The gut microbiome and host genetics are both associated with major depressive disorder (MDD); however, the molecular mechanisms among the associations are poorly understood, especially in the Asian, Chinese group. Our study applied linear discriminant analysis (LDA) effect size (LEfSe) and genome-wide association analysis in the cohort with both gut sequencing data and genomics data. We reported the different gut microbiota characteristics between MDD and control groups in the Chinese group and further constructed the association between host genetics and the gut microbiome. Actinobacteria and Pseudomonades were found more in the MDD group. We found significant differences in the ACE and Chao indexes of alpha diversity while no discrepancy in beta diversity. We found three associations between host genetics with microbiome features: beta diversity and rs6108 (p = 8.65 × 10–9), Actinobacteria and rs77379751 (p = 8.56 × 10–9), and PWY-5913 and rs1775633082 (p = 4.54 × 10–8). A species of the Romboutsia genus was co-associated with the species of Ruminococcus gnavus in an internetwork through four genes: METTL8, ITGB2, OTULIN, and PROSER3, with a strict threshold (p < 5 × 10–4). Furthermore, our findings suggested that the gut microbiome diversity might affect microRNA expression in the brain and influenced SERPINA5 and other spatially close genes afterward. These findings suggest new linkages between depression and gut microbiome in Asian, Chinese people, which might be mediated by genes and microRNA regulation in space distance.
Neferine (Nef) might possess anti-depressive properties; however, its therapeutic effects are yet to be elucidated. Therefore, in this study, we aimed to explore the anti-depressant property of Nef using a mouse model of chronic stress-induced depression. Fifteen depression-prone mice were randomly selected and divided into three groups, namely, the model, Nef, and fluoxetine (Flu) groups. We observed that in tail suspension and forced swimming tests, the Nef and Flu treatments significantly decreased the immobility time of the depressed mice, and increased their sucrose preference indices. Moreover, both Nef and Flu treatments induced significant increases in the levels of anti-depressant neurotransmitters, including dopamine (DA), serotonin (5-HT), and norepinephrine (NE), and also reduced pathological damage to the hippocampus of the depressed mice. Incidentally, Illumina MiSeq sequencing analysis demonstrated that the relative abundance of Lactobacillus in the intestinal microbiota of depressed mice was restored after Nef/Flu treatment. Moreover, colonic Lactobacillus abundance was positively correlated with the levels of DA, 5-HT, and NE in the hippocampus of the mice. In conclusion, Nef improved monoamine neurotransmitter secretion and modulated the intestinal flora structure, particularly the abundance of Lactobacillus. Hence, it showed considerable anti-depressant potential, and might be a prospective anti-depressant therapeutic agent.
Preeclampsia (PE) confers a significant risk for subsequent diagnosis with autism spectrum disorder (ASD), with the mechanisms underlying this observation being largely unknown. To identify molecular networks affected by both PE and ASD, we conducted a large-scale literature data mining and a gene set enrichment analysis (GSEA), followed by an expression mega-analysis in 13 independently profiled ASD datasets. Sets of genes implicated in ASD and in PE significantly overlap (156 common genes; p = 3.14E −67), with many biological pathways shared (94 pathways; p < 1.00E −21). A set of PE-driven molecular triggers possibly contributing to worsening the risk of subsequent ASD was identified, possibly representing a regulatory shift toward greater vulnerability to the development of ASD. Mega-analysis of expression highlighted RPS4Y1, an inhibitor of STAT3 that is expressed in a sexually dimorphic manner, as a contributor to both PE and ASD, which should be evaluated as a possible contributor to male predominance in ASD. A set of PE-driven molecular triggers may shift the developing brain toward a greater risk of ASD. One of these triggers, chromosome Y encoded gene RPS4Y1, an inhibitor of STAT3 signaling, warrants evaluation as a possible contributor to male predominance in ASD.
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