Microbial regulation of the L cell transcriptome

TY - JOUR

T1 - Microbial regulation of the L cell transcriptome

AU - Arora, Tulika

AU - Akrami, Rozita

AU - Pais, Ramona

AU - Bergqvist, Linda

AU - Johansson, Bengt R

AU - Schwartz, Thue W.

AU - Reimann, Frank

AU - Gribble, Fiona M

AU - Bäckhed, Fredrik

PY - 2018

Y1 - 2018

N2 - 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). Lposcells 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 Lposcells from ileum. This finding was corroborated by electron microscopy of Lposcells 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 Lposcells 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.

AB - 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). Lposcells 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 Lposcells from ileum. This finding was corroborated by electron microscopy of Lposcells 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 Lposcells 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.

U2 - 10.1038/s41598-017-18079-2

DO - 10.1038/s41598-017-18079-2

M3 - Journal article

C2 - 29352262

SN - 2045-2322

VL - 8

SP - 1

EP - 9

JO - Scientific Reports

JF - Scientific Reports

M1 - 1207

ER -