And improving LPS levels and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and inhibiting the TLR4/MyD88 pathway with herbal formula Zuogui Jiangtang Jieyu (ZJJ) by downregulating Gram-negative bacteria abundance alleviated diabetes-associated MDD (95). The gene discussed is TLR4; the disease is major depressive disorder.