Niacin modulates depressive-like behavior in experimental colitis through GPR109A-dependent mechanisms

Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

“…In addition, a “leaky gut” and increased LPS translocation have also been reported in individuals with MDD [ 225 ]. Data from animal models of colitis have also supported the close relationship between gut inflammation and mood [ 226 , 227 , 228 ]. For example, Yoo et al [ 227 ] showed that fecal microbiota transplantation (FMT) from patients with IBD (Crohn’s disease and ulcerative colits) plus MDD caused depressive-like behaviors in mice, while also increasing peripheral, colonic, and hippocampal levels of corticosterone, IL-1 β, IL6, LPS, and decreasing IL-10 levels.…”

“…In addition, administration of Lactobacillus plantarum NK151, Bifidobacterium longum NK173, and Bifidobacterium bifidum NK175 alleviated depression-like behaviors induced by FMT from IBD plus depression patients, while also normalizing hippocampal NF-κB + Iba1 + cell numbers, IL-1β and IL-6 expression, serum levels of LPS, IL-6, and creatinine, as well as colonic NF-κB + CD11c + cell numbers and IL-1β and IL-6 expression in these mice [ 218 ]. Other preclinical studies have also evaluated colitis and the occurrence of depressive-like behaviors in dextran sulfate sodium (DSS)-treated mice [ 226 , 228 ]. Takashi et al [ 226 ] show that DSS-treated mice presented higher TNF-α and IL-6 expression in the rectum and hippocampus, activated caspase-3 in the hippocampus, as well as decreasing hippocampal neurogenesis, and these changes were reversed by administration of Enterococcus faecalis 2001, which also prevented the occurrence of DSS-induced depressive-like behaviors.…”

“…Takashi et al [ 226 ] show that DSS-treated mice presented higher TNF-α and IL-6 expression in the rectum and hippocampus, activated caspase-3 in the hippocampus, as well as decreasing hippocampal neurogenesis, and these changes were reversed by administration of Enterococcus faecalis 2001, which also prevented the occurrence of DSS-induced depressive-like behaviors. In a more recent study, Wadie et al [ 228 ] showed that niacin ameliorated DSS–induced behavioral deficits, alleviated macroscopic and microscopic colonic inflammatory changes, restored BBB integrity through enhancement of ZO-1, occludin, and claudin-5 protein levels in the hippocampus, while also decreasing IL-1β and NF-kB levels and increasing glutathione (GSH), sirtuin-1 (Sirt-1), nuclear factor erythroid 2–related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) concentrations in the hippocampus. Furthermore, 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis was shown to activate NF-kB, increase gut permeability, fecal and blood levels of LPS, and the number of Enterobacteriaceae (particularly Escherichia coli ) in the gut microbiota in mice.…”

Microbiota-Induced Epigenetic Alterations in Depressive Disorders Are Targets for Nutritional and Probiotic Therapies

“…Activation of GPR109A by niacin or butyrate suppresses colonic inflammation [165]. For example, Wadie et al reported that the neuroprotective effect of niacin against dextran sulfate sodium-induced depressive-like behavior is mediated via GPR109A-mediated mechanisms [166]. Niacin could also reduce oxidative stress and inflammation and enhance hippocampal levels of occludin, ZO-1, and claudin-5 proteins, suggesting niacin is capable of restoring the BBB integrity [166].…”

“…For example, Wadie et al reported that the neuroprotective effect of niacin against dextran sulfate sodium-induced depressive-like behavior is mediated via GPR109A-mediated mechanisms [166]. Niacin could also reduce oxidative stress and inflammation and enhance hippocampal levels of occludin, ZO-1, and claudin-5 proteins, suggesting niacin is capable of restoring the BBB integrity [166]. Moreover, it has been found that 14-day treatment with niacin and butyrate significantly influenced vitamin B12, vitamin B1, vitamin B2, and nicotinamide and increased the abundance of butyrate-producing bacteria, including Firmicutes, Lactobacillaceae, and Lactobacillus in weaned piglets [167].…”