The G Protein-Coupled Receptor, VPAC1, Mediates Vasoactive Intestinal Peptide-Dependent Functional Homeostasis of the Gut Microbiota

Aaron C. Ericsson; Manpreet Bains; Zachary McAdams; Justin Daniels; Susheel B. Busi; James A. Waschek; Glenn P. Dorsam

Gastro Hep Advances (Jan 2022)

The G Protein-Coupled Receptor, VPAC1, Mediates Vasoactive Intestinal Peptide-Dependent Functional Homeostasis of the Gut Microbiota

Aaron C. Ericsson,
Manpreet Bains,
Zachary McAdams,
Justin Daniels,
Susheel B. Busi,
James A. Waschek,
Glenn P. Dorsam

Affiliations

Aaron C. Ericsson: Department of Veterinary Pathobiology, University of Missouri Metagenomics Center, College of Veterinary Medicine, University of Missouri, Columbia, Missouri
Manpreet Bains: Department of Microbiological Sciences, College of Agriculture, Food Systems and Natural Resources, North Dakota State University, Fargo, North Dakota
Zachary McAdams: Department of Veterinary Pathobiology, University of Missouri Metagenomics Center, College of Veterinary Medicine, University of Missouri, Columbia, Missouri
Justin Daniels: Department of Microbiological Sciences, College of Agriculture, Food Systems and Natural Resources, North Dakota State University, Fargo, North Dakota
Susheel B. Busi: Department of Systems Ecology, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
James A. Waschek: Department of Psychiatry and Biobehavioral Sciences, Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior/Neuropsychiatric Institute, University of California, Los Angeles, Los Angeles, California
Glenn P. Dorsam: Department of Microbiological Sciences, College of Agriculture, Food Systems and Natural Resources, North Dakota State University, Fargo, North Dakota; Correspondence: Address correspondence to: Glenn P. Dorsam, PhD, Department of Microbiological Sciences, 1230 Albrecht Blvd, North Dakota State University, Fargo, North Dakota 58102.

Journal volume & issue: Vol. 1, no. 2
pp. 253 – 264

Abstract

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Background and Aims: Vasoactive intestinal peptide (VIP) is a neuropeptide involved in the regulation of feeding behavior and circadian rhythms, metabolism, and immunity. Previous studies revealed the homeostatic effects of VIP signaling on the gut microbiota. VIP-deficient mice demonstrate a gut microbiota dysbiosis characterized by reduced α-diversity and decreased relative abundance (RA) of Gram-positive Firmicutes. However, the mechanism by which VIP signaling affects changes in the microbiota is unknown. Methods: To investigate the role of the 2 cognate G protein-coupled receptors for VIP (VPAC1 and VPAC2) in VIP-mediated homeostasis of the microbiota, fecal samples from VPAC1- and VPAC2-deficient, heterozygous, and wild-type littermate mice were assessed via targeted amplicon sequencing. Their microbiota profiles were additionally compared with microbiota from VIP-deficient, heterozygous, and wild-type littermates, where genotype-dependent changes in the composition and predicted function of each cohort were compared. Results: While wild-type mice in each line differed in α-diversity and β-diversity, consistent changes in both metrics were observed in VIP-deficient and VPAC1-deficient mice. This includes a dramatic reduction in α-diversity, increased RA of Proteobacteria and Bacteroidetes, and decreased RA of Lachnospiraceae, Ruminococcaceae, Muribaculaceae, and Rikenellaceae. Specific amplicon sequence variants and predicted functions found to differ significantly based on VIP or VPAC1 genotype were concordant in their directions of change. Multiplatform predicted functional profiling suggested a defective VIP-VPAC1 axis was associated with reduced amino acid degradation along with reduced quinol and quinone biosynthesis. Furthermore, alterations in predicted functions include increased sugar degradation, nitrate reduction, and fatty acid biosynthetic pathways, among other changes. Conclusion: We conclude that VIP signaling through VPAC1 is critical for the maintenance of normal function of the gut microbiota.

Published in Gastro Hep Advances

ISSN: 2772-5723 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the digestive system. Gastroenterology
Website: https://www.sciencedirect.com/journal/gastro-hep-advances

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