Gastrointestinal tract
Phillip Hylemon, Ph.D., Jasmohan Bajaj, M.D., and Arun Sanyal, M.D. have collaborated extensively for the past decade, with additional involvement from Huiping Zhou, Ph.D. They have co-authored many manuscripts and participated in many collaborative grants. Most recently, they received a large philanthropic award to establish an Institute for Liver Disease and Metabolic Health.
The gastrointestinal team has several additional collaborators, including Ekaterina Smirnova, Ph.D., assistant professor in the Department of Biostatistics, who has been helping to dissect their microbiome data, although this effort has yet to manifest in manuscripts or new grants. Gregory Buck, Ph.D., and Myrna Serrano, Ph.D. have also partnered with the group in the past to generate genomic sequences and transcription profiles of selected relevant gut bacteria.
Team members
- Gastrointestinal area lead
- Professor, Department of Microbiology and Immunology, School of Medicine
- Professor, Department of Microbiology and Immunology, School of Medicine
- Professor, Department of Internal Medicine, School of Medicine
- Director, Center for Integrative Life Sciences Education, VCU Life Sciences
- Combining computational and experimental approaches to understand and apply aspects of the genotype-phenotype relationship in microbes
- Harvey and Gladys Haag Professor and vice chair, Department of Pharmacology and Toxicology, School of Medicine
- Studying the impact of the gut microbiome on on antinociceptive tolerance and opioid-induced hyperalgesia; he has recently begun collaborating with Serrano
- Associate professor, Center for Biological Data Science
- Associate dean for research, scholarship and innovation, School of Nursing
- Studying the relationships of the gut microbiome, stress, sleep and addiction on the health of neonates and infants, including a collaboration with Buck and Serrano on one successful and one pending proposal
- Assistant professor, Department of Pediatrics, School of Medicine
- Professor and interim chair, Division of Gastroenterology, Hepatology and Nutrition
- Associate professor, Department of Forensic Science, College of Humanities and Sciences
Representative projects
Some representative collaborative grants and publications include the following.
Bile acid production by gut microbiota and nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Recent work has shown that increases in deoxycholic acid in feces and serum of individuals with nonalcoholic steatohepatitis with advanced fibrosis. In humans, increased deoxycholic acid is associated with a decrease in large bowel transit time, increased levels of bile acid 7α-dehydroxylating gut bacteria and increases in fecal. Deoxycholic acid can accumulate in the enterohepatic circulation of humans, but not in other animals, due to lack of bile acid 7α-hydroxylation which regenerates cholic acid. Deoxycholic acid activates hepatic cell signaling pathways linked to hepatic inflammation and fibrosis, antagonizes FXR activation and induces DNA damage.
This team is comparing the levels of cholic acid 7α-dehydroxylating bacteria in fecal samples from Control Patients with varying clinically relevant stages of fibrosis by measuring 7α-dehydroxylating bacteria in serial dilutions of feces and quantification of bile acid inducible genes by RT-PCR. Bile acid bacterial metabolites in these experiments are quantified using LC-MS-MS. Long chain fatty acids including: acetate, propionate, butyrate and pH values are measured in all fecal samples. These analyses lead to bile acid metabolites that will be useful for determining disease progression and treatment of nonalcoholic steatohepatitis.