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Research

Understanding the association between gut microbiome dysbiosis and gastrointestinal diseases

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An imbalanced gut microbiota can cause  several diseases such as Clostridioides difficile infection (CDI), colorectal cancer (CRC), inflammatory bowel disease (IBD), and obesity.  Our lab is broadly interested in understanding the bacterial ecological changes that are associated with diseases such as CDI. In the longer term, a better understanding of the gut ecology that cause such diseases could be used to develop preventive or therapeutic measures against CDI and other gut problems. Within the broad theme of gut dybiosis associated diseases, we work in the following three areas.

Research area 1: Which species in the gut microbiome is important to prevent enteric infection?

The invasion of the gut by pathogens such as C. difficile often is the result of the depletion of more than one species from the healthy gut. Healthy state can be restored by fecal transplantation. Our goal in this project is to determine the minimum number of species needed as an alternative to fecal transplantation to prevent CDI and other enteric infections.  We do this using a bottom up approach. We culture healthy microbiota as a library and then test several simple to complex synthetic communities in vitro and in vivo model systems to determine the most effect species type and composition that prevent pathogen colonization.

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Please see our paper in mSystems for the preliminary results

Research area 2: How does microbiota change flavonoid metabolism and gut health?

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Dietary flavonoids such as quercetin can be metabolized by some gut bacteria. Some of these bacteria produce negative effect while some could be beneficial in controlling diseases such as IBD and CRC.

 

We are screening our gut microbiota library to identify species and the enzymes that mediate flavonoid biotransformation.

 

In the long term, our goal is to develop bio-engineered probiotics over expressing flavonoid metabolizing enzymes that improve gut health.  

 

Please see  our papers in Front Microbiol and IJMS for the preliminary results.

Research area 3: Better understand how pathogen evolution allow increased gut invasion and transmission

Pathogens evolve  by genome rearrangements that may lead to increased virulence and antibiotic resistance which may make them more pathogenic. To better understand the genomic basis of pathogenicity, we use whole genome sequencing and comparative genomic analysis of pathogens such as Salmonella and C. difficile. We integrate computational and experimental methods to better understand the evolution of these pathogens.

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The figure above is a comparison of Salmonella Dublin genomes from all over the world. We show that

S. Dublin strains from the United States has significantly larger genome size that may play a role in its

transmission. Please see our paper in Genome Biology and Evolution for details.