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Host inflammation drives adaptive evolution in gut bacteria

Award Number: F31DK143742
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 09/30/2027

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Host inflammation drives adaptive evolution in gut bacteria - Host inflammation drives adaptive evolution in gut bacteria Summary Inflammatory bowel disease (IBD) has long been associated with compositional and metabolic changes in the gut microbiota, yet extensive research efforts have failed to identify a single pathogenic microorganism as the causative agent. Here, I hypothesize that gut inflammation facilitates adaptations in commensal bacteria that further exacerbates disease in IBD. Exposure to gut inflammation exposes bacterial strains to reactive oxygen species (ROS), creating a hostile environment that drives microbial adaptation. I will use the human commensal Bacteroides fragilis as a model system, as this gut-resident bacteria is known to promote anti-inflammatory responses during steady-state. Although traditionally considered a strict anaerobe, B. fragilis has a unique ability to tolerate and even utilize nanomolar concentrations of oxygen. In addition, it can acquire metabolic adaptations due to the strong selective pressures of oxidative stress which enable its persistence in the intestine despite the extreme inflammatory environment. Whether these subsequent changes alter its metabolic output and host interactions remains unexplored. Thus, there is a critical need to understand how the inflamed gut environment shapes commensal bacteria metabolism. We hypothesize that gut inflammation induces specific adaptive responses in B. fragilis, altering its immunomodulatory functions and metabolic output to worsen IBD symptoms. The goal of this proposal is to elucidate how gut inflammation drives adaptations in B. fragilis, and whether these adaptations contribute to disease progression in IBD. To achieve this goal, I will evolve B. fragilis strains using in vitro and in vivo models of inflammation, characterize the transcriptional and metabolic responses of B. fragilis to inflammatory conditions, and assess the functional changes in evolved B. fragilis strains and their subsequent impact on gut inflammation. The findings of this study will significantly advance our understanding of microbial dynamics in IBD, with broad implications for microbiology, immunology, and the development of therapeutic strategies targeting the gut microbiota.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $44,157 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	4/8/2026	NEW	$0
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/8/2026	NEW	$44,157
														Subtotal = $44,157

Grand Total All Awards = $44,157

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Host inflammation drives adaptive evolution in gut bacteria

Award Number: F31DK143742

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 09/30/2027

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