Department of Urology, the First Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, China.
Institute of Urology, Anhui Medical University, Hefei, Anhui, China.
Prostate. 2020 Jun;80(9):663-673. doi: 10.1002/pros.23978. Epub 2020 Apr 7.
Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP).
Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria.
EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and β-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation.
Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition.
大约 78%的慢性前列腺炎/慢性骨盆疼痛综合征（CP/CPPS）患者存在抑郁症状，但病理机制尚不清楚。越来越多的证据表明，肠道微生物群的异常可能在抑郁症中发挥重要作用。因此，我们旨在通过实验性自身免疫性前列腺炎（EAP）小鼠模型来研究肠道微生物群是否通过引起 CP/CPPS 相关的抑郁。
雄性非肥胖型糖尿病（NOD）小鼠通过前列腺抗原和佐剂的皮下注射进行两次免疫。行为测试包括旷场测试、糖水偏好测试、强迫游泳测试和悬尾测试，以确认 EAP 诱导的抑郁样症状。然后，收集粪便样本，进行 16S 核糖体 RNA 基因测序，以检测对照组和 EAP 组之间肠道微生物群组成的差异。此外，将来自对照组和 EAP 组的粪便细菌移植到抗生素诱导的假无菌小鼠中，以研究对宿主行为和肠道细菌组成的影响。
EAP 成功建立，并在小鼠中表现出抑郁样行为。粪便样本的 16S rRNA 分析表明，与对照组相比，EAP 小鼠的肠道微生物群组成异常。在粪便微生物群移植研究中，与未处理的假无菌小鼠相比，抗生素处理的假无菌小鼠表现出抑郁状态。与对照组相比，EAP 小鼠的粪便细菌移植而非对照组的粪便细菌移植，显著加剧了宿主的抑郁样行为。此外，来自对照组和 EAP 组的粪便细菌移植诱导了α多样性和β多样性指数的明显改变。在所有情况下，通过粪便细菌移植，有 24 种细菌在六个进化水平上发生了显著变化。
EAP 诱导后肠道微生物群组成的异常可能导致小鼠抑郁的发生。针对肠道微生物群的治疗策略可能为缓解这种情况提供一种替代治疗方法。
