Unravelling the determinants of resistant starch utilization by human gut microorganisms

Seminar Details
Wednesday, March 1, 2017 - 9:00am to 10:00am


Darrell Cockburn, Ph.D.
Postdoctoral Fellow - Koropatkin Lab


5623 Med. Sci. II  (Wheeler Seminar Room)

The gut microbiome can have numerous effects throughout the body. These effects are largely mediated through small molecules, such as the short chain fatty acids (SCFA) that are the end product of carbohydrate fermentation in the gut. Of the SCFA, butyrate is regarded as the most beneficial, serving as the primary energy source of colonocytes and exhibiting anti-inflammatory, anti-diabetic and anti-tumorigenic effects. Prebiotic intake can lead to increased butyrate levels and in particular the dietary fiber resistant starch is known to be highly butyrogenic. However, little is known about how resistant starch, which cannot be broken down by human enzymes, is processed by the gut microbiota.

 Eubacterium rectale is an important butyrate producing organism in the gut. It is able to grow on regular starch, but not resistant starch. In contrast Ruminococcus bromii is known to be able to grow on resistant starch, but is not a butyrate producing organism. To unravel the factors that allow resistant starch utilization, a comparison between these two organisms has been undertaken. E. rectale uses a simple system for degrading starch, relying on a single extracellular enzyme and a suite of transporters to effect growth on starch. Structural and binding analysis of the carbohydrate binding modules of this protein demonstrate that they are unable to target resistant starch, providing one reason why this organism cannot utilize that substrate. In contrast R. bromii utilizes a comparatively complex enzyme system that forms a cellulosome-like multi-enzyme complex we call the amylosome. This system allows the combining of enzymatic activities into a single molecule for the efficient attack of its substrate. As part of this system, R. bromii encodes a suite of pullulanases that can target the branch points in starch, a potential weak point in the otherwise recalcitrant resistant starch. Biochemical and structural analysis of these debranching enzymes has revealed subtly different specificities that may allow the targeting of a variety of starches, including resistant starch. Together these results allow us to begin to form a model for how resistant starch is used by the gut microbiota. 

Sponsored by the Host Microbiome Initiative