Andrew Goodman, PhD

The Goodman lab works to understand the contributions of the human gut microbiome to health, disease, and response to treatment.

The role of the gut microbiome in drug response. Although the gut microbiome encodes a rich repository of enzymes with the potential to modify small molecules, how these activities impact clinically relevant compounds including medical drugs is unknown. Progress in this area could benefit the development and administration of drugs across multiple disease indications and enable co-therapies 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 drug-microbiome interactions in vitro and in animal models. These studies have uncovered how gut microbes transform medical drugs, and define how microbiome variation can impact drug and drug metabolite levels and drug-related toxicities.

Example publications:

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.

Mechanisms of host-pathogen-microbiome interaction. These studies provide examples of our contributions to understanding the molecular mechanisms that dictate the interactions between human gut commensal bacteria, invading enteropathogens, and their host. For example, we have uncovered commensal-encoded mechanisms for resilience during infection with gastrointestinal bacterial pathogens. We established the underlying genes and biochemical activities, demonstrated their importance in a range of animal models, and completed an IRB-approved human study with complementary results. These studies suggest that commensal-encoded mechanisms for resilience during infection are a counterpart to host-encoded mechanisms for tolerance of the microbiota.

Example publications:

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.

Tawk, C., Lim, B., Bencivenga-Barry, N.A., Lees, H.J., Ramos, R.J., Cross, J., and Goodman, A.L. Infection leaves a genetic and functional mark on the gut population of a commensal bacterium. Cell Host & Microbe 31(5) p811-826 (2023). PMID: 37119822

Cooperation and competition in the gut microbiome. We also work to understand the mechanisms of interaction between commensal microbes in the human gut, including nutrient competition and the production of secreted factors that shape the microbiome.

Example publications:

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.

Bao, Y., Verdegaal, A.A., Anderson, B.W., Barry, N.A., He, J., Gao, X., and Goodman, A.L. A common pathway for activation of host-targeting and bacteria-targeting toxins in human intestinal bacteria. mBio 12(4): e0056621. PMCID: PMC8406203.

Putnam, E.E., Abellon-Ruiz, J., Killinger, B.J., Rosnow, J.J., Wexler, A.G., Folta-Stogniew, E., Wright, A.T., van den Berg, B., and Goodman, A.L. Gut commensal Bacteroidetes encode a novel class of vitamin-B₁₂ binding proteins. mBio 13(2) e0284521 (2022). PMCID: PMC8941943.

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.

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.

New approaches 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.

Example publications:

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 202(3) e00544-19 (2020). PMCID: PMC6964735.

Zimmermann-Kogadeeva, M., Zimmermann, M., and Goodman, A.L. Insights from pharmacokinetic models of host-microbiome drug metabolism. Gut Microbes (2019).

Goodman, A.L., Kallstrom, G., Faith, J.J., Reyes, A., Moore, A., Dantas, G., and Gordon, J.I. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proceedings of the National Academy of Sciences 108(15) p6252-6257 (2011). PMCID: PMC3076821.

Goodman, A.L., McNulty, N.P., Zhao, Y., Leip, D., Mitra, R.D., Lozupone, C.A., Knight, R., and Gordon, J.I. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host & Microbe 6(3) p279-289 (2009). PMCID: PMC2895552.