Defining the role of Parasutterella, a previously uncharacterized member of the core gut microbiota

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Abstract

The genus of Parasutterella has been defined as a core component of the human and mouse gut microbiota, and has been correlated with various health outcomes. However, like most core microbes in the gastrointestinal tract (GIT), very little is known about the biology of Parasutterella and its role in intestinal ecology. In this study, Parasutterella was isolated from the mouse GIT and characterized in vitro and in vivo. Mouse, rat, and human Parasutterella isolates were all asaccharolytic and producers of succinate. The murine isolate stably colonized the mouse GIT without shifting bacterial composition. Notable changes in microbial-derived metabolites were aromatic amino acid, bilirubin, purine, and bile acid derivatives. The impacted bile acid profile was consistent with altered expression of ileal bile acid transporter genes and hepatic bile acid synthesis genes, supporting the potential role of Parasutterella in bile acid maintenance and cholesterol metabolism. The successful colonization of Parasutterella with a single environmental exposure to conventional adult mice demonstrates that it fills the ecological niche in the GIT and contributes to metabolic functionalities. This experiment provides the first indication of the role of Parasutterella in the GIT, beyond correlation, and provides insight into how it may contribute to host health.

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Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced Leptin-Resistant Mice

Amandine Everard, Vladimir Lazarevic, Muriel Derrien … (2011)

OBJECTIVE To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice. RESEARCH DESIGN AND METHODS Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a control diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models. RESULTS In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat–fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters. CONCLUSIONS We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.

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Untargeted Metabolomics Strategies—Challenges and Emerging Directions

Stacy D Sherrod, John A. McLean, Alexandra C. Schrimpe-Rutledge … (2016)

Metabolites are building blocks of cellular function. These species are involved in enzyme-catalyzed chemical reactions and are essential for cellular function. Upstream biological disruptions result in a series of metabolomic changes, and as such the metabolome holds a wealth of information that is thought to be most predictive of phenotype. Uncovering this knowledge is a work in progress. The field of metabolomics is still maturing; the community has leveraged proteomics experience when applicable and developed a range of sample preparation and instrument methodology along with myriad data processing and analysis approaches. Research focuses have now shifted toward a fundamental understanding of the biology responsible for metabolomic changes. There are several types of metabolomics experiments including both targeted and untargeted analyses. While untargeted, hypothesis generating, workflows exhibit many valuable attributes, challenges inherent to the approach remain. This Critical Insight comments on these challenges, focusing on the identification process of LC-MS based untargeted metabolomics studies – specifically in mammalian systems. Biological interpretation of metabolomics data hinges on the ability to accurately identify metabolites. The range of confidence associated with identifications that is often overlooked is reviewed, and opportunities for advancing the metabolomics field are described.

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Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease.

M A Llopis, A M Cassard-Doulcier, L Wrzosek … (2016)

There is substantial inter-individual diversity in the susceptibility of alcoholics to liver injury. Alterations of intestinal microbiota (IM) have been reported in alcoholic liver disease (ALD), but the extent to which they are merely a consequence or a cause is unknown. We aimed to demonstrate that a specific dysbiosis contributes to the development of alcoholic hepatitis (AH).