Project description:Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber guar gum and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, guar gum enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to guar gum, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither guar gum or antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.
Project description:The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans. This randomized, placebo-controlled, double-blind study had a 3-armed parallel design. Overweight/obese participants were randomized to oral intake of amoxicillin, vancomycin or placebo for 7 consecutive days. After an overnight fast, subcutaneous adipose tissue biopsies were taken that were subjected to gene expression profiling by array.
Project description:Influenza A(H1N1)pdm virus caused the first human pandemic of the 21st century. Although various probiotic Lactobacillus species have been shown to have anti-microbial effects against pneumonia-inducing pathogens, the prophylactic efficacy and mechanisms behind their protection remain largely unknown. Here, we evaluated the prophylactic efficacy of heat-killed Lactobacillus pentosus b240 against lethal influenza A(H1N1)pdm virus infection in a mouse model. To further define the protective responses induced by b240, we performed virologic, histopathologic, and transcriptomic analyses on the mouse lungs. Although we did not observe an appreciable effect of b240 on virus growth, cytokine production, or histopathology, gene expressional analysis revealed that oral administration of b240 differentially regulates antiviral gene expression in mouse lungs. Our results unveil the possible mechanisms behind the protection mediated by b240 against influenza virus infection and provide new insights into probiotic therapy. Six-week-old female BALB/c mice were used in the study. Oral administration of b240 was initiated in mice at six weeks of age. Mice were orally administered heat-killed Lactobacillus pentosus b240 every day at a dose of 10 mg/mouse in 200 μl of buffered saline for 5 weeks. The control group received saline. To investigate the effects of oral administration of b240 on host immune responses to CA04 virus infection, 9 mice per group were infected with 10 MLD50 of CA04 virus on day 21 post-b240 administration. Three mice per group were euthanized on days 1, 3, and 6 post-infection and their lungs were collected. To investigate the immune responses induced by oral administration of b240 in the lungs of uninfected mice, 15 mice per group were mock-infected with PBS on day 21 post-b240 administration. Three mice per group were euthanized on days 14, 21, 22, 24, and 27 post-b240 administration (-7, 0, 1, 3, and 6 days post-mock infection) and their lungs were collected. These lung tissues were subjected to microarray analysis (three biological replicates per each group).
Project description:Because antibiotics have been widely used to prevent severe losses due to infectious fishery diseases, the liberal application and overuse of antibiotics has led to the spread and evolution of bacterial resistance, food safety hazards, and environmental issues. The use of some antibiotics, including florfenicol and enrofloxacin, is allowed in aquaculture in China. Accordingly, to better address the concerns and questions associated with the impact of administered enrofloxacin and florfenicol to grass carp, here we investigated the immune response, bacterial diversity, and transcriptome of the intestine of C. idella treated with these oral antibiotics. The aim of this study was to provide an in-depth evaluation of the antibiotic-induced patterns and dynamics of the microbiota grass carp and the potential mechanism involved.
Project description:A study aiming to determine if mice humanized by different donors have different gut microbiota and colonic gene expression patterns in response to the administration of a commonly prescribed, broad-spectrum antibiotic (co-amoxiclav). Male, germ-free mice were humanized by one of two healthy, unrelated human donors. 56 days later, gut microbiota and colonic transcriptome samples were analyzed at baseline, by 454 pyrosequencing and Agilent microarray, respectively. Antibiotics were then administered for 7 days, following by repeated sampling of both the microbiota and colonic RNA at days 8, 11 and 18. Results of the microbiota analysis revealed marked shifts in the composition of one donor group in response to antibiotics and not the other donor group. Transcriptomics revealed a more conserved response, however the magnitude of the effect was greater in the donor group that had a greater shift in the microbiota.
Project description:Broad-spectrum antibiotics are frequently administered prophylactically to intensive care unit patients as part of empiric care. This treatment has been associated with subsequent infections by the emerging nosocomial pathogen Acinetobacter baumannii; however, the mechanisms underlying this association remain unclear. Here, we demonstrate in a murine model that prophylactic broad-spectrum antibiotic administration drives susceptibility to intranasal infections with A. baumannii, and that reconstitution of the intestinal microbiota by fecal microbiota transplant restores control of infection, implicating microbiota dysbiosis as a key driver of pulmonary disease. Using single-cell RNA sequencing, we determine that prophylaxis suppresses phagocyte effector functions in the lung, including nutritional immunity pathways that restrict pathogen access to essential nutrient metals. Depletion studies identify neutrophils and inflammatory monocytes as central mediators of microbiota-dependent protection, and infection of mice lacking nutritional immunity components lipocalin-2 or calprotectin abrogates the effects of prophylaxis, establishing a causal linkage between microbiota dysbiosis and impaired phagocyte-mediated nutritional immunity. Together, these findings provide a mechanism for the increased severity of A. baumannii pneumonia following antibiotic exposure and highlight the intestinal microbiota as a potential therapeutic target to prevent future nosocomial infections with this and other healthcare-associated pathogens.
Project description:Aim of this study is to implement the intestinal microbiota by perioperative administration of probiotics, oral antibiotics and low volume mechanical preparation in order to reduce the incidence of colorectal anastomotic leaks and dehiscences.
Project description:The use of some antibiotics, including florfenicol and enrofloxacin, is allowed in aquaculture in China. Accordingly, to better address the concerns and questions associated with the impact of administered enrofloxacin and florfenicol to grass carp, here we investigated the transcriptome of the intestine of C. idella treated with these oral antibiotics. The aim of this study was to provide an in-depth evaluation of the antibiotic-induced patterns and dynamics of the microbiota grass carp and the potential mechanism involved.
Project description:The purpose of this study is to determine optimal prophylactic antibiotics administration method in elective laparoscopic colorectal surgery.
Project description:Influenza A(H1N1)pdm virus caused the first human pandemic of the 21st century. Although various probiotic Lactobacillus species have been shown to have anti-microbial effects against pneumonia-inducing pathogens, the prophylactic efficacy and mechanisms behind their protection remain largely unknown. Here, we evaluated the prophylactic efficacy of heat-killed Lactobacillus pentosus b240 against lethal influenza A(H1N1)pdm virus infection in a mouse model. To further define the protective responses induced by b240, we performed virologic, histopathologic, and transcriptomic analyses on the mouse lungs. Although we did not observe an appreciable effect of b240 on virus growth, cytokine production, or histopathology, gene expressional analysis revealed that oral administration of b240 differentially regulates antiviral gene expression in mouse lungs. Our results unveil the possible mechanisms behind the protection mediated by b240 against influenza virus infection and provide new insights into probiotic therapy.