Intestinal microbiota are essential for healthy gastrointestinal function and also broadly influence brain function and behavior, in part, through changes in immune function. Gastrointestinal disorders are highly comorbid with psychiatric disorders, although biological mechanisms linking these disorders are poorly understood. The present study utilized rats bred for distinct emotional behavior phenotypes to examine relationships between emotionality, the microbiome, and immune markers. Prior work showed that Low Novelty Responder (LR) rats exhibit high levels of anxiety- and depression-related behaviors as well as myriad neurobiological differences compared to High Novelty Responders (HRs). Here, we hypothesized that the divergent HR/LR phenotypes are accompanied by changes in fecal microbiome composition. We used next-generation sequencing to assess the HR/LR microbiomes and then treated adult HR/LR males with an antibiotic cocktail to test whether it altered behavior. Given known connections between the microbiome and immune system, we also analyzed circulating cytokines and metabolic factors to determine relationships between peripheral immune markers, gut microbiome components, and behavioral measures. There were no baseline HR/LR microbiome differences, and antibiotic treatment disrupted the microbiome in both HR and LR rats. Antibiotic treatment exacerbated aspects of HR/LR behavior, increasing LRs’ already high levels of anxiety-like behavior while reducing passive stress coping in both strains. Our results highlight the importance of an individual’s phenotype to their response to antibiotics, contributing to the understanding of the complex interplay between gut microbes, immune function, and an individual’s emotional phenotype.

肠道微生物群对于健康的胃肠功能至关重要，并且还通过免疫功能的变化广泛影响大脑功能和行为。胃肠道疾病与精神疾病高度共存，尽管人们对这些疾病之间的生物学机制知之甚少。本研究利用针对不同情绪行为表型培育的大鼠来检查情绪、微生物组和免疫标记物之间的关系。先前的研究表明，与高新奇反应（HR）大鼠相比，低新奇反应（LR）大鼠表现出高水平的焦虑和抑郁相关行为，以及无数的神经生物学差异。在这里，我们假设不同的 HR/LR 表型伴随着粪便微生物组组成的变化。我们使用下一代测序来评估 HR/LR 微生物组，然后用抗生素混合物治疗成年 HR/LR 男性，以测试其是否改变行为。鉴于微生物组和免疫系统之间已知的联系，我们还分析了循环细胞因子和代谢因素，以确定外周免疫标记物、肠道微生物组成分和行为测量之间的关系。基线 HR/LR 微生物组不存在差异，抗生素治疗破坏了 HR 和 LR 大鼠的微生物组。抗生素治疗加剧了 HR/LR 行为的各个方面，增加了 LR 本来就很高水平的焦虑样行为，同时减少了两种菌株的被动应激应对能力。我们的结果强调了个体表型对其抗生素反应的重要性，有助于理解肠道微生物、免疫功能和个体情绪表型之间复杂的相互作用。