Project description:Type 2 diabetes (T2D), the most common form of diabetes, is one of the leading causes of death in the USA. Diet, genetics, environment, and the gut microbes are important factors causing T2D. However, the exactmechanisms by which these factors induce the disease are still unclear. Western diet-induced obesity mimicked the conditions of metabolic syndrome and T2D in mice. Concurrent changes in the bacterial abundance and composition in ileum and stool of mice indicated that the metabolic alterations are associated with microbes.Using a transkingdom network and causal inference analysis, we identified candidate microbes that can potentially mediate changes in metabolic health. In line with our predictions, supplementing mice with the beneficial microbial candidates ameliorated diet induced diabetes in mice. Transcriptomic studies showed that these microbes improved metabolic parameters by regulating mitochondrial processes in the liver. Using systems biology network analyses, followed by experimental validation, we identified key microbes and pathways regulating glucose metabolism. This research aims to uncover the mechanisms of microbiota dependent glucose metabolism to advance treatment of T2D.
Project description:Oxalate, a ubiquitous compound in many plant-based foods, is absorbed through the intestine and precipitates with calcium in the kidneys to form stones. Over 80% of diagnosed kidney stones are found to be calcium oxalate. People who form these stones often experience a high rate of recurrence and treatment options remain limited despite decades of dedicated research. Recently, the intestinal microbiome has become a new focus for novel therapies. Studies have shown that select species of Lactobacillus, the most commonly included genus in modern probiotic supplements, can degrade oxalate in vitro and even decrease urinary oxalate in animal models of Primary Hyperoxaluria. Although the purported health benefits of Lactobacillus probiotics vary significantly between species, there is supporting evidence for their potential use as probiotics for oxalate diseases. Defining the unique metabolic properties of Lactobacillus is essential to define how these bacteria interact with the host intestine and influence overall health. We addressed this need by characterizing and comparing the metabolome and lipidome of the oxalate-degrading Lactobacillus acidophilus and Lactobacillus gasseri using ultra-high-performance liquid chromatography-high resolution mass spectrometry. We report many species-specific differences in the metabolic profiles of these Lactobacillus species and discuss potential probiotic relevance and function resulting from their differential expression. Also described is our validation of the oxalate-degrading ability of Lactobacillus acidophilus and Lactobacillus gasseri, even in the presence of other preferred carbon sources, measuring in vitro 14C-oxalate consumption via liquid scintillation counting.
Project description:To survive during colonization or infection of the human body, microorganisms must defeat antimicrobial peptides, which represent a key component of innate host defense in phagocytes and on epithelia. However, is not known how the clinically important group of Gram-positive bacteria sense antimicrobial peptides to coordinate a directed defensive response. By determining the genome-wide gene regulatory response to human beta defensin 3 in the nosocomial pathogen Staphylococcus epidermidis, we discovered an antimicrobial peptide sensor system that controls major specific resistance mechanisms to antimicrobial peptides and is unrelated to the Gram-negative PhoP/PhoQ system. Wild type untreated in triplicate is compared to wild type treated in triplicate along with three mutants in triplicate with and without treatment of human beta defensin 3, totalling 30 samples