Maternal microbiome disturbance induces deficits in the offspring's behaviors: a systematic review and meta-analysis.

Recent evidence has suggested that changes in maternal gut microbiota in early life may generate neurobiological consequences associated with psychiatric-related abnormalities. However, the number of studies on humans investigating this problem is limited, and preclinical findings sometimes conflict. Therefore, we run a meta-analysis to examine whether maternal microbiota disturbance (MMD) during neurodevelopment might affect the offspring during adulthood. We found thirteen studies, from a set of 459 records selected by strategy registered on PROSPERO (#289224), to target preclinical studies that evaluated the behavioral outcomes of the rodents generated by dams submitted to perinatal enteric microbiota perturbation. The analysis revealed a significant effect size (SMD = -0.51, 95% CI = -0.79 to -0.22, p < .001, T2 = 0.54, I2 = 79.85%), indicating that MMD might provoke behavioral impairments in the adult offspring. The MMD also induces a significant effect size for the reduction of the sociability behavior (SMD = -0.63, 95% CI = -1.18 to -0.07, p = 0.011, T2 = 0.30, I2 = 76.11%) and obsessive-compulsive-like behavior (SMD = -0.68, 95% CI = -0.01 to -1.36, p = 0.009, T2 = 0.25, I2 = 62.82%) parameters. The effect size was not significant or inconclusive for memory and anxiety-like behavior, or inconclusive for schizophrenia-like and depressive-like behavior. Therefore, experimental perinatal MMD is vertically transmitted to the offspring, negatively impacting behavioral parameters related to psychiatric disorders.

Resveratrol ameliorates the effect of maternal immune activation associated with schizophrenia in adulthood offspring.

Maternal exposure to infectious agents such as arboviruses, bacteria, or other protozoans has been associated with an elevated risk of schizophrenia (SZ). Evidence suggests that immunological processes occurring during infection may disturb the neural progenitor, impacting the central nervous system (CNS) functions. Moreover, growing evidence suggests that resveratrol (RSV) has neuroprotective activity through anti-oxidant and anti-inflammatory mechanisms. Therefore, we investigated if the treatment with RSV during pregnancy would prevent the abnormalities associated with a SZ-like phenotype induced by maternal immune activation (MIA). Pregnant dams stimulated with a subcutaneous (s.c.) injection of polyriboinosinic-polyribocytidylic acid (poly I:C; 50 mg/kg), a viral nucleic acid mimetic or vehicle, on gestational day (GD) 12.5, were treated with RSV (40 mg/kg, s.c.) or saline, from GD 9.5 to GD 14.5. On day 45 after birth, the offspring was evaluated using a three-compartment social interaction test, elevated plus maze, and hyperlocomotion test induced by amphetamine. After the behavioral tests, the relative expression of mRNA to synapsin 1 (Syn1), oligodendrocyte transcription factor 1 (Olig1), and SRY (sex-determining region Y)-box 2 (Sox2) was determined in the hippocampus and cortex. Treatment with RSV restored the social behavior and attenuated the hyperlocomotion of the offspring bred by dams submitted to MIA. RSV prevented the effects of MIA on Syn1 and Olig1 expression in the hippocampus and Syn1 in the cortex. The present study showed that maternal treatment with RSV attenuates some of the negative behavioral impacts caused by MIA, with modulation of synaptic and oligodendrogenesis processes.