Inverted day-night eating during pregnancy may harm mother and fetus brain health by increasing inflammation linked to gut microbiome imbalance in rats
Feeding during the inactive phase in pregnant rats is associated with anxiety-like behaviors and abnormal brain development in fetuses.
Mothers in the inactive-phase feeding group showed anxiety-like behaviors, with fewer entries and less time spent in the central zone of an open field.
Active-phase fasting led to elevated levels of inflammatory cytokines in maternal serum and impaired antioxidant capacity.
Intestinal permeability increased, resulting in , including reduced Akkermansia and increased Dubosiella.
Changes in intestinal circadian gene expression and elevated intestinal inflammatory cytokines were noted.
Lipopolysaccharide () translocated into maternal circulation, activating Toll-like receptor 4 and crossing the placental barrier into the fetal brain, raising inflammatory cytokine levels.
Simplified
BACKGROUND: In both humans and rodents, inappropriate feeding times during pregnancy can cause maternal metabolic abnormalities, increasing the risk of neurodevelopmental disorders in both the mother and offspring. Using a rat model, this study investigates whether feeding only during the inactive phase in rats leads to anxiety-like behaviors and abnormal brain development in fetuses through gut microbiota imbalance.
METHODS: 10-week-old female rats in the inactive-phase feeding group (IF group) were first trained for daytime feeding, ensuring that energy intake was statistically insignificant and different from that of the normal diet feeding group (ND group). They were then paired with male rats, and the previous feeding regimen was continued after pregnancy. Anxiety-like behavior was evaluated using the open-field test. Maternal caecal microbiota was analyzed using 16S rRNA sequencing. Enzyme-linked immunosorbent assay (ELISA) measured serum inflammation factors. RT-PCR was employed to assess mRNA levels of integrity genes and inflammatory cytokines in the maternal hippocampi, intestines, fetal brains, and placentae.
RESULTS: There were no statistically significant differences in energy intake or body weight gain between the IF and ND groups. In the open field test, dams in the IF group exhibited anxiety-like behavior, as indicated by fewer entries into and shorter duration in the central zone. Active-phase fasting elevated maternal serum inflammatory cytokine levels and impaired antioxidant capacity. It also increased intestinal permeability and induced , characterized by a decrease in Akkermansia and an increase in Dubosiella. Changes in the expression of intestinal circadian genes and elevated intestinal inflammatory cytokines were observed. Lipopolysaccharide () translocated into the maternal circulation, activated Toll-like receptor 4 (TLR 4), and passed through the compromised placental barrier into the fetal brain, leading to increased expression of inflammatory cytokines in the fetal brain.
CONCLUSIONS: The misalignment between maternal feeding time and the biological clock during pregnancy disrupts the balance of the gut microbiota and peripheral rhythms. The impaired intestinal and placental barriers allow LPS from the gut to infiltrate the maternal hippocampus and fetal brain, increasing inflammation and impacting both maternal and fetal brain health.
Key numbers
205.40±17.14 pg/ml vs. 319.04±31.35 pg/ml
Increase in TNF-α Levels
Serum TNF-α levels in the IF group vs. ND group.
151.46±15.91 ng/g vs. 239.61±6.45 ng/g
Increase in Levels in Cecum
Cecal levels in the IF group vs. ND group.
48.70±9.29 vs. 12.80±2.00 s
Anxiety-like Behavior Indicator
Time spent in the central zone during the open field test.
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Declarations. Ethics approval and consent to participate: The study of laboratory animals was approved by the Harbin Medical University Institutional Animal Care Committee. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
