Abstract Diverticulitis, an inflammatory complication of colonic diverticulosis, represents a major public health burden, accounting for substantial morbidity and healthcare expenditures. Although traditionally viewed as a purely mechanical process driven by obstruction of diverticular lumens, recent advances suggest dysregulated host immune responses and gut microbial imbalance in its pathogenesis. This evolving understanding has stimulated interest in immunomodulatory and non-surgical therapeutic strategies to prevent and treat diverticulitis. Inflammatory mediators including C-reactive protein (CRP), interleukin-6, interleukin-10, and tumor necrosis factor-α correlate with disease severity and may persist chronically, suggesting a sustained mucosal immune activation. Pharmacologic approaches targeting this axis have yielded mixed results. Systemic corticosteroids and biologic immunomodulators increase the risk of diverticular complications, whereas mesalamine shows inconsistent benefit limited to symptom relief in chronic disease. Rifaximin, a minimally absorbed antibiotic with local anti-inflammatory and microbiota-modulating properties, may modestly reduce recurrence when combined with a high-fiber diet but remains unsupported by major guidelines. Non-pharmacologic strategies, including fiber-rich and anti-inflammatory diets, appear to mitigate disease risk, possibly through favorable modulation of microbial metabolism and short-chain fatty acid production. Emerging microbiome-directed therapies such as probiotics and fecal microbiota transplantation (FMT) show promise in preliminary trials for reducing inflammation and recurrence, though data remain heterogeneous and underpowered. Future research should clarify mechanistic links between immune regulation, microbial ecology, and mucosal integrity, and define standardized protocols for probiotic and FMT interventions. Ultimately, understanding and manipulating the immune-microbiome axis may transform diverticulitis management, offering non-surgical alternatives to colectomy for recurrent disease.
Williams et al. (Mon,) studied this question.