Mice that switched from a high sugar/butter diet to a standard diet developed a strong preference for alcohol over water, in a study exploring the connection between gastrointestinal microorganisms and alcohol use disorder (AUD). The findings, published in the journal Alcohol, Clinical and Experimental Research, may help lead to new treatments for AUD.
Gut microbiota help maintain health, contributing to essential processes including immunity and metabolism. Gut microbiota maintain bidirectional communication with the brain via the gut-brain axis, such that a disturbance in one is linked to changes in the other. Studies involving animals and humans point to a highly complex relationship between microbiota disruption, metabolism, and alcohol use.
Investigators in Brazil and France initially fed mice a high sugar/butter diet, then switched them to a standard diet. Those mice developed a strong preference for alcohol over water, suggesting that withdrawal of the high sugar/butter diet affected their reward system, triggering addiction-like behavior. In contrast, mice consistently fed either a standard diet or a high sugar/butter diet remained averse to alcohol or neutral.
The mice that turned to alcohol were found to have a distinct colonic microbiota composition. Alterations in bacterial diversity and abundance were connected with unusual metabolite production and neurobiological pathways. Gut microbiota contribute to amino acid metabolism, in turn influencing systemic metabolism and neurotransmission.
In mice with a strong alcohol preference, amino acid metabolism waned. The effects included reduced levels of an amino acid that contributes to the alcohol reward system, and diminished production of short-chain fatty acids, which help regulate alcohol preferences. The reduction in butyrate, for example, an anti-inflammatory molecule that helps regulate appetite and alcohol craving, may indicate increased vulnerability to compulsive drinking.
Another bacterium, implicated in metabolic illness and addictive behaviors, became more prevalent. Secondary bile-acid synthesis also increased, potentially contributing to increased inflammation and intestinal permeability—two conditions associated with AUD. The researchers also observed changes in oxidative stress and dopamine metabolism that could raise the risk for alcohol-seeking behavior and excess drinking.
The findings highlight the role of gut microbiota in modulating amino acid metabolism and systemic metabolism, affecting multiple neurobiological mechanisms involved in vulnerability to (or resilience against) alcohol dependence. The metabolites derived from gut microbiota are potential therapeutic targets for AUD.
More information:
Mírian Velten Mendes et al, Predicted functional alterations in colonic microbiota metabolism underlie ethanol consumption and preference behavior in mice, Alcohol, Clinical and Experimental Research (2025). DOI: 10.1111/acer.70165
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