Abelmoschus manihot (L.) leaf flavonoids (AMLF) restore cyclophosphamide-induced immunosuppression in mice via gut microbiota and serum metabolomics modulation.

Abstract

Immune homeostasis serves as the foundation for disease prevention and the cornerstone for ensuring human health. The effects of Abelmoschus manihot (L.) leaf flavonoids (AMLF) on restoring immune function were investigated in a cyclophosphamide (CTX)-induced immunosuppressed mouse model. The underlying repair mechanisms were explored by an integrative analysis of intestinal microbiomics and serum metabolomics. The results demonstrated that AMLF markedly elevated the spleen and thymus indices, promoted the proliferation of splenic lymphocytes in the presence of concanavalin A (ConA) or lipopolysaccharide (LPS) and CD4+ and CD8+ T lymphocyte subsets, and concomitantly enhanced the serum levels of key immunomodulatory cytokines, including interleukin-1β (IL-1β), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α), and the antibody immunoglobulin G (IgG). In addition, AMLF treatment effectively mitigated CTX-induced histopathological injuries to immune organs and the colon. AMLF were also found to protect the liver by regulating antioxidant enzyme activities. Furthermore, AMLF markedly improved the intestinal microbial community structure, promoted the enrichment of beneficial bacteria (Lactobacillaceae and Prevotellaceae), inhibited pathogenic bacteria (Muribaculaceae and Desulfovibrionaceae), and increased the content of short-chain fatty acids (SCFAs). Serum metabolomic analysis showed that AMLF upregulated the levels of leukotrienes, S-(PGA1)-glutathione and prostaglandin E2. Correlation analysis identified g_Alistipes, g_norank_f_Muribaculaceae, and g_Kurthia as potential microbiota strongly associated with the restoration of immune and metabolic homeostasis after AMLF treatment. These findings support the dual potential of AMLF in functional foods and as immunomodulatory adjuvants.