Mechanisms and pathophysiology leading to development of small intestinal microbial dysbiosis.

Small intestinal microbial dysbiosis (SIMD) describes clinical syndromes attributed to overabundance of microbes within the small intestine. Usually attributed to bacteria (but also less commonly to archaea and fungi), SIMD arises as a secondary condition, when there is disruption of one or more key physiological mechanisms. We provide a comprehensive review of the current understanding of SIMD pathophysiology. We highlight the key physiological factors including gastric acid, pancreatic enzymes, bile acids, small intestinal dysmotility and obstruction, colonic motility, and intestinal mucosal immunity. We then describe the disease states associated with failure of these mechanisms, providing SIMD prevalence estimates for each. Finally, we address some of the controversies regarding SIMD including testing modalities, significance of intestinal methanogen overgrowth, and the role of SIMD in irritable bowel syndrome.