The Chemistry of Microbiomes Proceedings of a Seminar Series (2017) / Chapter Skim
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9 Deciphering the Chemistry of the Human Gut Microbiome - Emily P. Balskus
9 Deciphering the Chemistry of the Human Gut Microbiome - Emily P. Balskus
Pages 57-64
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From page 57... ...
INTRODUCTION Trillions of microorganisms live in the human gut, making it one of the densest microbial habitats. These organisms play critical roles in host health, and a growing body of research has correlated changes in this microbial community to disease.
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From page 58... ...
ELUCIDATING THE GENETIC AND BIOCHEMICAL BASIS FOR GUT MICROBIAL METABOLISM Connecting Known Microbial Activities to Genes and Enzymes A critical step in understanding human gut microbial metabolism is linking metabolic activities with specific microbial genes and enzymes. The genes encoding the enzymes that carry out individual transformations could be robust diagnostic markers that would predict the presence of particular functions in gut multi-omics datasets of metagenomes, metatranscriptomes, and metaproteomes.
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From page 59... ...
We anticipate that "chemically guided" genome mining may be applied more generally to uncover the genes that mediate additional gut microbial metabolic activities. Connecting Genes of Unknown Function to Microbial Metabolism Another major challenge facing microbiome research is how to elucidate the functions of the vast numbers of misannotated or uncharacterized genes found in these communities.
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From page 60... ...
Notably, chemical tools routinely used in other areas of biology, including eukaryotic cell biology and studies of microbial pathogens, may be leveraged, adapted, and extended to understand the functions of microbial communities, including the human gut microbiome. Chemical Genetics and the Human Gut Microbiome Developing selective ways of manipulating gut microbial functions may hold the key not only to deciphering the contributions of individual activities to community and host health, but also to rationally altering the microbiome for therapeutic benefit.
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From page 61... ...
Although further questions remain regarding the broad effects of these inhibitors on gut microbiome composition and functions, as well as the long-term consequences of b-glucuronidase inhibition, this work provides important proof of concept for the idea of using chemical genetics to manipulate metabolism in this microbial community. As has been the case for eukaryotic cell biology and microbial pathogens, the development of small molecule inhibitors that target additional gut microbial metabolic functions would deliver transformative tools with the potential to greatly advance our understanding of this microbial community.
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From page 62... ...
CONCLUSIONS There are currently tremendous gaps in our knowledge of the metabolic activities associated with the human gut microbiome, preventing us from leveraging this community to enhance health and treat disease. Addressing this issue will require contributions from many scientific disciplines, but it is clear that knowledge and techniques from chemistry have the potential to facilitate leaps in our understanding of gut microbial functions.
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From page 63... ...
2014. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics.
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