Research & Publications
My lab uses microbial genetics, mass spectrometry, germfree animal models, and computational approaches to understand the mechanisms of host-microbiome interaction. We have a track record of developing new approaches for microbiology, including transposon insertion sequencing, personalized microbiota culture collections, and regulated control of microbiome gene expression in live animals. We have used these approaches to understand how commensal microbes interact with each other and their host during health and infection.
Specialized Terms: Microbiota; Microbiome; Genomics; Gnotobiotic; Germfree; Symbiosis; Gut; Flora; Bacteria; Pathogen
Extensive Research Description
My laboratory works to create new approaches for understanding the contributions of the human gut microbiome to health.
Metabolism of drugs and vitamins by the gut microbiome. Although the gut microbiome encodes a rich repository of enzymes with the potential to modify small molecules, how these activities impact clinically relevant compounds such as vitamins and medical drugs is unknown. Progress in this area could benefit the development and administration of drugs across multiple disease indications and enable co-therapies (probiotics, prebiotics, antibiotics, fecal transplant) that transiently alter an individual’s microbiome to improve their response to a drug. We combine microbial genetics, gnotobiotics, and pharmacokinetics to discover and characterize human microbiome-encoded drug- and vitamin- metabolizing enzymes in vitro and in animal models. These studies have uncovered how gut microbes recognize and transform drugs and vitamins, and define how microbiome variation can impact drug and drug metabolite levels and drug-related toxicities.
Zimmermann, M.*, Zimmermann-Kogadeeva, M.*, Wegmann, R., and Goodman, A.L. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 570(7762) p462-467 (2019). *equal contribution. PMCID: PMC6597290.
Zimmermann, M.*, Zimmermann-Kogadeeva, M.*, Wegmann, R., and Goodman, A.L. Separating host and microbiome contributions to drug metabolism and toxicity. Science 363(6427) (2019). *equal contribution. PMCID: PMC6533120.
Wexler, A.G., Schofield, W.B., Degnan, P.H., Folta-Stogniew, E., Barry, N.A., and Goodman, A.L. Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins. eLife 37138 (2018). PMCID: PMC6143338.
Degnan, P.H., Barry, N.A., Mok, K.C., Taga, M.E., and Goodman, A.L. Human gut microbes use multiple transporters to distinguish vitamin B12 analogs and compete in the gut. Cell Host & Microbe 15 p47-57 (2014). PMCID: PMC3923405.
Microbial cooperation, competition, and antagonism. My lab works to understand commensal physiology and microbiome dynamics in the gut. Together, these studies reveal critical factors that shape microbiome dynamics and highlight avenues for therapeutic manipulation of these communities.
Cullen, T.W., Schofield, W.B., Barry, N.A., Putnam, E.E., Rundell, E.A., Trent, M.S., Degnan, P.H., Booth, C.J., Yu, H., and Goodman, A.L. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation. Science 347(6218) p170-175 (2015). PMCID: PMC4388331.
Wexler, A.G., Bao, Y., Whitney, J.C., Bobay, L-M., Xavier, J.B., Schofield, W.B., Barry, N.A., Russell, A.B., Tran, B.Q., Goo, Y., Goodlett, D.R., Ochman, H.O., Mougous, J.D., and Goodman, A.L. Human symbionts inject and neutralize antibacterial toxins to persist in the gut. Proceedings of the National Academy of Sciences 113(13) p3639-44 (2016). PMCID: PMC4822603.
Russell, A.B., Wexler, A.G., Harding, B.N., Whitney, J.C., Bohn, A.J., Goo, A.Y., Tran, B.Q., Barry, N.A., Zheng, H., Peterson, S.B., Chou, S., Gonen, T., Goodlett, D.R., Goodman, A.L.*, and Mougous, J.D.* A Type VI secretion-related pathway in Bacteroidetes mediates interbacterial antagonism. Cell Host & Microbe 16 p1-10 (2014). PMCID: PMC4136423. (*co-corresponding authors).
Schofield, W.B.*, Zimmermann-Kogadeeva, M.*, Zimmermann, M., Barry, N.A., and Goodman, A.L. The stringent response determines the ability of a commensal bacterium to survive starvation and to persist in the gut. Cell Host & Microbe 24(1) p120-132 (2018). (*equal contribution) PMCID: PMC6086485.
Functional genomic tools for microbiome analysis. We have a track record of innovative approaches for microbiome and microbiology research. For example, we developed transposon insertion sequencing (INSeq), which we applied to conduct the first genomewide screen for fitness determinants of a human commensal in a mammalian host. This study established that membership in the gut microbiome is not a passive process, but instead reflects the coordinated engagement of hundreds of previously unrecognized mechanisms for fitness in this environment. We also developed approaches for creating personalized human gut microbiota culture collections that capture the majority of an individual’s gut microbiota. This strategy is now widely used to directly establish specific contributions of individual species in microbial communities. In another example, we established the first genetic system for controlling microbiome gene expression in the mouse gut through a synthetic inducer provided in drinking water. We applied this technique to measure dose-response relationships between microbiome activities and host responses.
Lim, B., Zimmermann, M., Barry, N.A., and Goodman, A.L. Engineered regulatory systems modulate gene expression of human commensals in the gut. Cell 169(3) p547-558 (2017). PMCID: PMC5532740.
Bencivenga-Barry, N.A., Lim, B., Herrara, C.M., Trent, M.S., and Goodman, A.L. Genetic manipulation of wild human gut Bacteroides. Journal of Bacteriology In press (2019).
Bacteria; Germ-Free Life; Symbiosis; Genomics; Microbial Consortia; Microbiota