Artist: Rebecca Mcgillivary, @rebmcg

The Bess Lab

Discovering & Engineering Microbiome Chemistry 

GUT REACTIONS

Within the human gastrointestinal (GI) tract there reside trillions of bacterial cells (microbiota) that harbor thousands of distinct genes (microbiome). This biosphere has evolved in the context of a diverse array of diet- and host-derived small molecules to which it is chronically exposed. Consequently, gut bacteria have developed numerous enzymes to respond to this chemical deluge; however, little is known about the chemical motifs metabolized and the impacts of those metabolites on health. The Bess Lab discovers chemical reactions encoded in the microbiome and currently uses this repertoire to impact pharmacology through prediction of microbial metabolism of small molecules; health outcomes and communication along the gut–brain and gut–endocrine axes; and gut microbiome biodiversity through metabolism of dietary fiber. We identify knowledge gaps through a biologist’s lens and build strategies to address them as chemists devoted to elucidating the fundamental mechanisms of processes. As such, we are an multi-disciplinary team  of researchers with expertise in microbiology, molecular biology, synthetic and physical organic chemistry, and gnotobiotic animal models (mice and C. elegans).

RESEARCH AREAS
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Using the Gut Microbiome to Block Parkinson's Disease Onset

Motor dysfunction, a hallmark symptom of Parkinson’s disease, occurs when a protein called α-synuclein (α-syn) forms aggregates that accumulate in and ultimately kill neurons in the motor cortex of the brain; however, these pathogenic aggregates may not originate in the brain but in the gut microbiome. We are unravelling the molecular-level mechanisms that causally link the gut microbiome to Parkinson’s disease pathogenesis.

Shaping Biodiversity in the Gut Microbiome Using Dietary Fiber

“Eat your veggies!” Although a common catchphrase, do we really know why vegetables are important for good health? The human gut microbiome seems to be a key to unlocking the health benefits of diets rich in vegetables and whole grains, but many questions remain about just how foods and gut bacteria interact. The Bess Lab is discovering which gut bacteria breakdown the dietary fiber lignocellulose, releasing molecules that promote good health. These beneficial bacteria may be the next probiotic to help people extract the maximum health benefits from a fiber-rich diet.

Predicting gut microbiota-mediated drug metabolism to impact ADME models

A concerted effort to characterize the chemical repertoire of the microbiome is needed to understand and exploit the relationship and impact of the microbiota on pharmacology and health. We use an hypothesis-guided approach to probe the chemical-reaction space of the gut microbiome. Aiming to close the gap between drug candidates and those that enter the market, characterization of microbe-mediated metabolism will enable more accurate modeling of drug disposition, impacting current approaches to drug design.

Defining the gut microbiota's role in modulating endogenous levels of hormones

Estrogens are causally linked to breast cancer incidence; however, factors impacting the inter-individual variability of circulating estrogen levels and their metabolites are poorly understood. The compositionally and functionally unique suites of bacteria residing in peoples’ GI tracts may be a crucial link between estrogen and estrogen-dependent diseases. We are elucidating the molecular mechanisms by which the gut microbiota modulates estrogen levels to provide a handle by which to alter the incidence of estrogen-dependent disease—most notably, breast cancer.