Florida State University, Biomedical Sciences Department, Tallahassee, FL, United States.
University of Florida, Psychology Department, Gainesville, FL, United States.
Alcohol. 2024 Nov;120:169-178. doi: 10.1016/j.alcohol.2024.01.006. Epub 2024 Jan 28.
Ceftriaxone is an antibiotic that increases central nervous system (CNS) protein expression of the glutamate transporters GLT-1 and xCT and ameliorates pathological behaviors in rodent models of neurological disease and substance use disorder. However, little ceftriaxone passes through the blood-brain barrier, the CNS binding partner of ceftriaxone is unknown, and ceftriaxone does not consistently upregulate GLT-1 and xCT in cell culture. Ceftriaxone alters the gut microbiome composition in rodents and humans, and the microbiome-gut-brain axis regulates drug-seeking. Thus, here we test the hypothesis that ceftriaxone reduces alcohol intake while ameliorating alcohol-induced disruption of the gut microbiome composition. Male and female Sprague-Dawley rats received intermittent access to alcohol (IAA) while controls received access to only water. Following 17 IAA sessions, ceftriaxone/vehicle treatment was given for 5 days. Analysis of the gut microbiome composition was assessed by 16S rRNA gene amplicon sequencing conducted on fecal pellets collected prior to and after alcohol consumption and following ceftriaxone treatment. Male rats displayed escalated alcohol intake and preference over the course of the 17 sessions; however, total alcohol intake did not differ between the sexes. Ceftriaxone reduced alcohol intake and preference in male and female rats. While alcohol affected a diverse set of amplicon sequencing variants (ASV), ceftriaxone markedly reduced the diversity of microbial communities reflected by a blooming of the Enterococcaceae family. The remaining effects of ceftriaxone, however, encompassed families both affected and unaffected by prior alcohol drinking and highlight the Ruminococcaceae and Muribaculaceae families as bidirectionally modulated by alcohol and ceftriaxone. Altogether, our study confirms that ceftriaxone reduces alcohol intake in rats and partially reverses alcohol-induced dysbiosis.
头孢曲松是一种抗生素，可增加谷氨酸转运体 GLT-1 和 xCT 在中枢神经系统 (CNS) 中的蛋白表达，并改善神经疾病和物质使用障碍啮齿动物模型中的病理行为。然而，很少有头孢曲松能穿过血脑屏障，头孢曲松在中枢神经系统中的结合伴侣尚不清楚，并且头孢曲松在细胞培养中并不一致地上调 GLT-1 和 xCT。头孢曲松改变了啮齿动物和人类的肠道微生物组组成，而微生物组-肠道-大脑轴调节觅药行为。因此，在这里我们测试了这样一个假设，即头孢曲松可以减少酒精摄入量，同时改善酒精引起的肠道微生物组组成的破坏。雄性和雌性 Sprague-Dawley 大鼠接受间歇性酒精摄入（IAA），而对照组只接受水。在 17 次 IAA 后，给予头孢曲松/载体治疗 5 天。通过对粪便样本中的 16S rRNA 基因扩增子测序分析，评估肠道微生物组组成，这些粪便样本在酒精摄入前后以及头孢曲松治疗后收集。雄性大鼠在 17 次的过程中表现出酒精摄入量增加和偏好；然而，雄性和雌性大鼠之间的总酒精摄入量没有差异。头孢曲松减少了雄性和雌性大鼠的酒精摄入量和偏好。虽然酒精影响了一整套扩增子测序变体（ASV），但头孢曲松显著降低了微生物群落的多样性，这反映在肠球菌科家族的繁荣。然而，头孢曲松的其余影响包括受先前饮酒影响和不受影响的家族，并突出了厚壁菌门和毛螺菌科家族被酒精和头孢曲松双向调节。总之，我们的研究证实，头孢曲松可减少大鼠的酒精摄入量，并部分逆转酒精引起的失调。
