Author
CUSKIN, FIONA - Newcastle University | |
LOWE, ELISABETH - Newcastle University | |
TEMPLE, MAX - Newcastle University | |
ZHU, YANPING - Newcastle University | |
CAMERON, ELIZABETH - University Of Michigan Medical School | |
PUDLO, NICHOLAS - University Of Michigan Medical School | |
PORTER, NATHAN - University Of Michigan Medical School | |
URS, KARTHIK - University Of Michigan Medical School | |
THOMPSON, ANDREW - University Of York | |
CARTMELL, ALAN - University Of Melbourne | |
ROGOWSKI, ARTHUR - Newcastle University | |
HAMILTON, BRIAN - Indiana University | |
CHEN, RUI - Indiana University | |
TOLBERT, THOMAS - University Of Kansas Medical School | |
PIENS, KATHLEEN - Oxyrane | |
BRACKE, DEBBY - Oxyrane | |
VERVECKEN, WOUTER - Oxyrane | |
HAKKI, ZALIHE - University Of Melbourne | |
SPECIALE, GAETANO - Melbourne University | |
MUNOZ-MUNOZ, JOSE - Newcastle University | |
DAY, ANDREW - Newcastle University | |
PENA, MARIA - University Of Georgia | |
MCLEAN, RICHARD - Agriculture And Agri-Food Canada | |
SUITS, MICHAEL - University Of Victoria | |
BORASTON, ALISDAIR - University Of Victoria | |
Atherly, Todd | |
Ziemer, Cherie | |
WILLIAMS, SPENCER - University Of Melbourne | |
DAVIES, GIDEON - University Of York | |
ABBOTT, WADE - University Of Georgia | |
MARTENS, ERIC - University Of Michigan Medical School | |
GILBERT, HARRY - Newcastle University |
Submitted to: Nature
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 5/25/2014 Publication Date: 1/8/2015 Citation: Cuskin, F., Lowe, E., Temple, M., Zhu, Y., Cameron, E.A., Pudlo, N., Porter, N.T., Urs, K., Thompson, A., Cartmell, A., Rogowski, A., Hamilton, B.S., Chen, R., Tolbert, T., Piens, K., Bracke, D., Vervecken, W., Hakki, Z., Speciale, G., Munoz-Munoz, J., Day, A., Pena, M., McLean, R., Suits, M., Boraston, A., Atherly, T.A., Ziemer, C.J., Williams, S., Davies, G., Abbott, W., Martens, E., Gilbert, H. 2015. Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism. Nature. 517:165-169. DOI: 10.1038/nature13995. Interpretive Summary: The human diet contains many complex carbohydrates which cannot be utilized without enzymes produced by gut microbes. Yeasts and other fungi have some complex carbohydrates such as mannan which are not found in plants. Yeasts are some of the earliest 'domesticated' microbes and have been part of the human diet for at least 7000 years. The gut bacterium Bacteroides thetaioataomicron, a predominant gut microbe, contains a number of genes capable of degrading mannan; these genes are not found in many gut bacteria. These data support a 'selfish' model of carbohydrate utilization, as apposed to a 'sharing' model, a currently held hypothesis which suggests extensive synergy amongst gut bacteria for utilization of complex carbohydrates. Bacteroides thetaiotaomicron has evolved the specific and somewhat unique ability to utilize yeast carbohydrates. This demonstrates an important linkage between gut microbes and human nutrition as well as adaptive gut bacterial evolution in response to human dietary changes. Both humans and animals will beneift from the understanding gained from studying these intestinal bacteria and their effects in health and disease. Technical Abstract: The architecture of the human distal gut microbiota (microbiota) is sculpted by the complex carbohydrates delivered in the diet. Yeasts, which are among the earliest domesticated microorganisms and have been a component of the human diet for at least 7000 years, possess an elaborate cell wall alpha-mannan. The influence of yeast mannan on the ecology of the microbiota, however, is unknown. Significantly, Bacteroides thetaiotaomicron (Bt), a dominant and widespread member of the human large bowel microbial community, has a genome that encodes an extensive repertoire of enzymes capable of hydrolyzing alpha-mannosidic linkages. We show here using transcriptional analysis, enzyme specificity, cellular localization, structural biology, chromosomal modifications and gnotobiotic mouse experiments that yeast alpha-mannan is a viable food source for Bt. Furthermore, distinct polysaccharide utilization loci (PULs) orchestrate the differential degradation of yeast alpha-mannan and high mannose mammalian N-glycans (HMNGs) in spite of their structural similarities. We propose a model whereby limited cleavage of the alpha-mannan backbone by surface endo-alpha1,6-mannanases generates large oligosaccharides that are depolymerized to mannose by the synergistic action of an array of specific periplasmic exo- and endo-acting glycoside hydrolases and phosphatases. The metabolism of yeast mannan by Bt supports a 'selfish' model for polysaccharide catabolism at odds with the 'nutrient sharing' hypothesis that suggests extensive synergy between members of the microbiota in the utilization of complex carbohydrates. This report shows how a cohort of highly successful members of the microbiota have evolved to consume sterically-restricted glycans presented on the surface of yeasts, an adaptation to the domestication of yeast and its increasing impact on the civilized human diet. |