Project description:Within the human gut reside diverse microbes coexisting with the host in a mutually advantageous relationship. We comprehensively identified the modulatory effects of phylogenetically diverse human gut microbes on the murine intestinal transcriptome. Gene-expression profiles were generated from the whole-tissue intestinal RNA of mice colonized with various single microbial strains. The selection of microbe-specific effects, from the transcriptional response, yielded only a small number of transcripts, indicating that symbiotic microbes have only limited effects on the gut transcriptome overall. Moreover, none of these microbe-specific transcripts was uniformly induced by all microbes. Interestingly, these responsive transcripts were induced by some microbes but repressed by others, suggesting different microbes can have diametrically opposed consequences.
Project description:Gut-resident microbes contribute to host health via multiple mechanisms. Some of the most striking gut microbiota induced effects occur in the extraintestinal tissues and are restricted to early life. The mechanisms by which gut residing bacteria induce effects on distant host tissues and why this is restricted to a period in early life are largely unknown. We found that a subset of live gut-resident bacteria spontaneously translocate from gut to extraintestinal tissues in preweaning, but not adult mice. Translocation in preweaning mice appeared physiologic as it did not induce an inflammatory response and was in part controlled by sphingosine-1-phsophate receptor (S1PR) expressing host cells and host goblet cells. One translocating strain, Lactobacillus animalisWU, contained unique coding sequences for genes in the tyrocidine-gramicidin antibiotic-synthesizing gene cluster as well as five other regions putatively producing secondary metabolites with anti-microbial activity. Lactobacillus animalisWU exhibited antimicrobial activity against the late-onset sepsis pathogen E. coli ST69 in vitro, and translocation of L. animalisWU protected preweaning mice from systemic E. coli ST69 sepsis in vivo. These observations demonstrate a previously unappreciated higher-level symbiosis with our gut microbes.
Project description:Intestinal microbiota dysbiosis is related to many metabolic diseases in human health. Meanwhile, as an irregular environmental light-dark cycle, short-day (SD) may induce host circadian rhythms disturbances and worsen the risks of gut dysbiosis. Herein, we investigated how LD cycles regulate intestinal metabolism upon the destruction of gut microbes with antibiotic treatments. The transcriptome data indicated that SD have some negative effects on hepatic metabolism, endocrine, digestive, and diseases processes compared with normal light-dark cycle (NLD).The SD induced epithelial and hepatic purine metabolism pathway imbalance in ABX mice, the gut microbes, and their metabolites, all of which could contribute to host metabolism and digestion, endocrine system disorders, and may even cause diseases in the host.
Project description:Opioids such as morphine have many beneficial properties as analgesics, however, opioids may induce multiple adverse gastrointestinal symptoms. We have recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. However, it is unclear how opioids modulate the gut homeostasis. By using a mouse model of morphine treatment, we studied effects of morphine treatment on gut microbiome. We characterized phylogenetic profiles of gut microbes, and found a significant shift in the gut microbiome and increase of pathogenic bacteria following morphine treatment when compared to placebo. In the present study, wild type mice (C57BL/6J) were implanted with placebo, morphine pellets subcutaneously. Fecal matter were taken for bacterial 16s rDNA sequencing analysis at day 3 post treatment. A scatter plot based on an unweighted UniFrac distance matrics obtained from the sequences at OTU level with 97% similarity showed a distinct clustering of the community composition between the morphine and placebo treated groups. By using the chao1 index to evaluate alpha diversity (that is diversity within a group) and using unweighted UniFrac distance to evaluate beta diversity (that is diversity between groups, comparing microbial community based on compositional structures), we found that morphine treatment results in a significant decrease in alpha diversity and shift in fecal microbiome at day 3 post treatment compared to placebo treatment. Taxonomical analysis showed that morphine treatment results in a significant increase of potential pathogenic bacteria. Our study shed light on effects of morphine on the gut microbiome, and its role in the gut homeostasis.
Project description:We report the application of bulk RNA-sequencing-based technology for high-throughput profiling to examine the individual and combinatorial effects of the liver circadian clock and gut microbes on the liver transcriptome over 24-hours. Principle Component Analysis demonstrated that functionality of the liver circadian clock is the primary driver of the hepatic transcriptome profile, and presence of microbes is the secondary driver. We identified a range of significantly oscillating transcripts within each experimental group using empirical_JTK_CYCLE, and revealed an overall increase in oscillating transcripts with both the loss of cuntional liver clock and gut microbes. Network analysis via Spearman correlation revealed that a broken liver clock results in increased connections and correlated transcripts only in the presence of gut microbes. Finally, we show by differential expression and gene set enrichment analysis that several key metabolic pathways, particularly carbohydrate and lipid metabolism, were significantly downregulated when the liver clock is broken, regardless of microbial status. This study demonstrates the complex contributions of the liver circadian clock and gut microbes in transcriptome programming, both over time and overall.
Project description:Our work showed decreased hepatic levels of TDCA in the C26 model of cancer cachexia. We also found gut microbiota composition alterations in cachectic C26 mice, as well as reductions in microbial 7α-dehydroxylase activity, and activity of 7α-HSDH and 12α-HSDH, which drive the production of secondary bile acids. Finally, we showed that TDCA administration induces lower hepatic levels of cholesterol in C26 mice. Published in Thibaut et al, Gut Microbes 2025
2024-10-02 | GSE265876 | GEO
Project description:Gut microbes in depressed mice