Colonic microbiome is altered in alcoholism

Abstract

Several studies indicate the importance of colonic microbiota in metabolic and inflammatory disorders and importance of diet on microbiota composition. The effects of alcohol, one of the prominent components of diet, on colonic bacterial composition is largely unknown. Mounting evidence suggests that gut-derived bacterial endotoxins are cofactors for alcohol-induced tissue injury and organ failure like alcoholic liver disease (ALD) that only occur in a subset of alcoholics. We hypothesized that chronic alcohol consumption results in alterations of the gut microbiome in a subgroup of alcoholics, and this may be responsible for the observed inflammatory state and endotoxemia in alcoholics. Thus we interrogated the mucosa-associated colonic microbiome in 48 alcoholics with and without ALD as well as 18 healthy subjects. Colonic biopsy samples from subjects were analyzed for microbiota composition using length heterogeneity PCR fingerprinting and multitag pyrosequencing. A subgroup of alcoholics have an altered colonic microbiome (dysbiosis). The alcoholics with dysbiosis had lower median abundances of Bacteroidetes and higher ones of Proteobacteria. The observed alterations appear to correlate with high levels of serum endotoxin in a subset of the samples. Network topology analysis indicated that alcohol use is correlated with decreased connectivity of the microbial network, and this alteration is seen even after an extended period of sobriety. We show that the colonic mucosa-associated bacterial microbiome is altered in a subset of alcoholics. The altered microbiota composition is persistent and correlates with endotoxemia in a subgroup of alcoholics.

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

“…Dysbiosis was reported in only a subset of patients with alcohol use disorder (AUD) who showed lower and higher median abundances of Bacteroidetes and Proteobacteria, respectively, such that microbial alterations correlated with elevated serum endotoxin levels (Mutlu et al, 2012). Alterations in microbial composition were not correlated to the duration of sobriety, suggesting alcohol-related dysbiosis is long-lasting and persists despite abstinent periods (Mutlu et al, 2012), though abstinence was measured primarily via self-report assessments. Chronic alcohol consumption can also induce bacterial overgrowth in the small intestine, mucosal damage in the large intestine, and subsequent elevations in intestinal permeability (Keshavarzian et al, 2009).…”

“…By checking auto-Ab levels and sequence homology comparisons between ED and healthy participants, the studies reviewed support the possibility that gut microbiota-driven dysregulation of neuroendocrine control of appetite leads to behavioral profiles associated with food intake in patients with EDs. With respect to AUD, chronic alcohol use induces dysbiosis and increased intestinal permeability in only a subset of alcohol dependent patients (Bode and Bode, 2003;Mutlu et al, 2012), allowing microbial metabolites to enter peripheral and central circulation and impact behavioral correlates such as alcohol craving (Leclercq et al, 2014b). Thus, chronic excessive alcohol use is necessary, but not sufficient to cause gut dysfunction in alcohol dependent patients (Mutlu et al, 2012;Leclercq et al, 2014b).…”

“…irritable bowel disease, colorectal cancer and diabetes (Kim et al, 2013). Gut dysbiosis is associated with damages to the intestinal barrier, which negatively impacts the host's ability to respond to stressors (Mutlu et al, 2012).…”

Taurocholic acid metabolism by gut microbes and colon cancer

“…Intriguingly, each of these factors also alters the gut microbiome. 4,5 Several studies have attempted to apply high-throughput sequencing followed by network correlation analysis to identify gut bacteria associated with colorectal tumors. [6][7][8][9][10][11] While each study concluded that CRC is associated with gut dysbiosis, a significant shift in the gut microbiome community structure relative to healthy control populations, there has been a lack of consistently observed dysbiotic microbiota patterns.…”

Probiotics and Liver Disease

“…18 A study in human subjects confirmed these findings and also indicated a correlation between alcohol-induced dysbiosis and endotoxemia. 19 Recent animal studies have shown that microbial translocation begins early in the course of alcoholic liver disease, leading to increased inflammation and eventually cirrhosis. 20 In rat models of hepatocarcinogenesis, induction of gut dysbiosis significantly promoted carcinogenesis.…”