期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-017-18079-2
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资金
- Swedish Research Council
- NovoNordisk Foundation
- Torsten Soderberg's Foundation
- Swedish Diabetes Foundation
- Swedish Heart Lung Foundation
- Goran Gustafsson's Foundation
- IngaBritt och Arne Lundbergs Foundation
- Knut and Alice Wallenberg Foundation
- ERC Consolidator Grant (European Research Council) [615362 - METABASE]
- Medical Research Council [MRC_MC_UU_12012/3, MRC_MC_UU_12012/5]
- Wellcome Trust [106262/Z/14/Z, 106263/Z/14/Z]
- Region Vastra Gotaland
- Sahlgrenska University Hospital
- MRC [MC_UU_00014/5, MC_UU_00014/3, MC_UU_12012/3, MC_UU_12012/5] Funding Source: UKRI
- Medical Research Council [MC_UU_12012/3, MC_UU_12012/5, MC_UU_12012/5/B] Funding Source: researchfish
- NNF Center for Basic Metabolic Research [Bäckhed Group, Schwartz Group] Funding Source: researchfish
- Novo Nordisk Fonden [NNF15OC0016798] Funding Source: researchfish
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). L-pos 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 L-pos cells from ileum. This finding was corroborated by electron microscopy of L-pos 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 L-pos 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.
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