Potential Molecular Mechanisms of Alcohol Use Disorder with Non-Coding RNAs and Gut Microbiota for the Development of Superior Therapeutic Application.

Many investigations have evaluated the expression of noncoding RNAs (ncRNAs) as well as their related molecular functions and biological machineries in individuals with alcohol dependence. Alcohol dependence may be one of the most prevailing psychological disorders globally, and its pathogenesis is intricate and inadequately comprehended. There is substantial evidence indicating significant links between multiple genetic factors and the development of alcohol dependence. In particular, the critical roles of ncRNAs have been emphasized in the pathology of mental illnesses, probably including alcohol dependence. In the comprehension of the action of ncRNAs and their machineries of modification, furthermore, they have emerged as therapeutic targets for a variety of psychiatric illnesses, including alcohol dependence. It is worth mentioning that the dysregulated expression of ncRNAs has been regularly detected in individuals with alcohol dependence. An in-depth knowledge of the roles of ncRNAs and m6A modification may be valuable for the development of a novel treatment against alcohol dependence. In general, a more profound understanding of the practical roles of ncRNAs might make important contributions to the precise diagnosis and/or actual management of alcohol dependence. Here, in this review, we mostly focused on up-to-date knowledge regarding alterations and/or modifications in the expression of ncRNAs in individuals with alcohol dependence. Then, we present prospects for future research and therapeutic applications with a novel concept of the engram system.

Enterocloster alcoholdehydrogenati sp. nov., a Novel Bacterial Species Isolated from the Feces of a Patient with Alcoholism.

Strain C5-48T, an anaerobic intestinal bacterium that potentially accumulates acetaldehyde at levels exceeding its minimum mutagenic concentration (50 µM) in the colon and rectum, was isolated from the feces of a patient with alcoholism. The 16S rRNA gene sequence of strain C5-48T showed high similarity to the corresponding sequences of Lachnoclostridium edouardi Marseille-P3397T (95.7%) and Clostridium fessum SNUG30386T (94.7%). However, phylogenetic analysis using the sequences of the 16S rRNA, rpoB, and hsp60 genes and whole-genome analysis strongly suggested that C5-48T should be included in the genus Enterocloster. The novelty of strain C5-48T was further confirmed by comprehensive average nucleotide identity (ANI) calculations based on its whole-genome sequence, which showed appreciable ANI values with known Enterocloster species (e.g., 74.3% and 73.4% with Enterocloster bolteae WAL 16351T and Enterocloster clostridioformis ATCC 25537T, respectively). The temperature range for growth of strain C5-48T was 15-37 °C with an optimum of 37 °C. The pH range for growth was 5.5-10.5 with an optimum of 7.5. The major constituents of the cell membrane lipids of strain C5-48T were 16:0, 14:0, and 18:1 ω7c dimethyl acetal fatty acids. On the basis of the genotypic and phenotypic properties, Enterocloster alcoholdehydrogenati sp. nov. is proposed, with the type strain C5-48T (= JCM 33305T = DSM 109474T).

Microbiome Alterations in Alcohol Use Disorder and Alcoholic Liver Disease.

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.

Restoring an adequate dietary fiber intake by inulin supplementation: a pilot study showing an impact on gut microbiota and sociability in alcohol use disorder patients.

Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composition and to evaluate its effect on gastrointestinal tolerance, metabolism, and patient's behavior. A randomized, double-blind, placebo-controlled study included 50 AUD patients assigned to inulin versus maltodextrin daily supplementation for 17 days. Biological measurements (fecal microbial 16S rDNA sequencing, serum biology), dietary intake, validated psychological questionnaires, and gastrointestinal tolerance assessment were performed before and after the intervention. Inulin significantly decreased the richness and evenness and induced changes of 8 genera (q < 0.1) including Bifidobacterium and Bacteroides. Prebiotic had minor effects on gastrointestinal symptoms and nutritional intakes compared to placebo. All patients showed an improvement in depression, anxiety, and craving scores during alcohol withdrawal regardless of the intervention group. Interestingly, only patients treated with inulin significantly improved the sociability score and had an increased serum level of brain-derived neurotrophic factor. This pilot study shows that inulin is well tolerated and modulates the gut microbiota and the social behavior in AUD patients, without further improving other psychological and biological parameters as compared to placebo. Gut2Brain study, clinicaltrial.gov: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709.

TLR4 Deficiency Affects the Microbiome and Reduces Intestinal Dysfunctions and Inflammation in Chronic Alcohol-Fed Mice.

Chronic alcohol abuse causes an inflammatory response in the intestinal tract with damage to the integrity of the mucosa and epithelium, as well as dysbiosis in the gut microbiome. However, the role of gut bacteria in ethanol effects and how these microorganisms interact with the immune system are not well understood. The aim of the present study was to evaluate if TLR4 alters the ethanol-induced intestinal inflammatory response, and whether the response of this receptor affects the gut microbiota profile. We analyzed the 16S rRNA sequence of the fecal samples from wild-type (WT) and TLR4-knockout (TLR4-KO) mice with and without ethanol intake for 3 months. The results demonstrated that chronic ethanol consumption reduces microbiota diversity and causes dysbiosis in WT mice. Likewise, ethanol upregulates several inflammatory genes (IL-1ß, iNOS, TNF-α) and miRNAs (miR-155-5p, miR-146a-5p) and alters structural and permeability genes (INTL1, CDH1, CFTR) in the colon of WT mice. Our results further demonstrated that TLR4-KO mice exhibit a different microbiota that can protect against the ethanol-induced activation of the immune system and colon integrity dysfunctions. In short, our results reveal that TLR4 is a key factor for determining the gut microbiota, which can participate in dysbiosis and the inflammatory response induced by alcohol consumption.

Integrated Analyses of the Gut Microbiota, Intestinal Permeability, and Serum Metabolome Phenotype in Rats with Alcohol Withdrawal Syndrome.

The etiology of alcohol dependence is not completely understood. Increasing evidence reveals that gut microbiota dysbiosis is associated with certain psychiatric disorders, including alcoholism, through the "microbiota-gut-brain" axis. The aims of this study were to evaluate the effect of alcohol abuse on the gut microbiota, intestinal permeability and serum metabolic profile and to determine whether alcohol-induced alterations in gut microbiota are correlated with gut permeability and serum metabolic phenotype changes. 16S rRNA gene high-throughput sequencing and nontarget metabolomics techniques were applied in an alcohol-dependent rat model in the present study. The results showed that alcohol intake altered the composition and structure of the colonic microbiota, especially the relative abundances of commensal microbes in the families Lachnospiraceae and Prevotellaceae, which were significantly decreased. Alcohol-dependent rats developed gut leakiness and a serum metabolic phenotype disorder. The valine, leucine and isoleucine biosynthesis pathways and arginine and proline metabolism pathways were obviously influenced by alcohol intake. Moreover, alcohol consumption disturbed the brain's neurotransmitter homeostasis. Regression analysis showed that alcohol-induced colonic microbiota dysbiosis was strongly associated with increased intestinal permeability and serum metabolic phenotype and neurotransmitter disorders. These results revealed that gut microbiota dysbiosis and serum metabolite alteration might be a cofactor for developing of alcohol dependence. IMPORTANCE Gut microbiota dysbiosis is associated with certain psychiatric disorders through the "microbiota-gut-brain" axis. Here, we revealed that alcohol consumption induced colonic microbiota dysbiosis, increased intestinal permeability, and altered the serum metabolic phenotype in rats, and there was a strong correlation between gut microbiota dysbiosis and serum metabolite disorders. Thus, gut microbiota dysbiosis and serum metabolite alteration may be a cofactor for development of alcohol dependence.

Long-lasting microbial dysbiosis and altered enteric neurotransmitters in adult rats following adolescent binge ethanol exposure.

Human alcoholism and ethanol exposure of adult mice cause acute microbial dysbiosis. Adolescent binge drinking is common, but the effect of adolescent ethanol exposure on the adult microbiome and enteric neurotransmitters has not been studied. In the current study, male Wistar rats received adolescent intermittent ethanol (AIE) treatment, and fecal samples were collected on postnatal day (P)54 and P95 for bacterial 16S rRNA amplicon sequencing. Cecal tissue was collected on P95 for analysis of innate immune and neurotransmitter marker expression. At the genus level, AIE treatment altered the relative abundance of several microbes, including decreased relative abundance of Dehalobacterium and CF231 (a member of the Paraprevotellaceae family) that persisted into adulthood. Across aging, the relative abundance of several microbes was altered in both control- and AIE-treated rats. At P95, AIE exposure was associated with increased cecal serotonin levels and reduced choline acetyltransferase gene expression. Taxonomic shifts at P54 and at P95 suggest that AIE causes both immediate and lasting microbial dysbiosis. The lasting microbial dysbiosis was accompanied by alterations of enteric neurotransmitters.

Gut Microbiota-Induced Changes in ß-Hydroxybutyrate Metabolism Are Linked to Altered Sociability and Depression in Alcohol Use Disorder.

Patients with alcohol use disorder (AUD) present with important emotional, cognitive, and social impairments. The gut microbiota has been recently shown to regulate brain functions and behavior but convincing evidence of its role in AUD is lacking. Here, we show that gut dysbiosis is associated with metabolic alterations that affect behavioral (depression, sociability) and neurobiological (myelination, neurotransmission, inflammation) processes involved in alcohol addiction. By transplanting the gut microbiota from AUD patients to mice, we point out that the production of ethanol by specific bacterial genera and the reduction of lipolysis are associated with a lower hepatic synthesis of ß-hydroxybutyrate (BHB), which thereby prevents the neuroprotective effect of BHB. We confirm these results in detoxified AUD patients, in which we observe a persisting ethanol production in the feces as well as correlations among low plasma BHB levels and social impairments, depression, or brain white matter alterations.

Pneumonia and alcohol use disorder: Implications for treatment.

Patients with alcohol use disorder (AUD) are at higher risk of pneumonia and of poor outcomes. This article reviews the etiology of pneumonia in patients with AUD, its impact on mortality and resource utilization, and its implications for treatment.

Deficiency of Intestinal α1-2-Fucosylation Exacerbates Ethanol-Induced Liver Disease in Mice.

BACKGROUND: Fucosyltransferase 2 (Fut2)-mediated intestinal α1-2-fucosylation is important in maintaining a symbiotic host-microbiota relationship and can protect against several pathogens. Intestinal dysbiosis is an important factor for the progression of experimental ethanol (EtOH)-induced liver disease, but the role of Fut2 in modulating the intestinal glycocalyx during alcohol-associated liver disease is unknown. We investigated the role of Fut2-mediated intestinal α1-2-fucosylation for the development of alcohol-associated liver disease. METHODS: Immunohistochemistry staining was applied to evaluate α1-2-fucosylation in duodenal biopsies from patients with alcohol use disorder. Wild-type (WT) and Fut2-deficient littermate mice were subjected to Lieber-DeCarli models of chronic EtOH administration and the chronic-binge EtOH diet (NIAAA model). RESULTS: Intestinal α1-2-fucosylation was down-regulated in patients with alcohol use disorder. Lack of α1-2-fucosylation in Fut2-deficient mice exacerbates chronic EtOH-induced liver injury, steatosis, and inflammation without affecting EtOH metabolism. Dietary supplementation of the α1-2-fucosylated glycan 2'-fucosyllactose (2'-FL) ameliorates EtOH-induced liver disease in Fut2-deficient mice in the NIAAA model. Despite no direct effects on growth of Enterococcus faecalis in vitro, intestinal α1-2-fucosylation reduces colonization of cytolysin-positive E. faecalis in the intestine of EtOH-fed mice. CONCLUSIONS: Intestinal α1-2-fucosylation acts as a host-protective mechanism against EtOH-induced liver disease. 2'-FL is an oligosaccharide naturally present in human milk that could be considered as therapeutic agent for alcohol-associated liver disease.

Transplantation of fecal microbiota from patients with alcoholism induces anxiety/depression behaviors and decreases brain mGluR1/PKC ε levels in mouse.

Recent studies have revealed that the gut microbiota participates in the psychiatric behavior changes in disorders associated with alcohol. But it still remains unknown whether alcoholism is involved in changes in gut microbiota and its underlying mechanism is also not clear. Here, we tested the gut microbiota of patients with alcoholism and conducted fecal microbiota transplantation (FMT) from patients with alcoholism to C57BL/6J mice whose gut microbiota had been sharply suppressed with antibiotics (ABX). Then we evaluated their alcohol preference degree, anxiety, and depression-like behaviors and social interaction behaviors, together with molecular changes in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc). Our data indicated that the gut microbiota of patients with alcoholism was drastically different from those of the healthy adults. The abundance of p_Firmicutes was significantly increased whereas p_Bacteroidetes was decreased. Compared to mice transplanted with fecal microbiota from healthy male adults, the mice accepting fecal microbiota from patients with alcoholism showed (a) anxiety-like and depression-like behaviors, (b) decreased social interaction behaviors, (c) spontaneous alcohol preference, and (d) decreased brain-derived neurotrophic factor (BDNF), alpha 1 subunit of GABA type A receptor (α1GABAA R) in mPFC and decreased metabotropic glutamate receptors 1 (mGluR1), protein kinase C (PKC) ε in NAc. Overall, our results suggest that fecal microbiota from patients with alcoholism did induce a status like alcohol dependence in C57BL/6J mice. The decreased expression of BDNF, α1GABAA R, and mGluR1/ PKC ε may be the underlying mechanism.

Changes in the composition of the human intestinal microbiome in alcohol use disorder: a systematic review.

Background: A growing body of evidence highlights the role of the intestine in the development of various alcohol use disorder (AUD) complications. The intestinal microbiome has been proposed as an essential factor in mediating the development of AUD complications such as alcoholic liver disease.Objectives: To provide a comprehensive description of alcohol-induced intestinal microbiome alterations.Methods: We conducted a systematic review of studies investigating the effect of alcohol on the intestinal microbiome using the PRISMA checklist. We searched the Medline database on the PubMed platform for studies determining the effect of alcohol on microbiota in individuals with AUD. The manual search included references of retrieved articles. Only human studies examining the intestinal bacterial microbiome using 16S ribosomal RNA sequencing were included. Data comparing relative abundances of bacteria comprising intestinal microbiota was extracted.Results: We retrieved 17 studies investigating intestinal microbiome alterations in individuals with AUD. Intestinal microbiome alterations in individuals with AUD included depletion of Akkermansia muciniphila and Faecalibacterium prausnitzii and an increase of Enterobacteriaceae. At the phylum level, a higher abundance of Proteobacteria and lower of Bacteroidetes were found. Mixed results regarding Bifidobacterium were obtained. Several species of short-chain fatty acids producing bacteria had a lower abundance in individuals with alcohol use disorder.Conclusion: Intestinal microbiome alterations associated with dysbiosis in individuals with AUD are generally consistent across studies, making it a promising target in potential AUD complications treatment.

Lethal infective endocarditis due to Streptococcus agalactiae in a man with a history of alcohol abuse: A case report.

RATIONAL: Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart, which may include one or more heart valves, the mural endocardium. PATIENT CONCERNS: A 53-years-old man with a history of alcohol abuse was admitted in hospital for fever, paroxysmal atrial fibrillation cardioverted by Amiodarone and pulmonary infection. DIAGNOSIS: A case of recurrent severe endocarditis, with neurological complications both ischemic and hemorrhagic and heart failure caused by Streptococcus agalactiae in healthy man we reported. INTERVENTIONS: Surgery was performed 2 weeks after admission. OUTCOMES: The onset of intracranial hemorrhage delayed second cardiac surgery and the patient died because of end-stage heart failure. CONCLUSIONS: Infective endocarditis caused by S. agalactiae is very rare, particularly in patients without underlying structural heart disease. This study showed that IE due to S. Agalactiae is a disease with high mortality when associated with neurological complication, heart failure but especially when it is recurrent and hits valve prosthesis.

Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease.

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1-3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.

Alcohol or Gut Microbiota: Who Is the Guilty?

Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.

[What is the role of the gut microbiota in the development of alcohol use disorders?] / Troubles liés à l'usage d'alcool : et si l'addiction trouvait son origine dans l'intestin ?

Alcohol addiction is a complex and multifactorial disease influenced by social, psychological and biological aspects. The current pharmacological drugs used in the management of alcohol dependence have shown only a modest efficacy and the relapse rate remains high in this disease. Recently, the gut microbiota, a huge and dynamic ecosystem made up of billions of microorganisms living in our intestine, has been shown to regulate many important functions for human health. Indeed, the gut microbiota is known to influence our metabolism, our immune system as well as our nervous system with consequences for brain functions, mood and behaviour. We have shown that heavy and chronic alcohol consumption induced important changes in the composition of the gut microbiota. Furthermore, the microbial changes are associated with the severity of depression, anxiety and alcohol craving that are important factors predicting the risk of relapse. This suggests the existence of a gut-brain axis in alcohol dependence and supports the development of new therapeutic alternatives, targeting the gut microbiota, in the management of alcohol dependence.

L'addiction à l'alcool est une maladie complexe, impliquant à la fois des facteurs sociaux, psychologiques et biologiques. La prise en charge des patients alcoolo-dépendants est difficile car les médicaments actuels ont une efficacité limitée dans le maintien de l'abstinence, et le taux de rechute reste très élevé. Récemment, le microbiote intestinal, un écosystème constitué de milliards de micro-organismes vivant dans notre intestin, est devenu un acteur clé de la santé humaine. Il est connu pour réguler notre métabolisme, notre système immunitaire, mais également notre système nerveux, et donc notre comportement et notre humeur. Nos études récentes ont montré que la consommation abusive d'alcool entraîne des modifications importantes de la composition du microbiote intestinal. Nous avons également montré que ces altérations microbiennes étaient associées à la sévérité des symptômes de dépression, d'anxiété et d'appétence à l'alcool, suggérant ainsi l'existence d'un dialogue entre l'intestin et le cerveau. Ces résultats encouragent la recherche de nouvelles pistes thérapeutiques, ciblant le microbiote intestinal, dans le traitement de la dépendance à l'alcool.

Characterization of gut microbiota composition and functions in patients with chronic alcohol overconsumption.

Excessive alcohol intake can alter the gut microbiota, which may underlie the pathophysiology of alcohol-related diseases. We examined gut microbiota composition and functions in patients with alcohol overconsumption for >10 years, compared to a control group of patients with a history of no or low alcohol intake. Faecal microbiota composition was assessed by 16S rRNA sequencing. Gut microbiota functions were evaluated by quantification of short-chain fatty acids (SCFAs) and predictive metagenome profiling (PICRUSt). Twenty-four patients, mean age 64.8 years (19 males), with alcohol overconsumption, and 18 control patients, mean age 58.2 years (14 males) were included. The two groups were comparable regarding basic clinical variables. Nutritional assessment revealed lower total score on the screening tool Mini Nutritional Assessment, lower muscle mass as assessed by handgrip strength, and lower plasma vitamin C levels in the alcohol overconsumption group. Bacteria from phylum Proteobacteria were found in higher relative abundance, while bacteria from genus Faecalibacterium were found in lower relative abundance in the group of alcohol overconsumers. The group also had higher levels of the genera Sutterella, Holdemania and Clostridium, and lower concentration and percentage of butyric acid. When applying PICRUSt to predict the metagenomic composition, we found that genes related to invasion of epithelial cells were more common in the group of alcohol overconsumers. We conclude that gut microbiota composition and functions in patients with alcohol overconsumption differ from patients with low consumption of alcohol, and seem to be skewed into a putative pro-inflammatory direction.

The gut microbiota: A new target in the management of alcohol dependence?

The gastrointestinal tract is the natural habitat for a huge community of microorganisms, comprising bacteria, viruses, fungi and yeast. This microbial ecosystem codevelops with the host throughout life and is subject to a complex interplay that depends on multiple factors including host genetics, nutrition, life-style, stress, diseases and antibiotics use. The gut microbiota, that refers to intestinal bacteria, has profound influence on the host immune system, metabolism and nervous system. Indeed, intestinal bacteria supply the host with essential nutrients such as vitamins, metabolize bile acids and undigested compounds, defend against pathogen invasion, participate to the development of the intestinal architecture and the intestinal immune system and play an important role in the maintenance of the gut barrier function. More recently, the gut microbiota has been shown to influence brain functions, such as myelin synthesis, the blood-brain barrier permeability and neuroinflammatory responses but also mood and behavior. The cross-talk between microbes and the host implicates a vast array of signaling pathways that involve many different classes of molecules like metabolites produced by the bacteria from dietary or endogenous sources of carbohydrates and proteins (i.e. short-chain fatty acids (SCFAs), indole), neurotransmitters and inflammatory cytokines. This review will focus on the involvement of the gut microbiota in the pathophysiological aspects of alcohol dependence related to the gut barrier function, liver damage and psychological disturbances. We will also discuss the possibility to create new and realistic humanized animal models of alcohol dependence by the use of fecal transplantation.

Comparison of Microbial Diversity and Composition in Jejunum and Colon of the Alcohol-dependent Rats.

Alcohol dependence is a global public health problem, yet the mechanisms of alcohol dependence are incompletely understood. The traditional view has been that ethanol alters various neurotransmitters and their receptors in the brain and causes the addiction. However, an increasing amount of experimental evidence suggests that gut microbiota also influence brain functions via gut-to-brain interactions, and may therefore induce the development of alcohol use disorders. In this study, a rat model of alcohol dependence and withdrawal was employed, the gut microbiota composition was analyzed by high-throughput 16S rRNA gene sequencing, and the metagenome function was predicted by PICRUSt software. The results suggested that chronic alcohol consumption did not significantly alter the diversity and richness of gut microbiota in the jejunum and colon, but rather markedly changed the microbiota composition structure in the colon. The phyla Bacteroidetes and eight genera including Bacteroidales S24-7, Ruminococcaceae, Parabacteroides, Butyricimonas, et al were drastically increased, however the genus Lactobacillus and gauvreauii in the colon were significantly decreased in the alcohol dependence group compared with the withdrawal and control groups. The microbial functional prediction analysis revealed that the proportions of amino acid metabolism, polyketide sugar unit biosynthesis and peroxisome were significantly increased in the AD group. This study demonstrated that chronic alcohol consumption has a dramatic effect on the microbiota composition structure in the colon but few effects on the jejunum. Inducement of colonic microbiota dysbiosis due to alcohol abuse seems to be a factor of alcohol dependence, which suggests that modulating colonic microbiota composition might be a potentially new target for treating alcohol addiction.