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Microbial regulation of the L cell transcriptome

Journal article
Authors Tulika Arora
Rozita Akrami
R. Pais
Linda Bergqvist
Bengt R Johansson
T. W. Schwartz
F. Reimann
F. M. Gribble
Fredrik Bäckhed
Published in Scientific Reports
Volume 8
Issue 1
ISSN 2045-2322
Publication year 2018
Published at Wallenberg Laboratory
Institute of Medicine, Department of Rheumatology and Inflammation Research
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Links doi.org/10.1038/s41598-017-18079-2
Keywords ENTEROENDOCRINE CELLS; GUT MICROBIOTA; PEPTIDE-1 SECRETION; R PACKAGE; COLON; EXPRESSION; PHYSIOLOGY; METABOLISM
Subject categories Cell and Molecular Biology

Abstract

L cells are an important class of enteroendocrine cells secreting hormones such as glucagon like peptide-1 and peptide YY that have several metabolic and physiological effects. The gut is home to trillions of bacteria affecting host physiology, but there has been limited understanding about how the microbiota affects gene expression in L cells. Thus, we rederived the reporter mouse strain, GLU-Venus expressing yellow fluorescent protein under the control of the proglucagon gene, as germ-free (GF). Lpos cells from ileum and colon of GF and conventionally raised (CONV-R) GLU-Venus mice were isolated and subjected to transcriptomic profiling. We observed that the microbiota exerted major effects on ileal L cells. Gene Ontology enrichment analysis revealed that microbiota suppressed biological processes related to vesicle localization and synaptic vesicle cycling in Lpos cells from ileum. This finding was corroborated by electron microscopy of Lpos cells showing reduced numbers of vesicles as well as by demonstrating decreased intracellular GLP-1 content in primary cultures from ileum of CONV-R compared with GF GLU-Venus mice. By analysing Lpos cells following colonization of GF mice we observed that the greatest transcriptional regulation was evident within 1 day of colonization. Thus, the microbiota has a rapid and pronounced effect on the L cell transcriptome, predominantly in the ileum. © 2018 The Author(s).

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