Colonic metaproteomic signatures of active bacteria and the host in obesity

Abstract

Obesity is associated with the intestinal microbiota in humans but the underlying mechanisms are yet to be fully understood. Our previous phylogenetic study showed that the faecal microbiota profiles of nonobese versus obese and morbidly obese individuals differed. Here, we have extended this analysis with a characterization of the faecal metaproteome, in order to detect differences at a functional level. Proteins were extracted from crude faecal samples of 29 subjects, separated by 1D gel electrophoresis and characterized using RP LC-MS/MS. The peptide data were analyzed in database searches with two complementary algorithms, OMSSA and X!Tandem, to increase the number of identifications. Evolutionary genealogy of genes: nonsupervised orthologous groups (EggNOG) database searches resulted in the functional annotation of over 90% of the identified microbial and human proteins. Based on both bacterial and human proteins, a clear clustering of obese and nonobese samples was obtained that exceeded the phylogenetic separation in dimension. Moreover, integration of the metaproteomics and phylogenetic datasets revealed notably that the phylum Bacteroidetes was metabolically more active in the obese than nonobese subjects. Finally, significant correlations between clinical measurements and bacterial gene functions were identified. This study emphasizes the importance of integrating data of the host and microbiota to understand their interactions.

Microbiome and metabolic disease: revisiting the bacterial phylum Bacteroidetes

“…Members of the Bacteroidetes appear to be metabolically highly flexible. A recent proteomics analysis of obese and lean human gut microbiomes has highlighted that Bacteroidetes are more metabolically active in obese microbiomes despite their lower abundances [21]. Metabolic flexibility was demonstrated in a mouse model system by Sonnenburg and colleagues, who showed that when B. thetaiotaomicron was mono-associated with germfree mice, it exhibited a clear preference for certain substrates over others, and would alter gene expression to match changing substrate availability in its environment [22].…”

Intestinal microbiome landscaping: insight in community assemblage and implications for microbial modulation strategies

“…2012; Kolmeder et al . 2012, 2015). Metatranscriptomics analysis of fecal samples from 10 American adults revealed alterations in gene-expression profiles after changes in dietary intake (David et al .…”

“…Similarly, metaproteomic comparison of 29 non-obese and obese adults has shown larger differences in the active functional bacteria between the two groups than those observed at the compositional level (Kolmeder et al . 2015). While these studies are a step toward functional understanding of the human microbiome, the field is still young.…”

Gut microbiome and lipid metabolism

“…The study of Maurice et al [58] linked bacterial composition, activity, and expression to identify the active component of the gut microbiomta responding to xenobiotics. A recent metaproteomics study compared the level of bacterial proteins between obese and nonobese samples and identified the phylum Bacteroidetes was metabolically more active in the obese than nonobese samples [59]. These proof-of-concept studies demonstrate the power of a systems microbiology study in understanding function and dynamics of gut ecosystems and their role in the development of diseases.…”