Abstract
Vasoactive intestinal peptide (VIP) is crucial for gastrointestinal tract (GIT) health. VIP sustains GIT homeostasis through maintenance of the intestinal epithelial barrier and acts as a potent anti-inflammatory mediator that contributes to gut bacterial tolerance. Based on these biological functions by VIP, we hypothesized that its deficiency would alter gut microbial ecology. To this end, fecal samples from male and female VIP+/+, VIP+/–, and VIP–/– littermates (n = 47) were collected and 16S rRNA sequencing was conducted. Our data revealed significant changes in bacterial composition, biodiversity, and weight loss from VIP–/– mice compared to VIP+/+ and VIP+/– littermates, irrespective of sex. The gut bacteria compositional changes observed in VIP–/– mice was consistent with gut microbial structure changes reported for certain inflammatory and autoimmune disorders. Moreover, predicted functional changes by PICRUSt software suggested an energy surplus within the altered microbiota from VIP–/– mice. These data support that VIP plays an important role in maintaining microbiota balance, biodiversity, and GIT function, and its genetic removal results in significant gut microbiota restructuring and weight loss.
Highlights
Vasoactive intestinal peptide (VIP) is a 28 amino acid (AA) molecule
VIP is delivered to immune organs by the peripheral nervous system, including the mucosa-associated lymphoid tissues of the gastrointestinal tract (GIT), where it plays a vital role in maintaining homeostasis (Lelievre et al, 2007)
We report that genetic deletion of the VIP locus (VIP−/−, referred to as KO) resulted in substantial gut microbiota compositional changes with reduced Firmicutes to Bacteroidetes (F/B) ratios, altered biodiversity, and decreased body weight compared to VIP+/+ (WT) and VIP+/− (HET) littermates (n = 47)
Summary
Vasoactive intestinal peptide (VIP) is a 28 amino acid (AA) molecule. It was originally isolated from swine intestines and found to be vasoactive by dilating arterioles, thereby substantiating its name (Said and Mutt, 1970). VIP was later discovered in the central nervous system, which redirected the field to investigate its role as a neurotransmitter (Said and Rosenberg, 1976). These studies led to the understanding that VIP acts widely as a neurotransmitter/neuromodulator in the central and peripheral nervous systems. VIP is delivered to immune organs by the peripheral nervous system, including the mucosa-associated lymphoid tissues of the gastrointestinal tract (GIT), where it plays a vital role in maintaining homeostasis (Lelievre et al, 2007)
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