A further examination of growth factors, T helper 1 polarization, and the gut microbiome in major depression: Associations with reoccurrence of illness, cognitive functions, suicidal behaviors, and quality of life

Growth factors, T helper (Th)1 polarization, and the microbiome are involved in the pathophysiology of major depression (MDD). It remains unclear whether the combination of these three pathways could enhance the accuracy of predicting the features of MDD, including recurrence of illness (ROI), suicidal behaviors and the phenome. We measured serum stem cell factor (SCF), stem cell growth factor (SCGF), stromal cell-derived factor-1 (SDF-1), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), macrophage-colony stimulating factor (M-CSF) and vascular endothelial growth factor (VEGF), the ratio of serum Th1/Th2 cytokines (zTh1-zTh2), and the abundances of gut microbiome taxa by analyzing stool samples using 16S rDNA sequencing from 32 MDD patients and 37 healthy controls. The results show that serum SCF is significantly lower and VEGF increased in MDD. Adverse childhood experiences (ACE) and ROI are significantly associated with lowered SCF and increasing VEGF. Lifetime and current suicidal behaviors are strongly predicted (63.5%) by an increased VEGF/SCF ratio, Th1 polarization, a gut microbiome enterotype indicating gut dysbiosis, and lowered abundance of Dorea and Faecalobacterium. Around 80.5% of the variance in the phenome's severity is explained by ROI, ACEs, and lowered Parabacteroides distasonis and Clostridium IV abundances. A large part of the variance in health-related quality of life (54.1%) is explained by the VEGF/SCF ratio, Th1 polarization, ACE, and male sex. In conclusion, key features of MDD are largely predicted by the cumulative effects of ACE, Th1 polarization, aberrations in growth factors and the gut microbiome with increased pathobionts but lowered beneficial symbionts.