A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes

• Published in: Nature (London) Vol. 506; no. 7489; pp. 498 - 502
• Main Authors: Larsbrink, Johan, Rogers, Theresa E., Hemsworth, Glyn R., McKee, Lauren S., Tauzin, Alexandra S., Spadiut, Oliver, Klinter, Stefan, Pudlo, Nicholas A., Urs, Karthik, Koropatkin, Nicole M., Creagh, A. Louise, Haynes, Charles A., Kelly, Amelia G., Cederholm, Stefan Nilsson, Davies, Gideon J., Martens, Eric C., Brumer, Harry
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27-02-2014; Nature Publishing Group
• Subjects: 13/51; 14/63; 38/77; 42/44; 42/70; 45/29; 45/44; 45/90; 631/326/41/547; 631/45/72/1201; 631/535/1266; 64/60; 82; 82/1; 82/16; 82/58; 82/83; 96; Active Enzymes; Amino Acid Sequence; Bacteriology; Bacteroides - enzymology; Bacteroides - genetics; Bacteroides - growth & development; Bacteroides - metabolism; Biochemical analysis; Carbohydrate Metabolism - genetics; Carbohydrate Sequence; Carbohydrate-Binding Modules; Carbohydrates; Cell Wall - chemistry; Cell Walls; Chromatography; Crystallography, X-Ray; Diet; Dietary Fiber; Enzymes; Evolution, Molecular; Fermentation; Gastrointestinal Tract - microbiology; Genes; Genetic aspects; Genetic engineering; Genetic Loci - genetics; Genetic markers; Genomes; Glucans - chemistry; Glucans - metabolism; Glycoside Hydrolases - chemistry; Glycoside Hydrolases - genetics; Glycoside Hydrolases - metabolism; Human Microbiome; Humanities and Social Sciences; Humans; Intestinal Bacteria; letter; Maximum-Likelihood; Metabolism; Metagenome; Microbiota (Symbiotic organisms); Models, Molecular; Molecular Sequence Data; multidisciplinary; Phylogeny; Physiological aspects; Population ecology; Protein Structure, Tertiary; Proteins; Quantitative trait loci; Reagent; Recognition; Reducing Sugar; Saccharides; Science; Symbiosis; Xylans - chemistry; Xylans - metabolism; Xyloglucans
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature12907

A genetic locus from the gut symbiont
Bacteroides ovatus
is identified and described that encodes a cohort of enzymes and carbohydrate-binding proteins necessary for the metabolism of xyloglucans—a predominant component of dietary fibre.
Niche bacteria central to digestion of plant fibre
We can derive energy from dietary fibre thanks largely to the ability of the gut microbiota to digest and ferment complex polysaccharides. The mechanism of degradation of one ubiquitous family of branched plant cell wall polysaccharides, the xyloglucans, has been unclear. Here Harry Brumer and colleagues report the identification and molecular characterization of an archetypal genetic locus from the gut symbiont
Bacteroides ovatus
encoding enzymes dedicated to xyloglucan utilization. The ability to utilize xyloglucan is shown not to be universal among the Bacteroidetes but rather is carried out by a few specialists. The importance of a niche species of bacteria in the utilization of such an abundant form of dietary fibre is of relevance to the design of dietary strategies for the treatment of intestinal disease and highlights the need for careful strain selection and monitoring for achieving a healthy, balanced microbiota.
A well-balanced human diet includes a significant intake of non-starch polysaccharides, collectively termed ‘dietary fibre’, from the cell walls of diverse fruits and vegetables
1
. Owing to the paucity of alimentary enzymes encoded by the human genome
2
, our ability to derive energy from dietary fibre depends on the saccharification and fermentation of complex carbohydrates by the massive microbial community residing in our distal gut
3
,
4
. The xyloglucans (XyGs) are a ubiquitous family of highly branched plant cell wall polysaccharides
5
,
6
whose mechanism(s) of degradation in the human gut and consequent importance in nutrition have been unclear
1
,
7
,
8
. Here we demonstrate that a single, complex gene locus in
Bacteroides ovatus
confers XyG catabolism in this common colonic symbiont. Through targeted gene disruption, biochemical analysis of all predicted glycoside hydrolases and carbohydrate-binding proteins, and three-dimensional structural determination of the vanguard
endo
-xyloglucanase, we reveal the molecular mechanisms through which XyGs are hydrolysed to component monosaccharides for further metabolism. We also observe that orthologous XyG utilization loci (XyGULs) serve as genetic markers of XyG catabolism in Bacteroidetes, that XyGULs are restricted to a limited number of phylogenetically diverse strains, and that XyGULs are ubiquitous in surveyed human metagenomes. Our findings reveal that the metabolism of even highly abundant components of dietary fibre may be mediated by niche species, which has immediate fundamental and practical implications for gut symbiont population ecology in the context of human diet, nutrition and health
9
,
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,
11
,
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.