Mesenteric Panniculitis and the Gut-Mesentery-Metabolic Axis: A Hypothesis-Generating Narrative Review

Mesenteric panniculitis (MP) is an uncommon inflammatory disorder of mesenteric adipose tissue. Its pathophysiology remains unclear. Gut dysbiosis, intestinal barrier dysfunction, metabolic endotoxemia, glycemic variability (GV), and vascular dysfunction have been implicated in inflammatory and metabolic disorders, but their specific involvement in MP has not been established. This narrative review integrates MP-specific clinical evidence with indirect mechanistic evidence from related metabolic, inflammatory, and experimental settings to examine the possible relationships between these mechanisms and MP and their integration within a proposed gut-mesentery-metabolic axis. The literature was reviewed through structured searches of PubMed, Scopus, and Web of Science for relevant publications from 2018 to 2026, supplemented by earlier foundational studies identified through reference-list screening and targeted searches. Current data suggest that dysbiosis and impaired intestinal barrier function may facilitate microbial-product translocation and lipopolysaccharide-mediated inflammatory signaling, while GV may contribute to oxidative stress, endothelial dysfunction, and pro-inflammatory responses. Mesenteric vascular anatomy and impaired regional perfusion may represent additional factors influencing local tissue susceptibility. Recent randomized controlled trials of microbiome-targeted interventions in metabolic disorders have shown heterogeneous effects on glycemic, inflammatory, and microbiota-related outcomes, indicating a need for further investigation of individualized microbiome-directed strategies. Direct evidence that microbial, metabolic, or vascular mechanisms initiate or sustain MP is currently limited. Accordingly, the proposed gut-mesentery-metabolic axis should be interpreted as a hypothesis-generating framework rather than an established causal model. Prospective MP-specific studies integrating microbiome profiling, validated measures of intestinal barrier function, metabolic phenotyping, GV, vascular assessment, and imaging are required to test the proposed relationships.