Microbiome Alterations in Alcohol Use Disorder and Alcoholic Liver Disease

Abstract

Microbiome alterations are emerging as one of the most important factors that influence the course of alcohol use disorder (AUD). Recent advances in bioinformatics enable more robust and accurate characterization of changes in the composition of the microbiome. In this study, our objective was to provide the most comprehensive and up-to-date evaluation of microbiome alterations associated with AUD and alcoholic liver disease (ALD). To achieve it, we have applied consistent, state of art bioinformatic workflow to raw reads from multiple 16S rRNA sequencing datasets. The study population consisted of 122 patients with AUD, 75 with ALD, 54 with non-alcoholic liver diseases, and 260 healthy controls. We have found several microbiome alterations that were consistent across multiple datasets. The most consistent changes included a significantly lower abundance of multiple butyrate-producing families, including Ruminococcaceae, Lachnospiraceae, and Oscillospiraceae in AUD compared to HC and further reduction of these families in ALD compared with AUD. Other important results include an increase in endotoxin-producing Proteobacteria in AUD, with the ALD group having the largest increase. All of these alterations can potentially contribute to increased intestinal permeability and inflammation associated with AUD and ALD.

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

“…Individuals with AUD are often reported to have lower alpha diversity as compared with healthy controls 46,47 but this is not always the case. 17,27 There is even less consensus on the relationship between AUD severity and alpha diversity.…”

“…Both acute and chronic alcohol consumption are linked to a shift in microbiome composition favoring an overrepresentation of proinflammatory microbes and an underrepresentation of short-chain fatty acid-producing microbes. [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.…”

Dangers of the chronic stress response in the context of the microbiota-gut-immune-brain axis and mental health: a narrative review

“…Alcohol use disorder (AUD) is one of the most significant preventable contributors to morbidity and mortality ( 59 , 60 ). Alcohol directly alters the permeability of the intestinal barrier, causes dysbiosis, and is associated with peripheral and central inflammation ( 60 ).…”

“…found that individuals with AUD demonstrated lower abundance of Akkermansia muciniphilia and Faecalibacterium prausnitzii , less of the genus Bacterioides, at the phylum level more Pseudomonadota (formerly Proteobacteria), and more members of the Enterobacteriaceae family ( 61 ). A recent study by Litwinowicz & Gamian compared the microbiomes of participants with AUD, alcoholic liver disease (ALD), and healthy controls ( 59 ).…”

Gut microbiome in alcohol use disorder: Implications for health outcomes and therapeutic strategies-a literature review

“…A metagenomic analysis in AUD patients by Litwinowicz et al [ 55 ] (concluded to a significant increase in facultative anaerobes (such as the Enterobacteriaceae family), that may be a result of a simultaneous decrease in levels of butyrate-producing bacteria (Butyricicoccaceae, Lachnospiraceae, Ruminococcaceae, Oscillospiraceae), thus reducing beta-oxidation, which in turn ends up increasing oxygen levels. Most of the produced butyrate gets used up for energy, with only approximately 5% remaining in circulation, however, this small fraction appears to be capable of inducing a potent anti-inflammatory response, through various pathways, including through the G-protein-coupled receptors 41 and 43[ 56 ], inhibition of IFN-γ signaling, and induction of nuclear factor kappaB[ 57 ].…”