Project description:This study employed low and high-fat purified diets containing two levels of added dietary cholesterol in conventionally raised, specific-pathogen free (SPF) mice harboring a full microbial community as compared to germ-free (GF) mice raised in complete absence of gut microbes on disease outcomes. It was hypothesized that FF-diets would lead to an earlier onset of gut dysbiosis, corresponding with elevated biomarkers of NAFLD and NASH. In the present study, we aimed to dissect the role of FF diet induced gut dysbiosis in order to mechanistically identify the underlying mechanism that influences gut-liver crosstalk between specific diet-induced bacterial populations and hepatic tissue to drive NAFLD/NASH onset and progression
Project description:HIV is known to severely affect the gastrointestinal immune system, in particular compartments of immunity that regulate gut microbial composition. Furthermore, recent studies in mice have shown that dysregulation of the gut microbiome can contribute to chronic inflammation, which is a hallmark of HIV and is thought to fuel disease progression. We sought to understand whether the gut microbial community differs in HIV-infected subjects, and whether such putative differences are associated with disease progression. We found that dysbiosis in the gut mucosally-adherent bacterial community associates with markers of chronic inflammation and disease progression in HIV-infected subjects, and this dysbiosis remains in many subjects undergiong antiretroviral therapy. We used G3 PhyloChip microarrays (commercially available from Second Genome, Inc.) to profile gut bacteria in rectosigmoid biopsies from 32 subjects: 6 HIV-infected viremic untreated (VU), 18 HIV-infected subjects on highly active antiretroviral therapy (HAART), 1 HIV-infected long-term non-progressor that is untreated (LTNP), and 9 HIV-uninfected subjects (HIV-).
Project description:DNA methylation profile of mouse sperm from conventionally-raised mice and gut dysbiosis experienced mice were characterized using whole-genome bisulfite sequencing. Genome-wide DNA methylation changes between control and dysbiotic male�s sperm were highly comparable, with no change in DNAme globally or at genomic features, only 21 differentially methylated regions (DMR) were identified, which did not overlap known regulatory elements. Epididymal sperm samples were harvested from 11 weeks old inbred male mice that were experiencing gut microbiota dysbiosis for 6-week (antibiotics treated, n=5), or drink sterilized water (control, n=5).
Project description:Gut microbiota dysbiosis characterizes systemic metabolic alteration, yet its causality is debated. To address this issue, we transplanted antibiotic-free conventional wild-type mice with either dysbiotic (“obese”) or eubiotic (“lean”) gut microbiota and fed them either a NC or a 72%HFD. We report that, on NC, obese gut microbiota transplantation reduces hepatic gluconeogenesis with decreased hepatic PEPCK activity, compared to non-transplanted mice. Of note, this phenotype is blunted in conventional NOD2KO mice. By contrast, lean microbiota transplantation did not affect hepatic gluconeogenesis. In addition, obese microbiota transplantation changed both gut microbiota and microbiome of recipient mice. Interestingly, hepatic gluconeogenesis, PEPCK and G6Pase activity were reduced even once mice transplanted with the obese gut microbiota were fed a 72%HFD, together with reduced fed glycaemia and adiposity compared to non-transplanted mice. Notably, changes in gut microbiota and microbiome induced by the transplantation were still detectable on 72%HFD. Finally, we report that obese gut microbiota transplantation may impact on hepatic metabolism and even prevent HFD-increased hepatic gluconeogenesis. Our findings may provide a new vision of gut microbiota dysbiosis, useful for a better understanding of the aetiology of metabolic diseases. all livers are from NC-fed mice only.
Project description:Insect gut microbiota plays important roles in acquiring nutrition, preventing pathogens infection, immune responses, and communicating with the environment. Gut microbiota can be affected by some external factors such as foods, temperature, and antibiotics. Spodoptera frugiperda (Lepidoptera: Noctuidae) is an important destructive pest of grain crops all over the world. The function of gut microbiota in S. frugiperda remains to be investigated. In this study, we fed the S. frugiperda with the antibiotic mixture (penicillin, gentamicin, rifampicin, and streptomycin) to perturb the gut microbiota, and further examined the effect of dysbiosis in gut microbiota on the gene expression of S. frugiperda by RNA sequencing. We found the composition and diversity of the gut bacterial community were changed in S. frugiperda after antibiotics treatmen, and the expression of genes related to energy and metabolic process were affected after antibiotics exposure in S. frugiperda. Our work will help understand the role of gut microbiota in insects.
Project description:Gut microbiota and their metabolites influence host gene expression and physiological status through diverse mechanisms. Here we investigate how gut microbiota and their metabolites impact host's mRNA m6A epitranscriptome in various antibiotic-induced microbiota dysbiosis models. With multi-omics analysis, we find that the imbalance of gut microbiota can rewire host mRNA m6A epitranscriptomic profiles in brain, liver and intestine. We further explore the underlying mechanisms regulating host mRNA m6A methylome by depleting the microbiota with ampicillin. Metabolomic profiling shows that cholic acids are the main down-regulated metabolites with Firmicutes as the most significantly reduced genus in ampicillin-treated mice comparing to untreated mice. Fecal microbiota transplantations in germ-free mice and metabolites supplementations in cells verify that cholic acids are associated with host mRNA m6A epitranscriptomic rewiring. Collectively, this study employs an integrative multi-omics analysis to demonstrate the impact of gut microbiota dysbiosis on host mRNA m6A epitranscriptomic landscape via cholic acid metabolism.
Project description:HIV is known to severely affect the gastrointestinal immune system, in particular compartments of immunity that regulate gut microbial composition. Furthermore, recent studies in mice have shown that dysregulation of the gut microbiome can contribute to chronic inflammation, which is a hallmark of HIV and is thought to fuel disease progression. We sought to understand whether the gut microbial community differs in HIV-infected subjects, and whether such putative differences are associated with disease progression. We found that dysbiosis in the gut mucosally-adherent bacterial community associates with markers of chronic inflammation and disease progression in HIV-infected subjects, and this dysbiosis remains in many subjects undergiong antiretroviral therapy.