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ABSTRACT Alcohol intake causes many diseases including neuropsychiatric symptoms, nutritional deficiency, progressive pancreatitis, liver cirrhosis, and ischemic heart disease. The gut microbiota changes significantly after alcohol exposure. Alcohol consumption tends to increase in underage and young people, but the feature of the gut microbiota in puberty remains largely unexplored. In this study, we conducted alcohol-exposed pubertal and adult mice model to investigate the intestinal damage and gut microbiota change. Interestingly, the responses of pubertal mice and adult mice after alcohol exposure were different. We found that alcohol dehydrogenase decreased and aldehyde dehydrogenase increased in the liver of pubertal mice, thus reducing the accumulation of toxic acetaldehyde. Furthermore, alcohol exposure caused less intestinal injury in pubertal mice. Through the analysis of metagenome assembly genome, we obtained many unrecognized bacterial genomes. Limosillactobacillus reuteri (cluster_56) and Lactobacillus intestinalis (cluster_57) were assembled from the samples of pubertal mice, which were involved in the production of indole acetic acid and the transformation of bile acids in response to alcohol exposure. This study provided a new insight to investigate the gut microbiota change and explained the difference of the gut microbiota after alcohol exposure between pubertal mice and adult mice.IMPORTANCEThis study elucidates the significant impact of alcohol exposure on the gut microbiota and metabolic pathways in mice, highlighting the differential responses between adolescent and adult stages. Alcohol exposure was found to damage the intestinal barrier, alter the microbial composition by decreasing beneficial bacteria like Lactobacillus, and increase harmful bacteria such as Alistipes. The study also discovered unique microbial changes and resilience in pubertal mice. Species-level metagenomic analysis revealed specific microbial taxa and metabolic functions affected by alcohol. Metagenome-assembled genomes (MAGs) found many species that could not be annotated by conventional methods including many members of Lachnospiraceae, greatly expanding our understanding of the gut microbiota composition. These findings underscore the need for further research on alcohol’s effects on various organs and the implications of microbial metabolites on disease progression.

Abstract Bipolar disorder (BD) is a complex psychiatric disorder characterized by dysfunctions in three domains including emotional processing, cognitive processing, and psychomotor dimensions. However, the neural underpinnings underlying these clinical profiles are not well understood. Based on the reported data, we hypothesized that (i) the core neuropathology in BD is damage in fronto-limbic network, which is associated with emotional dysfunction; (ii) changes in intrinsic brain network, such as sensorimotor network, salience network, default-mode network, central executive network are associated with impaired cognition function; and (iii) beyond the dopaminergic-driven basal ganglia-thalamo-cortical motor circuit modulated by other neurotransmitter systems, such as serotonin (subcortical–cortical modulation), the sensorimotor network and related motor function modulated by other non-motor networks such as the default-mode network are involved in psychomotor function. In this review, we propose a neurocircuit-based clinical characteristics and taxonomy to guide the treatment of BD. We draw on findings from neuropsychological and neuroimaging studies in BD and link variations in these clinical profiles to underlying neurocircuit dysfunctions. We consider pharmacological, psychotherapy, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions in BD. Finally, it is suggested that the methods of testing the neurocircuit-based taxonomy and important limitations to this approach should be considered in future.