### Key messages
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 …