Maternal sleep deprivation (MSD) is a global public health problem that affects the physical and mental development of pregnant women and their newborns. The latest research suggests that sleep deprivation (SD) disrupts the gut microbiota, leading to neuroinflammation and psychological disturbances. However, it is unclear whether MSD affects the establishment of gut microbiota and neuroinflammation in the newborns. In the present study, MSD was performed on pregnant Sprague-Dawley rats in the third trimester of pregnancy (gestational days 15-21), after which intestinal contents and brain tissues were collected from offspring at different postnatal days (P1, P7, P14, and P56). Based on microbial profiling, microbial diversity and richness increased in pregnant rats subjected to MSD, as reflected by the significant increase in the phylum Firmicutes. In addition, microbial dysbiosis marked by abundant Firmicutes bacteria was observed in the MSD offspring. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) showed that the expression levels of proinflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly higher in the MSD offspring at adulthood (P56) than in the control group. Through Spearman correlation analysis, IL-1β and TNF-α were also shown to be positively correlated with Ruminococcus_1 and Ruminococcaceae_UCG-005 at P56, which may determine the microbiota-host interactions in MSD-related neuroinflammation. Collectively, these results indicate that MSD changes maternal gut microbiota and affects the establishment of neonatal gut microbiota, leading to neuroinflammation in MSD offspring. Therefore, understanding the role of gut microbiota during physiological development may provide potential interventions for cognitive dysfunction in MSD-impacted offspring.
孕期睡眠剥夺(Maternal sleep deprivation, MSD)已成为影响孕产妇身心健康及新生儿早期发育的全球公共卫生问题。最新的研究进展表明，睡眠剥夺(Sleep deprivation, SD)会破坏肠道微生物群，导致宿主神经炎症和精神异常。然而，尚不清楚MSD是否会影响新生儿肠道菌群的建立和神经炎症。该研究对妊娠晚期(妊娠15～21天)的Sprague-Dawley大鼠进行MSD处理，然后在出生后不同时间点(P1、P7、P14、P56)收集子代的肠道内容物和脑组织。通过菌群测序发现，受MSD影响的孕鼠粪便微生物多样性和丰富度增加，主要表现为厚壁菌门显著增加；同时我们在MSD子代中也观察到以厚壁菌门类细菌增多为标志的肠道菌群失调。进一步的qRT-PCR和ELISA检测发现，MSD成年后代脑内促炎细胞因子IL-1β和TNF-α的表达显著高于对照组(P56)。Spearman相关性分析显示，IL-1β和TNF-α与Ruminococcus_1和Ruminococcaceae_UCG-005这两类厚壁菌门的丰度呈正相关，从而提示肠道菌群与宿主神经发育密切相关。综上所述，MSD改变了母体肠道菌群，并影响了子代早期肠道菌群的建立，最后导致MSD后代出现特定菌群相关的神经炎症。因此，揭示肠道菌群在个体生理发育过程中的作用，将可能为治疗MSD后代的认知功能障碍提供潜在的干预措施。.
Keywords: Cognitive function; Firmicutes; Gut microbiota; Gut-brain axis; Maternal sleep deprivation; Neuroinflammation.