In a study recently published in the journal PLoS ONE, researchers investigated the impact of alcohol consumption and short-term abstinence on gut microbiota dysbiosis in patients with alcohol use disorder (AUD). In their case-control study, they assessed the gut microbiota and metabolome of three cohorts: newly abstinent individuals, current drinkers, and BMI-matched healthy controls.
Surprisingly, the findings revealed that AUD patients who sought treatment for their illness and abstained from alcohol consumption for at least 6 weeks displayed the most distinctive gut microbiota and metabolome composition, with significantly higher lipid superpathway-derived metabolites than the other two cohorts. In contrast to previous studies that noted improvements in gut microbiota after abstinence, the current study highlights the potential long-term effects of alcohol abuse, despite short-term abstinence. Furthermore, abstinence was found to be associated with significantly higher psychological distress compared to currently drinking AUD participants.
What is AUD and what do we know about it?
Alcohol use disorder (AUD) is a chronic behavioral disorder characterized by uncontrolled alcohol consumption due to emotional and physical dependence on alcohol. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines the disorder as “a problematic pattern of alcohol use that leads to clinically significant impairment or distress,” and this umbrella term includes both excessive drinking (four or more drinks within two hours or a blood alcohol content above 0.08%) and binge drinking (eight or more drinks per week).
Alarmingly, the prevalence of AUD is on the rise worldwide, with an estimated average prevalence of 5.1% worldwide and over 10.2% in developed countries such as the United States. AUD is associated with a range of mental disorders, including depression, socio-emotional disorders, psychosis, and anxiety disorders. The physical effects of long-term alcohol consumption are also well documented, including cancer, fetal alcohol syndrome, and more recently, gut dysbiosis. It has been observed that damage to the intestinal mucosa increases intestinal permeability and, in extreme cases, releases toxins into the circulatory system, ultimately causing severe damage to the liver.
Previous literature investigating the effects of abstinence in individuals seeking anti-AUD interventions has reported mostly positive findings, but study methods have often been based on participants' recollections, confounding the results.
“…contributing to intra- and inter-individual heterogeneity, including failure to take into account lifestyle and environmental factors known to influence gut bacteria. In addition to retrospective measurements of alcohol consumption, which are subject to recollection bias and the tightly controlled inpatient environment, failure to properly account for these factors may prevent researchers from making definitive conclusions about whether dysbiosis and metabolic changes are due to abstinence, factors specific to inpatient care (e.g., diet, controlled environment), or other factors.”
About the Research
The aim of this study is to compare the gut microbiota and metabolome across three cohorts: 1. Abstinent drinkers (AB, N = 10) comprised of AUD patients undergoing addiction intervention and abstaining from alcohol for a minimum of 6 weeks; 2. Current drinkers (CD, N = 9) comprised of DSM-5 confirmed AUD patients not undergoing intervention and drinking normally; and 3. Healthy controls (HC, N = 12) with no current or past history of AUD and matched to AB and CD cohort participants for age, sex, body mass index (BMI), and race. Alcohol consumption was measured in drinks per week (binge drinking) or drinks per 2 h (binge drinking), assuming 14 g of alcohol per drink.
Schematic of study design. Abstinent patients with AUD (AB) were enrolled in the study after ≥4 weeks of inpatient treatment (NIH/NIAAA treatment protocol 14-AA-0181) followed by ≥2 weeks of “real-life” (normal life). Non-treatment-seeking, currently drinking AUD (CD) patients and matched healthy controls (HC) were also enrolled. Fecal samples were collected from study participants and processed for gut microbiota and metabolome analysis. Physical examinations, 12-lead electrocardiograms, vital signs measurements, and laboratory tests were performed. Information on physical and mental health (including information on medical conditions and medications) and dietary intake was collected and analyzed. Transient liver elastometry and gastrointestinal permeability tests were performed.
Data collection consisted of participants' socioeconomic, demographic, and medical health records. In addition, alcohol-related clinical characteristics (e.g., severity of AUD), mental health, and psychopathology features were assessed both at study baseline (in-person clinical evaluation) and at frequent follow-ups. Questionnaires such as the Penn Alcohol Craving Scale (PACS), Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar), and Alcohol Use Disorders Identification Test (AUDIT) were used to collate the data provided by participants.
Transient liver elastography was used to identify and diagnose hepatic steatosis and fibrosis. Gastrointestinal permeability tests were performed to assess the integrity of the intestinal mucosa. Fecal samples (collected at the start of the study and at final follow-up) were used for microbiome and metabolome analysis, and the microbiome was performed by 16S rRNA sequencing.
Findings and Conclusions
In contrast to previous studies and the researchers' hypotheses, our results revealed that short-term abstinence in former AUD patients not only did not improve gut microbial health, but instead demonstrated greater gut microbial disruption than current AUD patients who continued to drink normally. Furthermore, individuals in the AB cohort were found to have increased anxiety and depression and poorer sleep quality than either CD or HC, although it was not possible to distinguish whether the underlying causes of these findings were alcohol withdrawal symptoms or the physical effects of abrupt abstinence.
“…we hypothesized that there would be similarities in the gut microbiota/metabolome between healthy controls and newly abstinent people with AUD, but that the CD group would be distinct from the other two groups. In contrast, it was the AB group that stood out from the other two groups in terms of gut microbiota/metabolome.”
Gut microbiota and metabolome analyses revealed that participants in the AD cohort experienced a depletion of beneficial microbial groups (e.g., Akkermansia, Lachnospira, Roseburia, Fusicatenibacter, Lachnospiraceae_UCG_001). In CD and HC participants, the abundance of these gut microbiota remained more or less constant. Similarly, both univariate and multivariate analyses revealed that the fecal metabolome of AB significantly differed from the other two groups in at least 33 identified metabolites, all of which are mainly related to lipid and amino acid pathways.
“Consistent with the above conclusions, the AB group reported being affected by significantly more medical conditions and therefore taking significantly more medications than the other groups. These findings suggest that the differences in gut microbiota and metabolome observed in AB individuals compared to CD and HC may be due to a higher prevalence of diseases and higher medication intake in the AB group.”
In summary, this study highlights that short-term abstinence from chronic heavy or excessive drinking may worsen rather than ameliorate the long-term negative effects of AUD. Further research is needed to see whether these negative effects are gradually or eventually reversed with long-term abstinence, but given the currently available information, your best bet is to quit bad habits (here, frequent or excessive drinking) before they lead to addiction.
Journal References:
Piacentino, D., Vizioli, C., Barb, JJ, Grant-Beurmann, S., Bouhlal, S., Battista, JT, Jennings, O., Lee, MR, Schwandt, ML, Walter, P., Henderson, WA, Chen, K., Turner, S., Yang, S., Fraser, CM, Farinelli, LA, Farokhnia, M., & Leggio, L. (2024). Gut microbial diversity and functional characteristics of patients with alcohol use disorder: a case-control study. JJ Loor (Ed.), PLOS ONE (Vol. 19, No. 6, p. e0302195). Public Library of Science (PLoS), DOI – 10.1371/journal.pone.0302195, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0302195
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