Project description:The increased consumption of various beverages has been paralleled by an epidemic of several intestinal diseases around the world, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and colorectal cancer. Mounting evidence have shown that excessive consumption of beverages increases the risk of IBD and IBS. In addition, sugar-sweeter, food additives and food ingredients were identified to play important roles in these conditions. Consuming cold beverage is common among some people, especially in the youngsters. However, whether the cold stress contribute directly to host metabolism, gut barrier and gut-brain axis is unclear. In an intestinal function disorder model induced by cold water in mice, we investigated changes in gut transit, anxiety and depression like behavior. To evaluate the effect of cold water on gut barrier, we investigate the tight junctions in the colon. In addition, we employed RNA sequencing transcriptomic analysis to identify genes potentially driving the gut injury, and in parallel, examine the gut microbiota and metabolites in the feces.In an intestinal function disorder model induced by cold water in mice, we investigated changes in gut transit, anxiety and depression like behavior. To evaluate the effect of cold water on gut barrier, we investigate the tight junctions in the colon. In addition, we employed RNA sequencing transcriptomic analysis to identify genes potentially driving the gut injury, and in parallel, examine the gut microbiota and metabolites in the feces.
Project description:Emerging research highlights the gut microbiota's critical role in modulating brain activity via the gut-brain axis. This study explores whether targeted gastrointestinal irradiation induces abscopal effects on the brain proteome, revealing microbiota-mediated neurobiological changes. Male Sinclair minipigs were randomized to receive either sham treatment (n=6) or 8 Gy lower hemibody (gut-targeted) irradiation (n=5). Over 14 days, rectal swabs were collected to monitor microbiota dynamics, followed by frontal cortex proteomic analysis. Irradiation altered gut microbiota composition, notably reducing Chlamydiae and Firmicutes phyla, while increasing Coriobacteriaceae and Acinetobacter. Proteomic analysis identified 75 differentially abundant proteins in the frontal cortex, including a significant decrease in pannexin-1 (PANX1), suggesting modulation of the NLRP3 inflammasome pathway. Functional enrichment analysis revealed immune and neurotransmission-related changes linked to microbial shifts. These results demonstrate that gut-targeted radiation can remotely affect brain protein expression, emphasizing the microbiota's role in neuroimmune regulation and pointing to novel therapeutic opportunities in gut-brain axis disorders.
Project description:<p>The gut-brain axis facilitates two-way communication between gut inflammation and psychiatric comorbidities associated with inflammatory bowel disease (IBD). In this study, we examined the neuroprotective effects of the neuropeptide substance P (SP) on colitis. Taking into account the interactions between the intestinal microbiota and host metabolism, along with the influence of microbiota-derived metabolites on gut-brain signaling, we conducted an untargeted metabolomic analysis.</p>
Project description:Hypoxic ischemic brain damage (HIBD) is the primary cause of neurological deficits in neonates, leading to long-term cognitive impairment. Recent studies have demonstrated that gut microbiota plays a crucial role in the development of cognitive impairment after brain injury, known as the microbiota-gut-brain axis.
Project description:Approximately 80% of patients with Primary Sclerosing Cholangitis (PSC) also have an underlying Inflammatory Bowel Disease (IBD). Notably, PSC-IBD presents a unique phenotype compared to Ulcerative Colitis or Crohn’s Disease alone , which may increase the risk of colitis-associated neoplasia. This case-control study comprises a cohort of 15 patients in the PSC-IBD group, 30 patients in the IBD-alone group, and 19 patients in the control group. Through the analysis of patient serum and colon tissue proteomics, colon gene expression, fecal gut microbiota, and in vitro data with human monocytes, we identified a specific interplay between systemic circulation and gut microbiota dysbiosis that may predispose PSC-IBD patients to neoplasia development. Our study revealed that PSC-IBD patients show a shift in gut microbiota towards an increase in Intestinibacter, a bacterium known to exacerbate IBD conditions.Interestingly, when comparing the PSC-IBD group to the IBD-alone group, we observed elevated miR-21 expression levels in fasting serum and stool samples. Finally, we partially reproduce the inflammatory PSC-IBD profile using miR-21 and bile acid GCDCA stimulus in human-derived monocytes. Our findings suggest that circulating miR-21, along with bile acid GCDCA, tissue macrophage recruitment, and distinct microbiota profiles, may contribute to the unique phenotype of IBD in PSC patients.
Project description:Gut dysbiosis is closely involved in the pathogenesis of inflammatory bowel disease (IBD). However, it remains unclear whether IBD-associated gut dysbiosis plays a primary role in disease manifestation or is merely secondary to intestinal inflammation. Here, we established a humanized gnotobiotic (hGB) mouse system to assess the functional role of gut dysbiosis associated with two types of IBD - Crohn's disease (CD) and ulcerative colitis (UC). In order to explore the functional impact of dysbiotic microbiota in IBD patients on host immune responses, we analyzed gene expression profiles in colonic mucosa of hGB mice colonized with healty (HC), CD, and UC microbiota.
Project description:Brain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Towards this goal, we explored the contribution of the gut microbiome to BrM development by using in vivo breast-BrM models under germ-free conditions or antibiotic treatment. This revealed a detrimental role of gut microbiota in fostering BrM initiation. We thus evaluated the impact of antibiotics and BrM outgrowth on the gut-brain axis. We found the bacterial genus Alistipes was differentially present under antibiotic treatment and BrM progression. In parallel, we quantified circulating metabolites, revealing kynurenic acid as a differentially abundant molecule which impaired the interaction between cancer cells and the brain vasculature in ex vivo functional assays. Together, these results illuminate the potential role of gut microbiota in modulating breast-BrM via the gut-to-brain axis.