Abstract
Dietary fibers impact gut colonic health, through the production of short-chain fatty acids. A low-fiber diet has been linked to lower bacterial diversity, obesity, type 2 diabetes, and promotion of mucosal pathogens. Glycoside hydrolases (GHs) are important enzymes involved in the bacterial catabolism of fiber into short-chain fatty acids. However, the GH involved in glycan breakdown (adhesion, hydrolysis, and fermentation) are organized in polysaccharide utilization loci (PUL) with complex modularity. Our goal was to explore how the capacity of strains, from the Bacteroidetes phylum, to grow on fiber could be predicted from their genome sequences. We designed an in silico pipeline called FiberGrowth and independently validated it for seven different fibers, on 28 genomes from Bacteroidetes-type strains. To do so, we compared the existing GH annotation tools and built PUL models by using published growth and gene expression data. FiberGrowth’s prediction performance in terms of true positive rate (TPR) and false positive rate (FPR) strongly depended on available data and fiber: arabinoxylan (TPR: 0.89 and FPR: 0), inulin (0.95 and 0.33), heparin (0.8 and 0.22) laminarin (0.38 and 0.17), levan (0.3 and 0.06), mucus (0.13 and 0.38), and starch (0.73 and 0.41). Being able to better predict fiber breakdown by bacterial strains would help to understand their impact on human nutrition and health. Assuming further gene expression experiment along with discoveries on structural analysis, we hope computational tools like FiberGrowth will help researchers prioritize and design in vitro experiments.
Highlights
The human large intestine supports an extremely dense and diverse microbial community—up to 100 trillion individuals—known as the gut microbiota (Bäckhed et al, 2005)
The microbiome has been shown to play an important role in human health, and numerous studies have documented the link between microbiota composition and metabolic diseases, such as type 2 diabetes (T2D) (Qin et al, 2012), obesity, colorectal cancer (Thomas et al, 2019), immune response to treatment (Tanoue et al, 2019), and inflammatory bowel diseases such as Crohn’s disease
The mechanism of action being the depletion of dietary fibers—a nutrient category that includes a broad array of polysaccharides that are not digestible by human enzymes— in industrialized countries’ diet (Burkitt et al, 1972; Faith et al, 2011; Sonnenburg and Sonnenburg, 2014; Zmora et al, 2018)
Summary
The human large intestine supports an extremely dense and diverse microbial community—up to 100 trillion individuals—known as the gut microbiota (Bäckhed et al, 2005). The microbiome has been shown to play an important role in human health, and numerous studies have documented the link between microbiota composition and metabolic diseases, such as type 2 diabetes (T2D) (Qin et al, 2012), obesity, colorectal cancer (Thomas et al, 2019), immune response to treatment (Tanoue et al, 2019), and inflammatory bowel diseases such as Crohn’s disease. One of the parameters playing a part in the booming number of individuals affected by metabolic disorders is the reduction of polysaccharide diversity in the day-to-day diet. The mechanism of action being the depletion of dietary fibers—a nutrient category that includes a broad array of polysaccharides that are not digestible by human enzymes— in industrialized countries’ diet (Burkitt et al, 1972; Faith et al, 2011; Sonnenburg and Sonnenburg, 2014; Zmora et al, 2018)
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