) and inflammatory mediators, and alleviate neuroinflammation, synaptic damage and cognitive impairments in neonatal HIBD recipient rats. Conversely, the FMT from neonatal HIBD rats could induce above adverse pathological changes in the normal recipient rats. Moreover, oral administration of anti-inflammatory agent dexamethasone (DEX) exhibited the potential to alleviate these detrimental effects in neonatal HIBD rats, with the efficacy being partly reliant on gut microbiota. Further experiment on the potential molecular mechanisms using RNA sequencing indicated a significant increase in the toll-like receptor 4 (TLR4) gene in the intestinal tissues of neonatal HIBD rats. Additionally, the interventions such as TLR4 inhibitor TLR4-IN-C34 administration, FMT, and oral DEX were demonstrated to modulate intestinal function by inhibiting the LPS/TLR4 signaling pathway, thereby exerting neuroprotective effects. Collectively, these findings underscore the contribution of gut microbial dysbiosis post HI insult in activating the LPS/TLR4 signaling pathway, triggering intestinal inflammation and dysfunction, exacerbating systemic inflammation, and consequently worsening synaptic and cognitive impairments in neonatal HIBD rats. Hence, rectifying gut microbial dysbiosis or regulating intestinal function may represent a promising strategy for alleviating long-term cognitive impairments in neonates affected by HIBD.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"17 1","pages":"2471015"},"PeriodicalIF":12.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500669","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}
引用次数: 0
The immune response modulated by inoculation of commensal bacteria at birth impacts the gut microbiota and prevents Salmonella colonization.
IF 12.2 1区 医学
Gut Microbes Pub Date : 2025-12-01 Epub Date: 2025-03-13 DOI: 10.1080/19490976.2025.2474151
Florent Kempf, Rosanna Drumo, Anne Marie Chaussé, Pierrette Menanteau, Tereza Kubasova, Sylvie Roche, Anne Christine Lalmanach, Rodrigo Guabiraba, Thierry Chaumeil, Guillaume Larivière-Gauthier, Ignacio Caballero-Posadas, Béatrice Laroche, Ivan Rychlík, Isabelle Virlogeux-Payant, Philippe Velge
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