Combrink Leigh, Spaan Johannie M, Perret Alexis, Maehara Thomas, Hyun Britney, Parker Dana, Johns Jennifer L, Blouin Michael S, Magnusson Kathy, Steinauer Michelle L
School of Natural Resources and the Environment, University of Arizona, Tucson, Arizona, United States of America.
Department of Biomedical Sciences, Western University of Health Sciences, Lebanon, Oregon, United States of America.
PLoS Negl Trop Dis. 2025 Jun 12;19(6):e0013088. doi: 10.1371/journal.pntd.0013088. eCollection 2025 Jun.
Parasitic helminths infect over 2 billion people, primarily those living in poverty. Helminth infections typically establish in early childhood and persist through critical periods of growth and development, leading to cognitive deficits and/or behavioral changes. These deficits could result from the helminths themselves or due to dysbiosis of the gut microbiota and its influence on the gut-brain axis. Using two cohorts of 3-week-old female mice, we measured levels of anxiety, fear, compulsion, spatial learning, and spatial memory, between schistosome-infected and sham-exposed mice. Additionally, we compared their fecal microbiomes using 16S rRNA gene sequencing at two time points during the chronic stage of infection. Schistosome-infected mice showed higher levels of anxiety in the open field test, reduced spatial learning in the Morris water maze task, and enhanced memory retention in the novel object task. All mice performed equally on the marble bury task. Each cohort started with unique microbiota which showed marked changes in the beta diversity of their microbiota after exposure. In both cohorts, at 7- weeks post exposure, infected mice had more Alistipes sp. and Bacteroides thetaiotaomicron and less Turicibacter sp. and Ligilactobacillus sp. than uninfected mice. At 10 weeks, infected mice had more Alistipes sp. and fewer Muribaculaceae sp. Interestingly, taxon shifts in infected mice were those typically associated with protective effects on liver disease and IL-10 gut conditions, suggesting a possible protective role of the shifted microbiome. Our analyses did not indicate associations between behavioral measures and microbiome composition; however, this could be due to the strong impact of infection on the microbiome composition. Findings here uncover behavioral and cognitive impacts of schistosome infection and shed light on the complex interplay between schistosome infection, behavioral changes, and host microbiome composition, which could ultimately support future global health efforts.
寄生性蠕虫感染着超过20亿人，主要是生活在贫困中的人群。蠕虫感染通常在儿童早期就已确立，并在生长和发育的关键时期持续存在，导致认知缺陷和/或行为改变。这些缺陷可能是由蠕虫本身引起的，也可能是由于肠道微生物群失调及其对肠-脑轴的影响所致。我们使用两组3周龄的雌性小鼠，测量了感染血吸虫的小鼠和假暴露小鼠之间的焦虑、恐惧、强迫、空间学习和空间记忆水平。此外，我们在感染的慢性阶段的两个时间点，使用16S rRNA基因测序比较了它们的粪便微生物群。感染血吸虫的小鼠在旷场试验中表现出更高的焦虑水平，在莫里斯水迷宫任务中空间学习能力下降，而在新物体任务中记忆保持能力增强。所有小鼠在大理石掩埋任务中的表现相同。每组小鼠开始时都有独特的微生物群，暴露后其微生物群的β多样性发生了显著变化。在两组中，暴露后7周，感染小鼠比未感染小鼠有更多的阿里斯杆菌属和嗜热栖热放线菌，而Turicibacter菌属和 Ligilactobacillus菌属较少。在10周时，感染小鼠有更多的阿里斯杆菌属和更少的毛螺菌科。有趣的是，感染小鼠中的分类群变化通常与对肝脏疾病和IL-10肠道状况的保护作用相关，这表明微生物群的变化可能具有保护作用。我们的分析没有表明行为指标与微生物群组成之间存在关联；然而，这可能是由于感染对微生物群组成的强烈影响。此处的研究结果揭示了血吸虫感染对行为和认知的影响，并阐明了血吸虫感染、行为变化和宿主微生物群组成之间的复杂相互作用，这最终可能为未来的全球卫生工作提供支持。
