Project description:β-Mannans are plant cell wall polysaccharides that are commonly found in human diets. However, a mechanistic understanding into the key populations that degrade this glycan is absent, especially for the dominant Firmicutes phylum. Here, we show that the prominent butyrate-producing Firmicute Roseburia intestinalis expresses two loci conferring metabolism of β-mannans. We combine multi-“omic” analyses and detailed biochemical studies to comprehensively characterize loci-encoded proteins that are involved in β-mannan capturing, importation, de-branching and degradation into monosaccharides. In mixed cultures, R. intestinalis shares the available β-mannan with Bacteroides ovatus, demonstrating that the apparatus allows coexistence in a competitive environment. In murine experiments, β-mannan selectively promotes beneficial gut bacteria, exemplified by increased R. intestinalis, and reduction of mucus-degraders. Our findings highlight that R. intestinalis is a primary degrader of this dietary fiber and that this metabolic capacity could be exploited to selectively promote key members of the healthy microbiota using β-mannan-based therapeutic interventions.
2019-02-21 | PXD012448 | Pride
Project description:Xylan utilization by Roseburia intestinalis
Project description:The polysaccharide β-mannan, which is common in terrestrial plants but unknown in microalgae, was recently detected during diatom blooms. We identified a β-mannan polysaccharide utilization locus (PUL) in the genome of the marine Flavobacterium Muricauda sp. MAR_2010_75 which resembles PULs in bacteria from diverse ecosystems. Proteomics showed the β-mannan induced translation of 22 proteins encoded within the PUL.
Project description:The aim of this RNA-sequencing study is to measure differential gene expression in 4 intestinal bacteria (Bacteroides xylanisolvens, Bacteroides thetaiotaomicron, Subdoligranulum variabile and Roseburia intestinalis). The data highlight the coordinated action of genes within the same locus involved in the degradation of complex carbohydrates. These loci are well characterized in Bacteroidetes species and referred to as polysaccharide utilization loci. In Firmicutes species, these loci are not so clear-cut, athough the GP-PUL concept has already been proposed. Here we compare the differential gene expression in minimal culture medium supplemented with a complex carbohydrate with a minimal culture medium supplemented with glucose. This differential analysis reveals a source-specific genetic response and a coordinated expression of genes involved in carbohydrate transport, carbohydrate degradation and transcriptional activation of these complex enzymatic machineries.
Project description:Background: Humans with metabolic and inflammatory diseases frequently harbor lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Results: We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary components to (i) impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization, (ii) improve intestinal barrier function, (iii) lower systemic inflammation and (iv) ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate improves gut barrier function and reduces atherosclerosis development. Conclusions: Altogether, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis.
Project description:Beneficial modulation of the gut microbiome has high-impact implications not only in humans, but also in livestock that sustain our current societal needs. In this context, we have engineered an acetylated galactoglucomannan (AcGGM) fibre from spruce trees to match unique enzymatic capabilities of Roseburia and Faecalibacterium species, both renowned butyrate-producing gut commensals. The accuracy of AcGGM was tested in an applied pig feeding trial, which resolved 355 metagenome-assembled genomes together with quantitative metaproteomes. In AcGGM-fed pigs, both target populations differentially expressed AcGGM-specific polysaccharide utilization loci, including novel, mannan-specific esterases that are critical to its deconstruction. We additionally observed a “butterfly effect”, whereby numerous metabolic changes and interdependent cross-feeding pathways were detected in neighboring non-mannolytic populations that produce short-chain fatty acids. Our findings show that intricate structural features and acetylation patterns of dietary fibre can be customized to specific bacterial populations, with the possibility to create greater modulatory effects at large.