TY - JOUR T1 - What to do about the leaky gut JF - Gut JO - Gut SP - 424 LP - 435 DO - 10.1136/gutjnl-2021-325428 VL - 71 IS - 2 AU - Michael Camilleri AU - Adrian Vella Y1 - 2022/02/01 UR - http://gut.bmj.com/content/71/2/424.abstract N2 - Key messagesSeveral pathophysiological states have been associated with ‘leaky gut’.Advances in measurement of altered intestinal permeability using serum biomarkers or urinary excretion of orally administered sugar probes should facilitate objective measurements of impaired intestinal permeability.Some dietary factors that damage the intestinal barrier include high fat diet, emulsifiers and alcohol.Several dietary components have been reported to restore intestinal barrier function resulting from perturbations, and these components include prebiotics, probiotics, amino acids, minerals and modifying dietary intake of components that damage the barrier. Pharmacological approaches in development, such as divertin, target MAP kinase, which is an important factor in the leak pathway of permeability.These advances should facilitate claims submitted to regulatory agencies that nutrients and supplements require primary evidence from human studies demonstrating that a dietary component is causally associated with maintaining or restoring normal gut barrier structure.The potential role of ‘leaky gut’ or reduced barrier function with increased intestinal permeability has been considered an important factor in intestinal and extraintestinal diseases. Reversing the impairment of barrier function in diseases associated with mucosal damage may be necessary but may not be sufficient to reverse the disease pathogenesis as in inflammatory bowel disease (IBD) or coeliac disease. In these diseases, the underlying immune dysfunction is likely to be a significant factor in perpetuating the disease. Nevertheless, gastrointestinal and extraintestinal diseases that are not associated with predominant inflammation in the small intestine or colon have drawn attention to the potential role of reduced barrier function in disease pathogenesis. These illnesses range from eosinophilic esophagitis to non-alcoholic fatty liver disease and to diverse neuropsychiatric diseases, as summarised elsewhere.1 There are also diverse systemic consequences associated with gut barrier dysfunction including increased inflammation or oxidative stress and decreased insulin sensitivity affecting tissues or organs such as the liver, fat, skeletal, muscle … ER -