Microbial degradation of complex carbohydrates in the human distal gut
The dense consortium of microbes (microbiota) that inhabits the human distal gut makes essential contributions to our health by assisting in the digestion of complex carbohydrates. My laboratory employs a powerful combination of genomic, molecular genetic and biochemical techniques to investigate the mechanisms by which microbiota bacteria recognize and degrade the myriad of complex glycans that constantly inundate our distal gut. These glycans not only emanate from our diet, but also from our intestinal mucosa and the surfaces of other microbes inhabiting our digestive tract. Using in vivo models like gnotobiotic mice, our research seeks to provide a deeper understanding of the microbiota's impact on digestive health and will also yield mechanistic insights into how our diet influences the composition and physiology of this key 'microbial organ'. This knowledge should yield new strategies to manipulate microbiota physiology for nutritional goals and possibly ameliorate diseases such as Crohn's disease and ulcerative colitis, which are thought to result from imbalances in microbiota community structure.
Bacteroidetes Sus-like systems - A central focus in the lab is to investigate how representatives of one of the two predominant human gut bacterial phyla, the Bacteroidetes, metabolize complex glycans. These species, such as the prototypic gut symbiont Bacteroides thetaiotaomicron, have permuted and diversified a series of multi-protein cell envelope systems called 'Sus-like systems' that allow them to specifically bind and degrade nearly all of the complex glycan classes found in plant and animal cells. Moreover, members of the Bacteroidetes phylum are found in many other terrestrial and aquatic environments and these non-gut species-many of which degrade highly insoluble substrates such as chitin and cellulose-also produce Sus-like systems. We are interested in exploring the substrate range, regulation and specificity of select Sus-like systems that target complex carbohydrates of either nutritional or industrial value. The results will shed light in our greater quest to understand carbohydrate metabolism by the microbes that dwell within us, as well as those that participate in the global carbon cycle in the biosphere around us.
Koropatkin N. M., Cameron E. A., and E. C. Martens. 2012. How glycan metabolism shapes the human gut microbiota. Nature Reviews Microbiology 10: 323-35.
Martens E. C., Lowe E. C., Chiang H., Pudlo N. A., Wu M., McNulty N. P., Abbott D. W., Henrissat B., Gilbert H. J., Bolam D. N., Gordon J. I. 2011. >Recognition and degradation of plant cell wall polysaccharides by two human gut symbionts. PLoS Biology 9: e1001221.
Benjdia A, Martens E. C., Gordon J.I., Berteau O. 2011. Sulfatases and a radical S-adenosyl-L-methionine (AdoMet) enzyme are key for mucosal foraging and fitness of the prominent human gut symbiont, Bacteroides thetaiotaomicron. Journal of Biological Chemistry. 286: 25973-82.
Martens, E. C., N. M. Koropatkin, T. J. Smith, and J. I. Gordon. 2009. Complex glycan catabolism by the human gut microbiota: The Bacteroidetes Sus-like paradigm. Journal of Biological Chemistry 284: 24673-7.
Martens, E. C., R. Roth, J. E. Heuser, and J. I. Gordon. 2009. Coordinate regulation of glycan degradation and polysaccharide capsule biosynthesis by a prominent human gut symbiont. Journal of Biological Chemistry 284: 18445-18457.
Koropatkin, N. M., E. C. Martens, J. I. Gordon, and T. Smith. 2009. The structure of a SusD homolog involved in mucin O-glycan utilization in a prominent human gut symbiont. Biochemistry 48: 1532-42.
Martens, E. C., H. Chiang, and J. I. Gordon. 2008. Mucosal glycan foraging enhances persistence and transmission by a human gut symbiont. Cell Host and Microbe 4: 447-457.
Koropatkin, N. M., E. C. Martens, J. I. Gordon, and T. Smith. 2008. Starch catabolism by a prominent human gut symbiont is directed by the recognition of amylose helices. Structure 16: 1-11.