Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88
- Erik Larsson1,2,
- Valentina Tremaroli1,2,
- Ying Shiuan Lee1,2,
- Omry Koren3,
- Intawat Nookaew4,
- Ashwana Fricker3,
- Jens Nielsen4,
- Ruth E Ley3,
- Fredrik Bäckhed1,2
- 1Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden
- 2Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden
- 3Department of Microbiology, Cornell University, Ithaca, New York, USA
- 4Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden
- Correspondence to Dr Fredrik Bäckhed, Wallenberg Laboratory, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden;
Contributors EL performed research, analysed data, wrote the manuscript; VT performed research, analysed data, commented on the manuscript; YL performed research, analysed data, commented on the manuscript; OK analysed data, commented on the manuscript; IN analysed data, commented on the manuscript; AF performed research; JN analysed data, commented on the manuscript; REL analysed data, assisting in writing the manuscript; FB conceived the study, analysed data, wrote the manuscript.
- Revised 21 October 2011
- Accepted 23 October 2011
- Published Online First 23 November 2011
Background The gut microbiota has profound effects on host physiology but local host–microbial interactions in the gut are only poorly characterised and are likely to vary from the sparsely colonised duodenum to the densely colonised colon. Microorganisms are recognised by pattern recognition receptors such as Toll-like receptors, which signal through the adaptor molecule MyD88.
Methods To identify host responses induced by gut microbiota along the length of the gut and whether these required MyD88, transcriptional profiles of duodenum, jejunum, ileum and colon were compared from germ-free and conventionally raised wild-type and Myd88−/− mice. The gut microbial ecology was assessed by 454-based pyrosequencing and viruses were analysed by PCR.
Results The gut microbiota modulated the expression of a large set of genes in the small intestine and fewer genes in the colon but surprisingly few microbiota-regulated genes required MyD88 signalling. However, MyD88 was essential for microbiota-induced colonic expression of the antimicrobial genes Reg3β and Reg3γ in the epithelium, and Myd88 deficiency was associated with both a shift in bacterial diversity and a greater proportion of segmented filamentous bacteria in the small intestine. In addition, conventionally raised Myd88−/− mice had increased expression of antiviral genes in the colon, which correlated with norovirus infection in the colonic epithelium.
Conclusion This study provides a detailed description of tissue-specific host transcriptional responses to the normal gut microbiota along the length of the gut and demonstrates that the absence of MyD88 alters gut microbial ecology.
- Bacterial overgrowth
- cardiovascular disease
- gut microbiota
- Helicobacter pylori
- host response
- intestinal epithelium
- intestinal tract
- lipid metabolism
- mucosal immunity
- Toll-like receptors
Funding This work was supported by the Swedish Research Council (K2007-65X-20421-01-04), Swedish Foundation for Strategic Research, EU-funded ETHERPATHS projects (FP7-KBBE-222639, http://www.etherpaths.org) and TORNADO (FP7-KBBE-222720, http://www.fp7tornado.eu/), Åke Wiberg, Torsten and Ragnar Söderberg, Chalmers, Knut and Alice Wallenberg, and Novo Nordisk Foundations, and a LUA-ALF grant from Västra Götalandsregionen, as well as a Beckman young investigator award to REL.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement CEL files and normalised array data are available at NCBI GEO repository, accession number GSE17438. The expression data are also freely available through http://microbiota.wall.gu.se/. The 454 data set will be available at MGRAST—accession number MGP151.
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