Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
Department of Biological Sciences, Southeastern Louisiana University, Hammond, Louisiana, United States of America.
PLoS One. 2023 Jun 9;18(6):e0287145. doi: 10.1371/journal.pone.0287145. eCollection 2023.
Fenbendazole (FBZ) is a common antiparasitic treatment used in research rodent colonies for biosecurity purposes. The effect of this compound has been studied in C57 mice, but never before in a strain of mice that has co-morbidities, such as the blood pressure high (BPH)/5. The BPH/5 mouse is an inbred genetic model of hypertension. While both male and female BPH/5 have high blood pressure, there is a metabolic sexual dimorphism with females displaying key features of obesity. The obese gut microbiome has been linked to hypertension. Therefore, we hypothesized that fenbendazole treatment will alter the gut microbiome in hypertensive mice in a sex dependent manner. To test the influence of FBZ on the BPH/5 gut microbiota, fecal samples were collected pre- and post-treatment from adult BPH/5 mice (males and non-pregnant females). The mice were treated with fenbendazole impregnated feed for five weeks. Post-treatment feces were collected at the end of the treatment period and DNA was extracted, and the V4 region of 16S rRNA was amplified and sequenced using the Illumina MiSeq system. The purpose was to analyze the fecal microbiome before and after FBZ treatment, the results demonstrate changes with treatment in a sex dependent manner. More specifically, differences in community composition were detected in BPH/5 non-pregnant female and males using Bray-Curtis dissimilarity as a measure of beta-diversity (treatment p = 0.002). The ratio of Firmicutes to Bacteroidetes, which has been identified in cases of obesity, was not altered. Yet, Verrucomicrobia was increased in BPH/5 males and females post-treatment and was significantly different by sex (treatment p = 5.85e-05, sex p = 0.0151, and interaction p = 0.045), while Actinobacteria was decreased in the post-treatment mice (treatment p = 0.00017, sex p = 0.5, interaction p = 0.2). These results are indicative of gut dysbiosis compared to pre-treatment controls. Lactobacillus was decreased with FBZ treatment in BPH/5 females only. In conclusion, fenbendazole does alter the gut microbial communities, most notable in the male rather than female BPH/5 mouse. This provides evidence that caution should be taken when providing any gut altering treatments before or during mouse experiments.
芬苯达唑（FBZ）是一种用于生物安全目的的常见抗寄生虫治疗药物，在研究啮齿动物群体中使用。该化合物的作用已在 C57 小鼠中进行了研究，但从未在具有合并症的小鼠品系中进行过研究，例如高血压/5（BPH/5）。BPH/5 小鼠是高血压的近交遗传模型。虽然雄性和雌性 BPH/5 都有高血压，但存在代谢性别二态性，女性表现出肥胖的关键特征。肥胖的肠道微生物组与高血压有关。因此，我们假设芬苯达唑治疗会以性别依赖的方式改变高血压小鼠的肠道微生物组。为了测试 FBZ 对 BPH/5 肠道微生物群的影响，从成年 BPH/5 小鼠（雄性和非妊娠雌性）中收集治疗前和治疗后的粪便样本。用芬苯达唑浸渍的饲料处理小鼠 5 周。在治疗结束时收集治疗后的粪便，并提取 DNA，使用 Illumina MiSeq 系统扩增和测序 16S rRNA 的 V4 区。目的是分析 FBZ 治疗前后的粪便微生物组，结果表明，以性别依赖的方式发生了治疗引起的变化。更具体地说，使用 Bray-Curtis 不相似性作为β多样性的度量，在 BPH/5 非妊娠雌性和雄性中检测到了群落组成的差异（处理 p = 0.002）。在肥胖病例中已确定的厚壁菌门与拟杆菌门的比例没有改变。然而，治疗后 BPH/5 雄性和雌性的疣微菌门增加，并且性别差异显著（处理 p = 5.85e-05，性别 p = 0.0151，交互作用 p = 0.045），而放线菌门在治疗后减少（处理 p = 0.00017，性别 p = 0.5，交互作用 p = 0.2）。与治疗前对照相比，这些结果表明肠道菌群失调。只有在 BPH/5 雌性中，FBZ 治疗会降低乳杆菌的数量。总之，芬苯达唑确实会改变肠道微生物群落，在 BPH/5 雄性小鼠中比在雌性小鼠中更为明显。这表明在进行小鼠实验之前或期间提供任何改变肠道的治疗时应谨慎。
