Sodium Butyrate Supplementation Modulates Neuroinflammatory Response Aggravated by Antibiotic Treatment in a Mouse Model of Binge-like Ethanol Drinking

Abstract

Growing evidence supports the pivotal role of the bidirectional interplay between the gut microbiota and the central nervous system during the progression of alcohol use disorder (AUD). In our previous study, supplementation with sodium butyrate (SB) in C57BL/6J mice prevented increased ethanol consumption in a binge-like drinking paradigm (DID) as a result of treatment with a non-absorbable antibiotic cocktail (ABX). In this study, we tested the hypothesis that SB protection against enhanced ABX-induced ethanol consumption in mice is partially due to modulation of neuroinflammatory responses. Pro- and anti-inflammatory cytokines, as well as changes in microglia and astrocytes were analyzed in hippocampus tissues from ABX-, SB-, ABX+SB-treated mice subjected to 4-week DID. We found that ethanol without or with ABX treatment increased mRNA levels of key brain cytokines (MCP-1, TNF-α, IL-1β, IL-6 and IL-10) while SB supplementation prevented these changes. Additionally, SB supplementation prevented changes in microglia, i.e., increase in Iba-1 positive cell number and morphology, and in astrocytes, i.e., decrease in GFAP-positive cell number, induced by combination of ethanol and ABX treatments. Our results suggest that gut microbiota metabolites can influence drinking behavior by modulation of neuroinflammation, highlighting the potential for microbiome-targeting strategies for treatment or prevention of AUD.

Tributyrin Intake Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm in LDLR-/- Mice

“…We found that tributyrin reduced inflammation and macrophage infiltration in the aortic wall of AAA model mice, as evidenced by the decreased expression of plasminogen, CD11b-positive cells, CD36-positive cells, and F4/80-positive cells. This is consistent with previous studies indicating that butyrate has anti-inflammatory effects due to inhibiting the activation of nuclear factor kappa B (NF-κB) and suppressing the production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) [61][62][63][64][65]. A variety of inflammatory cell processes occur during aortic wall inflammation, including mononuclear cell infiltration, immunoglobulin secretion, and cytokine production, suggesting that both innate and adaptive immune responses are involved [66].…”

Baseline gut microbiome and metabolites are correlated with alcohol consumption in a zonisamide clinical trial of heavy drinking alcoholic civilians

“…[11][12][13][14][15][16][17] During periods of heavy alcohol consumption, the production of short-chain fatty acids (SFCAs) are significantly decreased. 11,16,18 These microbially-produced SCFAs influence various biological processes such as depression, anxiety, and craving, [19][20][21][22][23] which are common comorbidities of AUD. Further, the administration of SCFAs has been shown to reduce drinking behavior in rodent models.…”

“…Further, the administration of SCFAs has been shown to reduce drinking behavior in rodent models. [23][24][25][26] The microbiome and its metabolites are not only responsive to alcohol consumption but also able to influence drinking behavior. The AUD-associated gut microbiome has been linked to increased alcohol consumption, 27,28 depression, anxiety, alcohol craving, and possibility of relapse.…”

“…27 Fecal microbiota transplantation from healthy donors without AUD to patients with AUD has proven to be a promising route for treatment of AUD and AUD-associated health problems. 23,29 The baseline gut microbiome has been found to play an important role in response to cancer therapy, 31 nutritional intervention 32 and efficacity of SARS-CoV-2 vaccines. 33,34 However, whether the importance of baseline gut microbiome in alcohol drinking behavior in AUD patients undergoing treatment has not been investigated.…”

“…27 Fecal microbiota transplantation from healthy donors without AUD to patients with AUD has proven to be a promising route for treatment of AUD and AUD-associated health problems. 23,29…”