Our research focuses on microbial bile acid modification systems and the resulting impact on host signaling to influence host health and disease status.

Bile acids are gastrointestinal (GI) emulsifying molecules that present lipids for digestion and in doing so liberate vitamins D,E,K, and A. These molecules maintain microbial populations in check due to their chemical nature, their signatures and their spatial distribution in the GI tract. In turn, the complexity and diversity of gastrointestinal bile acids are dictated by microbial enzyme modification and bile acids are now recognised as important signaling molecules in the host. The microbe generated bile acid complexity can influence host processes (either locally or systemically) by interaction with cellular receptors -including FXR, TGR5, VDR, LXR, PPAR and SIP2- to impact on host metabolic processes such as circadian rhythm, lipid metabolism, energy metabolism, immune and intestinal homeostasis. Therefore, bile acid complexity and alterations to complexity can have an impact upon host health. In agreement, alterations to the gut microbiota that influence bile acid metabolism are correlated with a number of disease states and these include obesity, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colorectal cancer (CRC) and non-alcoholic liver disease (NAFLD). We are interested in characterizing bile salt and bile acid altering enzymes, their impact/s on the gut microbiota, their effects on host signaling and how these may be utilized to intervene in the disease state.

The methodologies that we employ include: microbial population analysis, strain isolation, molecular microbiology, gene expression analysis (RNA and protein), metabolite analysis (targeted and untargeted), cell line culture, biochemical assays.

Current Lab members

PhD Students

Sarah Louise Long, BSc, MSc Biotech

Jonathan Keane, BSc, MSc

Keith O’ Donoghue, BSc

Elaine Enright, B. Pharm

Research Assistant

Mr Alvaro Lopez Gallardo

Post Doctoral Researchers

Dr Kalaimathi Govindarajan

Dr Nataliya Blatt

MSc Students

Maurice Stanley

Pereira-Fantini, P.M., Bines, J.E., Lapthorne, S., Fouhy, F., Scurr, M., Cotter, P.D., Gahan, C.G. and Joyce, S.A. 2016. Short bowel syndrome (SBS)-associated alterations within the gut-liver axis evolve early and persist long-term in the piglet model of short bowel syndrome. J Gastroenterol Hepatol. doi: 10.1111/jgh.13383.

Pereira-Fantini, P.M., Lapthorne, S., Joyce, S.A., Dellios, N.L., Wilson, G., Fouhy, F., Thomas, S.L., Scurr, M., Hill, C., Gahan, C.G., Cotter, P.D., Fuller, P.J., Hardikar, W. and Bines, J.E. 2014. Altered FXR signalling is associated with bile acid dysmetabolism in short bowel syndrome-associated liver disease. J Hepatol 61, 1115-1125. doi: 10.1016/j.jhep.2014.06.025.

Joyce, S.A., MacSharry, J., Casey, P.G., Kinsella, M., Murphy, E.F., Shanahan, F., Hill, C. and Gahan, C.G. 2014. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Proceedings of the National Academy of Sciences of the United States of America 111, 7421-7426. doi: 10.1073/pnas.1323599111.

Joyce, S.A., Brachmann, A.O., Glazer, I., Lango, L., Schwar, G., Clarke, D.J. and Bode, H.B. 2008. Bacterial biosynthesis of a multipotent stilbene. Angew Chem Int Ed Engl 47, 1942-1945. doi: 10.1002/anie.200705148.

Joyce, S.A. and Clarke, D.J. 2003. A hexA homologue from Photorhabdus regulates pathogenicity, symbiosis and phenotypic variation. Mol Microbiol 47, 1445-1457.