Metaproteomics of mouse gut microbiomes under different kinds of obesity and morphine treatment
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ABSTRACT:
INSTRUMENT(S): Q Exactive Plus
ORGANISM(S): Mouse Gut Microbiome
SUBMITTER: 
Robert L. Hettich
PROVIDER: MSV000085110 | MassIVE | Tue Mar 17 11:35:00 GMT 2020
SECONDARY ACCESSION(S): PXD018195
REPOSITORIES: MassIVE
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Project description:This dataset contains proteomic data from mice with high or low weight gain in response to a high fat diet. Both host and microbial proteins are present. In the supplemental, there are also tables and supplementary files that can be used for replicating the bioinformatic analysis.
Abstract:
Consumption of refined high-fat, low-fiber diets promotes development of obesity and its associated consequences. While genetics play an important role in dictating susceptibility to such obesogenic diets, mice with nearly uniform genetics exhibit marked heterogeneity in their extent of obesity in response to such diets. This suggests non-genetic determinants play a role in diet-induced obesity. Hence, we sought to identify parameters that predict, and/or correlate with, development of obesity in response to an obesogenic diet. We assayed behavior, metabolic parameters, inflammatory markers/cytokines, microbiota composition, and the fecal metaproteome, in a cohort of mice (n=50) prior to, and the 8 weeks following, administration of an obesogenic high-fat low-fiber diet. Neither behavioral testing nor quantitation of inflammatory markers broadly predicted severity of diet-induced obesity. Although, the small subset of mice that exhibited basal elevations in serum IL-6 (n=5) were among the more obese mice in the cohort. While fecal microbiota composition changed markedly in response to the obesogenic diet, it lacked the ability to predict which mice were relative prone or resistant to obesity. In contrast, fecal metaproteome analysis revealed functional and taxonomic differences among the proteins associated with proneness to obesity. Targeted interrogation of microbiota composition data successfully validated the taxonomic differences seen in the metaproteome. While future work will be needed to determine the breadth of applicability of these associations to other cohorts of animals and humans, this study nonetheless highlights the potential power of gut microbial proteins to predict and perhaps impact development of obesity.
2019-06-04 | MSV000083891 | MassIVE
Project description:Aims Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of the metabolic syndrome (MetS). Lifestyle-induced weight loss (WL) is regarded as an efficient therapy to reverse MetS and to prevent disease progression. The objective of this study was to investigate if lifestyle-induced WL modulates the gut microbiome and its interaction with the host. Methods We analyzed and compared the fecal metaproteome of 33 individuals with MetS in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort (ICTRP Trial Number: U1111-1158-3672). Results The 6-month WL intervention resulted in reduced BMI (-13.9%), increased insulin sensitivity (HOMA-IR; -53.70%) and reduced levels of circulating CRP (-66.86%), indicating MetS reversal. The metaprotein spectra of the host revealed a decrease of human proteins associated with gut inflammation and reduced abundance of human pancreatic alpha-amylase. Surprisingly, taxonomic analysis of the fecal metaproteome revealed only minor changes in the bacterial composition with an increase of low-abundant families (Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae, Verrucomicrobiaceae). Yet, we detected increased abundance of microbial metaprotein spectra that correspond to enhanced hydrolysis of complex carbohydrates (endoglucanase A, β-1,4-mannooligosaccharide phosphorylase, galactokinase, 5-keto-D-gluconate 5-reductase), indicating functional changes of the gut microbiome. Conclusions Our results indicate that lifestyle induced WL may improve interaction between the gut microbiome and the host in individuals with MetS, while bacterial composition remained almost stable. Metaproteome analysis of host proteins reveals reduced gut inflammation whereas microbial metaprotein spectra indicate functional changes towards degradation of complex carbohydrates. The filenames correspond to the ID of the patient (1-33), whereas “C” corresponds to baseline and “ABC” to weight loss.
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Project description:The increasing prevalence of obesity and related metabolic disorders represents a growing public health concern. Despite advances in other areas of medicine, a safe and effective drug treatment for obesity has been elusive. Obesity has repeatedly been linked to reorganization of the gut microbiome 1-4 , yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here we show that gut microbe-targeted inhibition of the metaorganismal trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (ob/ob). Selective small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not significantly reduce food intake, but instead is associated with beneficial remodeling of the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. Leveraging untargeted metabolomics we discovered that CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. Collectively, this study underscores the close relationship between microbe and host metabolism, and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors can have profound effects on host energy metabolism, and have untapped potential as anti-obesity therapeutics.
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