{"id":4058,"date":"2026-05-24T16:04:06","date_gmt":"2026-05-24T16:04:06","guid":{"rendered":"https:\/\/www.vanderbilt.edu\/evolution\/?p=4058"},"modified":"2026-05-24T16:05:03","modified_gmt":"2026-05-24T16:05:03","slug":"vanderbilt_team_discovers_how_a_gut_pathogen_thrives_in_inflammation","status":"publish","type":"post","link":"https:\/\/www.vanderbilt.edu\/evolution\/vanderbilt_team_discovers_how_a_gut_pathogen_thrives_in_inflammation\/","title":{"rendered":"Vanderbilt Team Discovers How a Gut Pathogen Thrives in Inflammation"},"content":{"rendered":"

By Andy Flick, Evolutionary Studies scientific coordinator<\/em><\/p>\n

While someone may not often think about the bacteria living in their gut, assistant professor of Pathology, Microbiology and Immunology Wenhan Zhu<\/a> and his team, Luisella Spiga, Ryan Fansler, Yifan Wu, and Abigail Rose<\/a> certainly do. They\u2019ve carved out a niche studying a common gut microbe, Bacteroides fragilis<\/em>. In many people, these bacteria live harmlessly and perhaps assist with digestion and immune education; however, the team specializes in strains that can cause infection.<\/p>\n

According to Zhu, \u201cunderstanding how these strains behave\u2014why and how they cause inflammation\u2014is critical because they sit at the intersection of the microbiome, the immune system, and chronic diseases such as colorectal cancer.\u201d<\/p>\n

\"Zhu<\/a>
The Zhu Lab<\/figcaption><\/figure>\n

Their new manuscript published in Cell <\/i>looks at a toxin produced by these bacteria in the gut. This toxin, aptly named Bacteroides fragilis<\/em> toxin, manipulates the cells lining the gut and disrupts normal biological pathways for its own advantage. The result is a gut environment that is more oxygenated than it should be \u2014 and toxin-producing strains, it turns out, are uniquely equipped to take advantage of that. The culprit turned out to be something hiding in plain sight: a core metabolic pathway called the TCA (tricarboxylic acid) cycle, which typically operates as two branches in a bacterium like this.<\/p>\n

Zhu explained, \u201cwe noticed that toxin-producing strains behaved very differently from typical anaerobes, bacteria that cannot grow in the presence of oxygen, in the inflamed gut, which is more oxygenated than a healthy intestine. That observation pushed us to look beyond individual genes and instead ask whether their core metabolism evolved differently. We noted that these bacteria code for and operate a complete TCA cycle, often associated with oxygen use, rather than relying solely on the branched pathways typical of classical anaerobes. This complete TCA cycle, similar in principle to the one used in human cells, emerged as a key pathway that explained this unexpected oxygen tolerance.\u201d<\/p>\n

He explained that chronic inflammation and altered metabolism are key risk factors for colon cancer, and ETBF’s ability to thrive in inflamed gut helps explain its strong association with tumor development. Understanding how these bacteria exploit the inflamed gut may ultimately point toward new strategies for interrupting that cycle.<\/p>\n

Spiga, Fansler, Wu, and Rose continued, \u201cthis bacterium doesn\u2019t just tolerate inflammation; it can shape the gut environment to support a more oxidative growth strategy at the tissue surface. Seeing signals consistent with ETBF (enterotoxigenic Bacteroides fragilis<\/em>) thriving in that inflamed, more oxygenated niche really shifted how we think about \u2018anaerobes\u2019 in disease settings.\u201d<\/p>\n

To place these findings in a broader evolutionary context, the team collaborated with the lab of assistant professor of biological sciences Megan Behringer. Owen Hale, a graduate student in the Behringer lab explained that they used comparative genomics analysis to reveal that ETBF’s unusual metabolic features are not a quirk of a single strain but part of a larger pattern tied to survival in oxygenated niches.<\/p>\n

Rose explained that oxygen tolerance is one of the core features of a dependable probiotic. Many beneficial gut bacteria are extremely oxygen-sensitive, creating challenges for manufacturing, storage, and delivery. The problem is compounded biologically: inflammation, induced by ETBF or other triggers, can oxygenate the gut, suppressing the very anaerobic microbes we want to preserve or restore. She is now leading the efforts to engineer strict anaerobic commensals that can better withstand oxygen, potentially helping beneficial microbes survive and function where they are needed most.<\/p>\n

Citation: Spiga, L., Fansler, R.T., Wu, Y., Grote, A., Langford-Butler, M., Miller, A.K., Neal, M., Hale, O.F., Singla, D., Calcutt, M.W. Rose, A.E., Bresson, M.M., Schrimpe-Rutledge, A.C., Berdy, B., Codreanu S.G., Washington, M.K., Bratton, B.P., Sherrod, S.D., McLean, J.A., Zengler, K., Sears, C.L., Behringer, M.G., Gnirke, A., Tao, L., Linvy, J., Olivares-Villagomez, D., Earl, A.M., Zhu, W. 2026. An anaerobic pathogen rewires host metabolism to fuel oxidative growth in the inflamed gut.<\/a> Cell<\/i>.<\/p>\n

Funding Statement: This work was supported by the CoEvoD fellowship (VU Evolutionary Studies CoEvoD Fellowship 001<\/span>) National Institute of Allergy and Infectious Diseases (F31AI178950), National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK134692), National Institute of General Medical Sciences (1R35GM147470, R35GM150625), V Foundation for Cancer Research (V2022-032), Colorectal Cancer Alliance (10065978), G. Harold & Leila Y. Mathers Foundation (MF-2207-03128), Metabolomics Workbench\/National Metabolomics Data Repository (U2C-DK119886), Common Fund Data Ecosystem (3OT2OD030544), Metabolomics Consortium Coordinating Center (1U2C-DK119889)<\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

By Andy Flick, Evolutionary Studies scientific coordinator While someone may not often think about the bacteria living in their gut, assistant professor of Pathology, Microbiology and Immunology Wenhan Zhu and his team, Luisella Spiga, Ryan Fansler, Yifan Wu, and Abigail Rose certainly do. They\u2019ve carved out a niche studying a common gut microbe, Bacteroides fragilis….<\/p>\n","protected":false},"author":2421,"featured_media":4059,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"spay_email":"","jetpack_publicize_message":"","jetpack_is_tweetstorm":false,"jetpack_publicize_feature_enabled":true},"categories":[7],"tags":[209,193,15,3,210,208],"acf":[],"yoast_head":"\n\n\n\n\n\n\n\n\n\n\n\n\t\n\t\n\t\n\n\n\t\n\t\n\t\n