Macrophage polarization reprogramming by resveratrol: A novel mechanism for protecting the intestinal mucosal barrier in sepsis (Review)

Sepsis is characterized by a life‑threatening organ dysfunction caused by a dysregulated host response to infection. A key clinical feature of sepsis is disruption of the intestinal mucosal barrier, which not only increases intestinal permeability but also facilitates the translocation of bacteria and toxins, thereby exacerbating systemic inflammatory responses. M1/M2 macrophage polarization imbalance as an important contributor to sepsis‑induced intestinal mucosal injury. M1 macrophages promote tissue damage primarily through proinflammatory mechanisms during sepsis, whereas M2 macrophages contribute to tissue repair and inflammation resolution through anti‑inflammatory responses. However, dysregulated M1/M2 macrophage polarization during sepsis may aggravate intestinal inflammation and impair barrier function. Resveratrol, a natural plant compound, has demonstrated anti‑inflammatory, antioxidant and immunomodulatory properties and has been reported to alleviate various pathological conditions, including sepsis‑induced intestinal mucosal barrier dysfunction. Resveratrol may mitigate the inflammatory environment in sepsis and promote intestinal mucosal barrier repair through modulation of macrophage polarization. However, most current evidence is derived from experimental studies and further investigation is required to clarify its clinical applicability. The present review aimed to comprehensively examine the mechanisms underlying sepsis‑induced intestinal mucosal barrier damage and its association with M1/M2 macrophage polarization and to explore the potential role of resveratrol in regulating macrophage polarization and alleviating sepsis‑associated intestinal injury. By synthesizing current research, the present review identified critical gaps in knowledge and discusses future directions for understanding the role of resveratrol‑mediated immunomodulation in sepsis‑associated intestinal barrier dysfunction.