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Infection trains the host for microbiota-enhanced resistance to pathogens
Open accessAbstract
The microbiota shields the host against infections in a process known as colonization resistance. How infections themselves shape this fundamental process remains largely unknown. Here, we show that gut microbiota from previously infected hosts display enhanced resistance to infection. This long-term functional remodeling is associated with altered bile acid metabolism leading to the expansion of taxa that utilize the sulfonic acid taurine. Notably, supplying exogenous taurine alone is sufficient to induce this alteration in microbiota function and enhance resistance. Mechanistically, taurine potentiates the microbiota's production of sulfide, an inhibitor of cellular respiration, which is key to host invasion by numerous pathogens. As such, pharmaceutical sequestration of sulfide perturbs the microbiota's composition and promotes pathogen invasion. Together, this work reveals a process by which the host, triggered by infection, can deploy taurine as a nutrient to nourish and train the microbiota, promoting its resistance to subsequent infection.
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“For example, deconjugation of taurine-conjugated BAs has been shown to impact the establishment of colonization resistance against Klebsiella pneumoniae, the development of colorectal cancer and more recently metabolic disease43–45.”
From Bile salt hydrolases shape the bile acid landscape and restrict Clostridioides difficile growth in the murine gut (2023) · cites this paper as [44]
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“Reanalysis of the shotgun datasets using the same bioinformatics pipeline11,34,35 mostly reproduced reported taxonomic differences between Rs and NRs with minimal overlap between datasets (Supplementary Fig. 7a–d).”
From Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1 (2022) · cites this paper as [34]
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Metadata
- Authors
- Stacy, A., Andrade-Oliveira, V., McCulloch, J. A., Hild, B., Oh, J. H., Perez-Chaparro, P. J., Sim, C. K., Lim, A. I., Link, V. M., Enamorado, M., Trinchieri, G., Segre, J. A., Rehermann, B., & Belkaid, Y.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Stacy, Apollo
- Belkaid, Yasmine
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-02
- Volume
- 184
- Issue
- 3
- Pages
- 615-627.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8786454
- OpenAlex
- W3118956265
- Cited by
- 239
- References
- 70
- Citations by year
- 2026: 27 · 2025: 37 · 2024: 38 · 2023: 56 · 2022: 46 · 2021: 35
- FWCI
- 13.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Servier
- National Institute of General Medical Sciences (1FI2GM128736-01)
- National Cancer Institute
- Human Frontier Science Program (LT000191/2018)
- Cancer Research Institute
- University of California, Los Angeles
- College of Engineering, University of Wisconsin-Madison
- Deutsche Forschungsgemeinschaft (HI 2088/1-1)
- National Institute of Allergy and Infectious Diseases (1ZIAAI001115-11)
- National Institutes of Health
- National Human Genome Research Institute (1ZIAHG000180-19)
- National Institute of Diabetes and Digestive and Kidney Diseases (1ZIADK054508-22)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- gut microbiota, colonization resistance, taurine, bile acid metabolism, sulfide, host-pathogen interaction, host defense against infection
- MeSH terms
- Gastrointestinal Microbiome, Animals, Bacterial Infections, Immunity, Mice, Inbred C57BL, Sulfides, Taurine, Colony Count, Microbial, Mice, Host-Pathogen Interactions
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