Abstract：
The decline in gut microbial diversity in modern humans is closely associated with the rising prevalence of various diseases. It is imperative to investigate the underlying causes of gut microbial loss and restoring methods. Although the impact of non-perinatal antibiotic use on gut microbiota has been recognized, its intergenerational effects remain unexplored. Our previous research has highlighted soil in the farm environment as a key factor for gut microbiome health by restoring gut microbial diversity and balance. In this study, we investigated the intergenerational consequences of antibiotic exposure and the therapeutic potential of sterile soil. We treated C57BL/6 mice with vancomycin and streptomycin for 2 weeks continuously, followed by a 4-8 week withdrawal period before breeding. The process was repeated across 3 generations. Half of the mice in each generation received an oral sterile soil intervention. We assessed gut microbial diversity, anxiety behavior, microglial reactivity, and gut barrier integrity across generations. Antibiotic exposure led to a decrease in gut microbial diversity over generations, along with aggravated anxiety behavior, microgliosis, and altered intestinal tight junction protein expression. Oral sterile soil intervention restored gut microbial diversity in adult mice across generations, concomitantly rescuing abnormalities in behavior, microgliosis, and intestinal barrier integrity. In conclusion, this study simulated an important process of the progressive loss of gut microbiota diversity in modern humans and demonstrated the potential of sterile soil to reverse this process. This study provides a theoretical and experimental basis for research and interventions targeting multiple modern chronic diseases related to intestinal microorganisms.
摘要：
现代人类肠道微生物多样性的下降与各种疾病患病率的上升密切相关。必须研究肠道微生物流失的根本原因和恢复方法。尽管已经认识到非围产期抗生素使用对肠道微生物群的影响，其代际效应仍未被探索。我们之前的研究强调了农场环境中的土壤是通过恢复肠道微生物多样性和平衡来实现肠道微生物组健康的关键因素。在这项研究中,我们调查了抗生素暴露的代际后果和无菌土壤的治疗潜力。我们用万古霉素和链霉素连续治疗C57BL/6小鼠2周，然后在繁殖前进行4-8周的戒断期。该过程在3代中重复。每一代中有一半的小鼠接受了口服无菌土壤干预。我们评估了肠道微生物多样性，焦虑行为,小胶质细胞反应性，和几代人的肠道屏障完整性。抗生素暴露导致几代人的肠道微生物多样性减少，随着焦虑行为的加剧，小胶质细胞增生,改变肠道紧密连接蛋白的表达。口服无菌土壤干预恢复了成年小鼠的肠道微生物多样性，同时挽救行为异常，小胶质细胞增生,和肠道屏障的完整性。总之,这项研究模拟了现代人类肠道微生物多样性逐渐丧失的一个重要过程，并证明了无菌土壤逆转这一过程的潜力。本研究为针对肠道微生物相关的多种现代慢性病的研究和干预提供了理论和实验依据。
