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Gone with the Antibody

Authors :
Silvia Guglietta
Maria Rescigno
Source :
Immunity
Publication Year :
2018
Publisher :
Elsevier BV, 2018.

Abstract

Summary 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 13C-labeled live non-replicating Escherichia coli, differentiating 12C host isotopes with high-resolution mass spectrometry. Hundreds of endogenous microbial compounds penetrated 23 host tissues and fluids after intestinal exposure: subsequent 12C 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.<br />Graphical Abstract<br />Highlights • Metabolites from mutualistic bacteria broadly penetrate host tissues and organs • Bacterial metabolites induce widespread host metabolic and immunological responses • The small intestine is highly susceptible to host-microbial metabolomic exchange • Secretory immunoglobulins accelerate microbial clearance from the small intestine<br />Bacteria-derived metabolites pervade the mammalian host, shaping immunity and metabolism. Using stable isotope tracing, Uchimura and colleagues profile the scope and depth of host tissue penetration by bacterial metabolites. Extensive host immune and metabolic responses to microbial metabolite penetration are constrained by secretory antibodies that limit microbial small-intestinal dwell time.

Details

ISSN :
10747613
Volume :
49
Database :
OpenAIRE
Journal :
Immunity
Accession number :
edsair.doi.dedup.....454b26116dd035238a0e45b0dc24f227
Full Text :
https://doi.org/10.1016/j.immuni.2018.09.003