[Frontier Leaders] Understanding complex glycan utilization in the human microbiota

Frontier Leaders Seminar

Title: Understanding complex glycan utilization in the human microbiota

Speaker: Harry John Gilbert

Affiliation: Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne, UK

Abstract:

The human large bowel is colonized by a community of microbes, the microbiota, which has a significant impact on human health and nutrition through the production of short chain fatty acids (SCFAs), and by interaction with the host immune system. The major nutrients available to these organisms are dietary glycans, also known as complex carbohydrates. Thus, dietary and nutraceutical strategies, based on complex carbohydrates, can, potentially, be deployed to encourage the dominance of beneficial microbes in the microbiota, particularly those producing health promoting SCFAs such as propionate and butyrate, and bacteria that have an anti-inflammatory impact through its interaction with the human immune system, ensuring that this microbial ecosystem has a positive influence on human health. This approach, however, is greatly restricted by a critical lack of understanding of the mechanisms by which complex glycans are metabolized by the microbiota. Significantly, the wealth of genomic and metagenomic microbiota sequence presents an exciting, but so far unfulfilled, opportunity to make decisive advances in our understanding of glycan metabolism in the human large bowel. This seminar will review our biochemical, genetic and microbiological strategies, in harness with metagenomic and genomic data, to understand the mechanisms of complex glycans utilization by the human microbiota. The models established1-3, will trigger the development of novel dietary strategies that are designed to maximize human health through manipulation of microbiota structure.

References:

1. Cuskin F, et al. (2015) Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism. Nature 517(7533):165-169.
2. Ndeh D, et al. (2017) Complex pectin metabolism by gut bacteria reveals novel catalytic functions. Nature 544(7648):65-70.
3. Rogowski A, et al. (2015) Glycan complexity dictates microbial resource allocation in the large intestine. Nat Commun 6:7481.

Short Biography:

After doing a B.Sc (1972-5) in Physiology and Biochemistry and PhD (1975-1979) in Biochemistry at the University of Southampton Harry Gilbert (HJG) worked for five years at the Centre for Applied and Microbiological Research, which focussed on producing products for the health service. In 1985 HJG took up a lectureship at Newcastle University becoming a full professor in 1991. Apart from working in the USA at the Centre for Complex Carbohydrate Research, University of Georgia, HJG has remained at Newcastle. In 2016 HJG was elected a Fellow of the Royal Society and a Fellow of the Medical Academy of Sciences. Since coming to Newcastle HJG has been studying the mechanisms by which enzymes, primarily glycoside hydrolases, metabolise complex carbohydrates in a variety of environments including soil and the gastrointestinal tract of herbivores and humans. He is interested in the mechanisms by which these enzymes display exquisite substrate specificity and cleave glycosidic bonds. In the last few years HJG has been exploring the mechanisms by which Bacteroides members of the human gut microbiota utilize glycans. These studies have analysed both the mechanism of glycan depolymerisation and the microbial ecology of the process. Within a medical context these bacteria, by generating fermentable monosaccharides, play an important role in shaping the structure of the human large bowel microbial community, which has a significant impact on human health. Understanding the mechanisms by which these enzymes deconstruct dietary and host glycans is critical for developing dietary strategies that maximise the beneficial impact of the microbiota, while preventing microbial dysbiosis, which can lead to serious diseases of the gastrointestinal tract.