Andrew Goodman, PhD
Research & Publications
Biography
News
Research Summary
My lab uses microbial genetics, mass spectrometry, germfree animal models, and computational approaches to understand the mechanisms of host-microbiome interaction and gut microbial ecology. We work to develop 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 impact the efficacy and toxicity of medical drugs and other small molecules.
Specialized Terms: Microbiota; Microbiome; Gnotobiotic; Germfree; Symbiosis; Gut; Flora; Bacteria; Pathogen
Extensive Research Description
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.
Coauthors
Research Interests
Bacteria; Bacteroides; Symbiosis; Microbiota; Gastrointestinal Microbiome
Research Image
Selected Publications
- Metformin inhibits digestive proteases and impairs protein digestion in miceKelly C, Verdegaal A, Anderson B, Shaw W, Bencivenga-Barry N, Folta-Stogniew E, Goodman A. Metformin inhibits digestive proteases and impairs protein digestion in mice. Journal Of Biological Chemistry 2023, 299: 105363. PMID: 37863262, PMCID: PMC10663847, DOI: 10.1016/j.jbc.2023.105363.
- Infection leaves a genetic and functional mark on the gut population of a commensal bacteriumTawk C, Lim B, Bencivenga-Barry N, Lees H, Ramos R, Cross J, Goodman A. Infection leaves a genetic and functional mark on the gut population of a commensal bacterium. Cell Host & Microbe 2023 PMID: 37119822, DOI: 10.1016/j.chom.2023.04.005.
- Cross-feeding in the gut microbiome: Ecology and mechanismsCulp E, Goodman A. Cross-feeding in the gut microbiome: Ecology and mechanisms. Cell Host & Microbe 2023, 31: 485-499. PMID: 37054671, PMCID: PMC10125260, DOI: 10.1016/j.chom.2023.03.016.
- Bacteria require phase separation for fitness in the mammalian gutKrypotou E, Townsend G, Gao X, Tachiyama S, Liu J, Pokorzynski N, Goodman A, Groisman E. Bacteria require phase separation for fitness in the mammalian gut. Science 2023, 379: 1149-1156. PMID: 36927025, PMCID: PMC10148683, DOI: 10.1126/science.abn7229.
- Gut colonization by Bacteroides requires translation by an EF‐G paralog lacking GTPase activityHan W, Peng B, Wang C, Townsend G, Barry N, Peske F, Goodman A, Liu J, Rodnina M, Groisman E. Gut colonization by Bacteroides requires translation by an EF‐G paralog lacking GTPase activity. The EMBO Journal 2022, 42: e112372. PMID: 36472247, PMCID: PMC9841332, DOI: 10.15252/embj.2022112372.
- Mapping human microbiome drug metabolism by gut bacteria and their genesZimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 2019, 570: 462-467. PMID: 31158845, PMCID: PMC6597290, DOI: 10.1038/s41586-019-1291-3.
- Separating host and microbiome contributions to drug pharmacokinetics and toxicityZimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science 2019, 363 PMID: 30733391, PMCID: PMC6533120, DOI: 10.1126/science.aat9931.
- When gut bacteria spoil drug treatmentZimmermann M, Zimmermann-Kogadeeva M, Goodman A. When gut bacteria spoil drug treatment. TheScienceBreaker 2019, 05 DOI: 10.25250/thescbr.brk262.
- Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteinsWexler AG, Schofield WB, Degnan PH, Folta-Stogniew E, Barry NA, Goodman AL. Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins. ELife 2018, 7: e37138. PMID: 30226189, PMCID: PMC6143338, DOI: 10.7554/elife.37138.
- The Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the GutSchofield WB, Zimmermann-Kogadeeva M, Zimmermann M, Barry NA, Goodman AL. The Stringent Response Determines the Ability of a Commensal Bacterium to Survive Starvation and to Persist in the Gut. Cell Host & Microbe 2018, 24: 120-132.e6. PMID: 30008292, PMCID: PMC6086485, DOI: 10.1016/j.chom.2018.06.002.
- Spontaneous translocation of a human enterococcal gut pathobiont drives systemic autoimmunityVieira S, Hiltensperger M, Kumar V, Zegarra-Ruiz D, Dehner C, Barbieri A, Jain D, Goodman A, Kriegel M. Spontaneous translocation of a human enterococcal gut pathobiont drives systemic autoimmunity. The Journal Of Immunology 2018, 200: 162.10-162.10. DOI: 10.4049/jimmunol.200.supp.162.10.
- Autoantibody cross-reactivity with a microbial protein from a prevalent human gut commensal in antiphospholipid syndromeruff W, Roth A, Dehner C, Vieira S, Goodman A, Kriegel M. Autoantibody cross-reactivity with a microbial protein from a prevalent human gut commensal in antiphospholipid syndrome. The Journal Of Immunology 2017, 198: 58.4-58.4. DOI: 10.4049/jimmunol.198.supp.58.4.
- An insider's perspective: Bacteroides as a window into the microbiomeWexler AG, Goodman AL. An insider's perspective: Bacteroides as a window into the microbiome. Nature Microbiology 2017, 2: 17026. PMID: 28440278, PMCID: PMC5679392, DOI: 10.1038/nmicrobiol.2017.26.
- Engineered Regulatory Systems Modulate Gene Expression of Human Commensals in the GutLim B, Zimmermann M, Barry NA, Goodman AL. Engineered Regulatory Systems Modulate Gene Expression of Human Commensals in the Gut. Cell 2017, 169: 547-558.e15. PMID: 28431252, PMCID: PMC5532740, DOI: 10.1016/j.cell.2017.03.045.
- 64 Dysbiosis and gut barrier dysfunction in antiphospholipid syndrome as revealed by iga-seq profilingKim W, Ruff W, Aguiar C, Yu A, Vieira S, Sterpka J, Goodman A, Erkan D, Kriegel M. 64 Dysbiosis and gut barrier dysfunction in antiphospholipid syndrome as revealed by iga-seq profiling. Lupus Science & Medicine 2017, 4: a28. DOI: 10.1136/lupus-2017-000215.64.
- 234 Anti-Ro60 T and B cells in human lupus cross-react with Ro60 orthologs from cutaneous commensalsGreiling T, Dehner C, Renfroe S, Chen X, Vieira S, Ruff W, Girardi M, Goodman A, Wolin S, Kriegel M. 234 Anti-Ro60 T and B cells in human lupus cross-react with Ro60 orthologs from cutaneous commensals. Journal Of Investigative Dermatology 2016, 136: s42. DOI: 10.1016/j.jid.2016.02.263.
- Lupus T and B cell cross-reactivity between the human Ro60 autoantigen and Ro60 orthologs from the human microbiotaGreiling T, Dehner C, Renfroe S, Chen X, Vieira S, Ruff W, Goodman A, Wolin S, Kriegel M. Lupus T and B cell cross-reactivity between the human Ro60 autoantigen and Ro60 orthologs from the human microbiota. The Journal Of Immunology 2016, 196: 124.16-124.16. DOI: 10.4049/jimmunol.196.supp.124.16.
- Human symbionts inject and neutralize antibacterial toxins to persist in the gutWexler AG, Bao Y, Whitney JC, Bobay LM, Xavier JB, Schofield WB, Barry NA, Russell AB, Tran BQ, Goo YA, Goodlett DR, Ochman H, Mougous JD, Goodman AL. Human symbionts inject and neutralize antibacterial toxins to persist in the gut. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 3639-3644. PMID: 26957597, PMCID: PMC4822603, DOI: 10.1073/pnas.1525637113.
- A common gut commensal as a cross-reactive candidate in antiphospholipid syndrome (HUM3P.250)Dehner C, Ruff W, VIEIRA S, Goodman A, Kriegel M. A common gut commensal as a cross-reactive candidate in antiphospholipid syndrome (HUM3P.250). The Journal Of Immunology 2015, 194: 121.10-121.10. DOI: 10.4049/jimmunol.194.supp.121.10.
- Gut commensal dependence of autoreactivity and Th17 cells in systemic autoimmunity (MUC9P.740)Manfredo Vieira S, Ruff W, Hiltensperger M, Yu A, Goodman A, Kriegel M. Gut commensal dependence of autoreactivity and Th17 cells in systemic autoimmunity (MUC9P.740). The Journal Of Immunology 2015, 194: 205.4-205.4. DOI: 10.4049/jimmunol.194.supp.205.4.
- Cross‐reactivity of Gut Commensals and Autoantigen in Antiphospholipid SyndromeDehner C, Ruff W, Vieira S, Goodman A, Kriegel M. Cross‐reactivity of Gut Commensals and Autoantigen in Antiphospholipid Syndrome. The FASEB Journal 2015, 29 DOI: 10.1096/fasebj.29.1_supplement.142.4.
- Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammationCullen TW, Schofield WB, Barry NA, Putnam EE, Rundell EA, Trent MS, Degnan PH, Booth CJ, Yu H, Goodman AL. Antimicrobial peptide resistance mediates resilience of prominent gut commensals during inflammation. Science 2015, 347: 170-175. PMID: 25574022, PMCID: PMC4388331, DOI: 10.1126/science.1260580.
- Experimental Approaches for Defining Functional Roles of Microbes in the Human GutDantas G, Sommer MO, Degnan PH, Goodman AL. Experimental Approaches for Defining Functional Roles of Microbes in the Human Gut. Annual Review Of Microbiology 2013, 67: 459-475. PMID: 24024637, PMCID: PMC4718711, DOI: 10.1146/annurev-micro-092412-155642.
- Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic miceGoodman AL, Kallstrom G, Faith JJ, Reyes A, Moore A, Dantas G, Gordon JI. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 6252-6257. PMID: 21436049, PMCID: PMC3076821, DOI: 10.1073/pnas.1102938108.
- Identifying Genetic Determinants Needed to Establish a Human Gut Symbiont in Its HabitatGoodman AL, McNulty NP, Zhao Y, Leip D, Mitra RD, Lozupone CA, Knight R, Gordon JI. Identifying Genetic Determinants Needed to Establish a Human Gut Symbiont in Its Habitat. Cell Host & Microbe 2009, 6: 279-289. PMID: 19748469, PMCID: PMC2895552, DOI: 10.1016/j.chom.2009.08.003.
- Modulation of Bacterial Lifestyles via Two-Component Regulatory NetworksVentre I, Goodman A, Filloux A, Lory S. Modulation of Bacterial Lifestyles via Two-Component Regulatory Networks. 2007, 311-340. DOI: 10.1007/978-1-4020-6097-7_11.