Antibodies Set Boundaries Limiting Microbial Metabolite Penetration and the Resultant Mammalian Host Response.

Uchimura, Yasuhiro; Fuhrer, Tobias; Li, Hai; Lawson, Melissa A.; Zimmermann, Michael; Yilmaz, Bahtiyar; Zindel, Joel; Ronchi, Francesca; Sorribas Olivera, Marcel; Hapfelmeier, Siegfried; Ganal-Vonarburg, Stephanie C.; Gomez de Agüero, Mercedes; McCoy, Kathleen D.; Sauer, Uwe; Macpherson, Andrew J. (2018). Antibodies Set Boundaries Limiting Microbial Metabolite Penetration and the Resultant Mammalian Host Response. Immunity, 49(3), 545-559.e5. Cell Press 10.1016/j.immuni.2018.08.004

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Although the mammalian microbiota is well contained within the intestine, it profoundly shapes development and metabolism of almost every host organ. We questioned the range and depth of microbial metabolite penetration into the host, and how this is modulated by intestinal immunity. Chemically identical microbial and host metabolites were distinguished by stable isotope tracing from C-labeled live non-replicating Escherichia coli, differentiating C host isotopes with high-resolution mass spectrometry. Hundreds of endogenous microbial compounds penetrated 23 host tissues and fluids after intestinal exposure: subsequent C host metabolome signatures included lipidemia, reduced glycolysis, and inflammation. Penetrant bacterial metabolites from the small intestine were rapidly cleared into the urine, whereas induced antibodies curtailed microbial metabolite exposure by accelerating intestinal bacterial transit into the colon where metabolite transport mechanisms are limiting. Pervasive penetration of microbial molecules can cause extensive host tissue responses: these are limited by immune and non-immune intestinal mucosal adaptations to the microbiota.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Gastroenterology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Gastroenterologie / Mukosale Immunologie

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Viszeralchirurgie

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Visceral Surgery

UniBE Contributor:

Uchimura, Yasuhiro; Li, Hai; Lawson, Melissa; Yilmaz, Bahtiyar; Zindel, Joel; Ronchi, Francesca; Sorribas Olivera, Marcel; Hapfelmeier, Siegfried Hektor; Ganal-Vonarburg, Stephanie; Gomez de Agüero Tamargo, Maria de la Mercedes; McCoy, Kathleen and Macpherson, Andrew

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1074-7613

Publisher:

Cell Press

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

09 Jan 2019 09:46

Last Modified:

09 Jan 2019 09:46

Publisher DOI:

10.1016/j.immuni.2018.08.004

PubMed ID:

30193848

Uncontrolled Keywords:

(13)C-isotope tracing IgA colonization germ free inflammation intestinal transit lipidemia metabolomics microbial metabolites microbiota

BORIS DOI:

10.7892/boris.122376

URI:

https://boris.unibe.ch/id/eprint/122376

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