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Key messages
Several 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.
Introduction
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 …
Footnotes
Correction notice This article has been corrected since it published Online First. An acknowledgement has been added to table 3.
Contributors MC: conceptualisation, writing and revising the manuscript. AV: coauthorship of main body of manuscript, including metabolic and nutritional perspectives.
Funding MC receives funding for studies on intestinal permeability from National Institutes of Health (grant #R01-DK115950) and from the Institute for the Advancement of Food and Nutrition Sciences (IAFNS) (through an ILSI North America Carbohydrate Committee grant). IAFNS is a non-profit science organisation that pools funding from industry and advances science through the in-kind and financial contributions from private and public sector members.
Competing interests MC has submitted a patent application on “Methods and materials for assessing intestinal permeability; Publication number: 20190145953” with colleagues at Mayo Clinic. AV has no conflicts of interest.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.