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However, it remains unclear whether the brain or gut responds first to alcohol exposure. We hypothesized that brain regions respond to alcohol first, preceding changes in the gut microbiome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>B6 mice were given ethanol (EtOH; 5\u2009g\/kg\/day, 42%v\/v, i.g.) at various time points. Fecal samples were collected prior to the first EtOH injection (Day 0), at 24\u2009h following the first, second, and third injections (Day 1, Day 2, and Day 3, respectively), and at 96\u2009h after the third injection (Day 6). Brain regions, central amygdala (CeA), hypothalamus (Hyp), and nucleus accumbens (NAc) were isolated at 2 min, 12\u2009h, 24\u2009h, and 192\u2009h following the first and third doses of binge EtOH, respectively. mRNA or protein expression levels of TNF\u2010\u03b1, IL\u20101\u03b2, P2Y12, ITG\u03b22, and \u03b17nAChR were analyzed by qRT\u2010PCR and western blot, respectively. Fecal microbial composition and abundance were assessed using 16S rRNA metagenomic sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Data revealed increased TNF\u2010\u03b1 expression in the Amg, Hyp, and NAc and increased IL\u20101\u03b2 expression in the Amg and NAc, 12\u2009h after the first EtOH injection. \u03b17nAChR expression in the CeA, Hyp, and NAc was also upregulated at 24\u2009h after the third EtOH dose, compared to the control group. \u03b17nAChR expression in the Hyp was observed at 2\u2009min after the first EtOH dose. CHRNA7 mRNA levels were upregulated 24\u2009h after the third EtOH dose. ITG\u03b22 showed an increasing trend in the Amg at 12\u2009h after the first dose, followed by a significant reduction at 24\u2009h, and 192\u2009h after the third dose. 16S rRNA sequencing revealed a significant difference in \u03b2\u2010diversity on Day 6. The relative abundance of the\n                      <jats:italic>Prevotellaceae<\/jats:italic>\n                      family was higher in EtOH\u2010treated mice compared to controls at Day 3 and Day 6.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study showed that brain inflammation, indicated by \u03b17nAChR upregulation, occurred before EtOH\u2010induced gut dysbiosis, supporting an anterograde sequence of events.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70210","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T04:53:11Z","timestamp":1765601591000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Early upregulation of alpha\u20107 nicotinic acetylcholine receptor in limbic system correlates with gut dysbiosis in mice exposed to binge ethanol"],"prefix":"10.1111","volume":"50","author":[{"given":"Mohammed A. 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