Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice

Abstract

The gut microbiota includes a community of bacteria that and play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (Shannon and Simpson index, p<0.05) and beta (ANOSIM, p<0.001) diversity, with a notable decrease in alpha diversity in CIE. These results demonstrate that CIE exposure markedly alters the gut microbiota in mice. Significant increases in genus Alistipes (p<0.001) and significant reductions in genra Clostridium IV and XIVb (Kruskal-Wallis, p<0.001), Dorea (Kruskal-Wallis, p<0.01), and Coprococcus (Kruskal-Wallis, p<0.01) were seen between CIE mice and Control. These findings support the viability of the CIE method for studies investigating the microbiota-gut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress.

A potential role for the gut microbiome in substance use disorders

“…2. Preclinical Literature-Consistent with the clinical literature, preclinical studies in rodent models of alcohol abuse also indicate that alcohol induces gut dysbiosis, though the exact microbial communities that are altered varies from study to study-likely due to differences in alcohol administration regimen as well as concomitant liver disease (Mutlu et al 2009;Yan et al 2011;Bull-Otterson et al 2013;Zhang et al 2015;Peterson et al 2017;Samuelson et al 2017;Xiao et al 2018;Xu et al 2018;Zallar et al 2019). For instance, one group found that chronic alcohol feeding in mice resulted in decreased relative abundance of both Bacteroidetes and Firmicutes as well as an increased relative abundance of Proteobacteria and Actinobacteria in stool samples (Bull-Otterson et al 2013).…”

“…To control for confounding effects of inconsistent alcohol dose resulting of variable food consumption amongst subjects, Peterson et al (2017) instead investigated the effects of chronic intermittent vaporized alcohol (CIE) exposure on the composition of the gut microbiome in C57BL/6J mice. They found an overall decrease in alpha diversity in the CIE mice.…”

Gut microbiome correlates with altered striatal dopamine receptor expression in a model of compulsive alcohol seeking

“…Caecum was collected following three months of abstinence under aseptic conditions and snap-frozen on dry ice. Protocols for microbiome sequencing were used as previously described (Peterson et al, 2017…”

“…Although the source of this neuroinflammation is not yet understood, growing evidence suggests that alterations in microbiota composition may contribute to neuroimmune processes and peripheral inflammation (de Timary et al, 2015;Gorky and Schwaber, 2016;Rea et al, 2016). Changes in the gut microbiome have been reported in both human alcoholic individuals and murine models of chronic alcohol exposure, with increased intestinal permeability (causing endotoxin to escape into the circulation and impact the host), increased abundance of pro-inflammatory gut microbes, like Proteobacteria species, and decreased abundance of normal commensal bacteria like Bacteroidetes (Bull-Otterson et al, 2013;Leclercq et al, 2017;Mutlu et al, 2012;Peterson et al, 2017).…”

The Microbiota, the Gut and the Brain in Eating and Alcohol Use Disorders: A ‘Ménage à Trois’?

“…Although gut microbial alterations related to chronic alcohol use are supported, the mechanism of action is still unclear (Vassallo et al, 2015). A recent preclinical study evaluating the effect of vaporized ethanol administration in mice demonstrated elevated alpha diversity, significantly increased Alistipes genus, and significantly diminished genra Clostridium IV and XIVb, Dorea, and Coprococcus between mice exposed to ethanol vapor and controls (Peterson et al, 2017). Additionally, current understandings of the effect of drugs abuse on the gut microbiota are sparse, although differences have been demonstrated between the commensal gut microbiota of cocaine users and control subjects (Volpe et al, 2014).…”