Wong Kingston E, Luft Carolina, Vella Victoria R, Ainsworth-Cruickshank Garrett R J, Wijesundara Kanishka K, Holman Parker J, Bodnar Tamara S, Raineki Charlis
Department of Psychology, Brock University, St. Catharines, Ontario, Canada.
Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Aug 30;141:111454. doi: 10.1016/j.pnpbp.2025.111454. Epub 2025 Jul 18.
Prenatal alcohol exposure (PAE) has been shown to increase vulnerability to anxiety. Alterations in the gut microbiota and its functional products (i.e., short-chain fatty acids, SCFAs) are a potential mechanism underlying anxiety behaviors induced by PAE. Here, we used a rat model of PAE to examine the impact of alcohol consumption during gestation on anxiety-like behaviors, gut microbiota, and SCFA levels in adult male and female offspring. PAE male and female rats exhibited increased anxiety-like behavior on the open field test; moreover, control animals displayed striking sex differences in the light-dark test, but sex differences were attenuated among PAE males and females. Furthermore, using an anxiety index composed of open field and light-dark behaviors, we showed that PAE animals had higher anxiety scores compared to controls. PAE did not affect bacterial diversity and community structure; however, in males, PAE reduced the abundance of the Firmicutes phylum, increased the abundance of the Bacteroidota phylum, and decreased the abundance of the Lachnospiraceae NK4A136 group genus compared to controls. In females, PAE increased abundance of Turicibacter genus compared to controls. PAE did not affect fecal SCFA levels; however, lower levels of butyric and valeric acid were associated with higher anxiety among PAE females. This study identified several bacterial taxa and SCFAs potentially involved in the mechanisms through which PAE induces anxiety-like behaviors. These findings also underscore the importance of considering sex differences when assessing anxiety-like behavior and gut microbiota to identify potential biomarkers for interventions targeting mental health issues in individuals with PAE.
产前酒精暴露（PAE）已被证明会增加焦虑易感性。肠道微生物群及其功能产物（即短链脂肪酸，SCFAs）的改变是PAE诱导焦虑行为的潜在机制。在此，我们使用PAE大鼠模型来研究孕期饮酒对成年雄性和雌性后代焦虑样行为、肠道微生物群和SCFA水平的影响。PAE雄性和雌性大鼠在旷场试验中表现出增加的焦虑样行为；此外，对照动物在明暗试验中表现出显著的性别差异，但PAE雄性和雌性之间的性别差异减弱。此外，使用由旷场和明暗行为组成的焦虑指数，我们发现与对照组相比，PAE动物的焦虑得分更高。PAE不影响细菌多样性和群落结构；然而，在雄性中，与对照组相比，PAE降低了厚壁菌门的丰度，增加了拟杆菌门的丰度，并降低了毛螺菌科NK4A136组属的丰度。在雌性中，与对照组相比，PAE增加了Turicibacter属的丰度。PAE不影响粪便SCFA水平；然而，丁酸和戊酸水平较低与PAE雌性中较高的焦虑相关。本研究确定了几种可能参与PAE诱导焦虑样行为机制的细菌分类群和SCFAs。这些发现还强调了在评估焦虑样行为和肠道微生物群时考虑性别差异的重要性，以便为针对PAE个体心理健康问题的干预措施确定潜在的生物标志物。
