Grants and Contracts per year
Grants and Contracts Details
Description
The mammalian gastrointestinal tract (GI) harbors a highly complex and abundant ensemble of bacteria
that flourish in a nutrient-rich environment while profoundly influencing many aspects of host biology. The
alteration in gut microbiota, which is termed microbial dysbiosis, is associated with many diseases,
including inflammatory bowel disease (IBD), neurological disorders, obesity, diabetes, cardiovascular, and
other metabolic syndromes. Besides, the dysbiotic gut microbiota has been reported to influence the
pathogenesis of many human pathogens, including Salmonella, Escherichia, Yersinia, and Vibrio, which
cause GI infections and inflammation. The mammalian intestine harbors a diverse array of microbial
metabolites, which are small molecules produced by cells. To determine the mechanistic functions of
microbiota-associated (microbial) metabolites, we performed (1) ultra-performance liquid
chromatograph-mass spectrometry (QEHF)-based global metabolomic profiling, (2) metagenomic analysis
and 16s profiling, and (3) metatranscriptomic analysis. Our preliminary meta’omic analysis identified
microbiota, microbial genes, and metabolites differentially abundant during chronic inflammation. We
found that the specific microbiome-associated metabolites are abundantly present during inflammation.
Furthermore, our data show that microbiota-associated metabolite stimulates expression and activation of
proinflammatory G-protein coupled receptor GPR4 in gut enterocytes. Our central hypothesis is that gut
microbial-specific metabolite is the key regulator of the dysbiotic bacterial survival, fitness, and virulence
during intestinal dysbiosis and requires GPR4 for the expansion in the intestine during inflammation and
infections. The information generated from this CPRI award will provide high-impact preliminary data to
prepare R01 applications by harnessing the knowledge of gut microbial metabolites and molecules, which
could provide novel therapeutic potentials by targeting microbial metabolism to restore a healthy
microbiome, eliminate pathogens and ameliorate diseases.
Status | Finished |
---|---|
Effective start/end date | 3/1/20 → 1/31/22 |
Funding
- National Institute of General Medical Sciences
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Projects
- 1 Finished
-
COBRE in Pharmaceutical Research and Innovation
Thorson, J., Adams, V., Alam, M., Burgess, D., Dwoskin, L., Feola, D., Garneau-Tsodikova, S., Gensel, J., Grady, M., Korotkov, K., Mahmoud, K. A., Pack, D., Park, J., Prisinzano, T., Shaffer, C., Stevenson, B., Tiruvannamalai Annam, R., Van Lanen, S., Venditto, V., Zhan, C., Awuah, S., Daugherty, A., Glazer, E., Graf, G., Kolesar, J., Korotkova, N., Leggas, M., Richards, C., Rohr, J., Sen, P., Sturgill, J., Sviripa, V., Watt, D. & Webb, N.
National Institute of General Medical Sciences
3/1/20 → 1/31/22
Project: Research project