Leaky gut: mechanisms, measurement and clinical implications in humans

Abstract

The objectives of this review on ‘leaky gut’ for clinicians are to discuss the components of the intestinal barrier, the diverse measurements of intestinal permeability, their perturbation in non-inflammatory ‘stressed states’ and the impact of treatment with dietary factors. Information on ‘healthy’ or ‘leaky’ gut in the public domain requires confirmation before endorsing dietary exclusions, replacement with non-irritating foods (such as fermented foods) or use of supplements to repair the damage. The intestinal barrier includes surface mucus, epithelial layer and immune defences. Epithelial permeability results from increased paracellular transport, apoptosis or transcellular permeability. Barrier function can be tested in vivo using orally administered probe molecules or in vitro using mucosal biopsies from humans, exposing the colonic mucosa from rats or mice or cell layers to extracts of colonic mucosa or stool from human patients. Assessment of intestinal barrier requires measurements beyond the epithelial layer. ‘Stress’ disorders such as endurance exercise, non-steroidal anti-inflammatory drugs administration, pregnancy and surfactants (such as bile acids and dietary factors such as emulsifiers) increase permeability. Dietary factors can reverse intestinal leakiness and mucosal damage in the ‘stress’ disorders. Whereas inflammatory or ulcerating intestinal diseases result in leaky gut, no such disease can be cured by simply normalising intestinal barrier function. It is still unproven that restoring barrier function can ameliorate clinical manifestations in GI or systemic diseases. Clinicians should be aware of the potential of barrier dysfunction in GI diseases and of the barrier as a target for future therapy.

EPA and DHA attenuate deoxynivalenol‐induced intestinal porcine epithelial cell injury and protect barrier function integrity by inhibiting necroptosis signaling pathway

“…It is also important as the first barrier against food contaminants and exogenous or endogenous antigens . However, many factors such as stress, infection, and toxins, can lead to gut damage and barrier dysfunction, which can escalate to intestinal diseases such as inflammatory bowel diseases and necrotizing enterocolitis . Deoxynivalenol (DON) is a mycotoxin that commonly contaminates food or feed .…”

“…[1][2][3] However, many factors such as stress, infection, and toxins, can lead to gut damage and barrier dysfunction, which can escalate to intestinal diseases such as inflammatory bowel diseases and necrotizing enterocolitis. 3 Deoxynivalenol (DON) is a mycotoxin that commonly contaminates food or feed. 4,5 Ingestion of DON-contaminated food or feed leads to altered intestinal structure, 6 compromised intestinal epithelial barrier function, [7][8][9] and lower nutrient absorption, 10 which can lead to severe bowel disease.…”

Gut permeability is affected by sex and increased in children with irritable bowel syndrome but not in functional abdominal pain

“…Lactulose/mannitol urine collection time recommendations have ranged from 2‐24 hours . Thus, we analyzed the sugars in both the 0‐ to 3‐hour and 0‐ to 24‐hour collections.…”

Risk factors associated with intestinal permeability in an adult population: A systematic review

“…Although the concept of IP was first mentioned in the literature during the 1960s and further explored in relation to disease during the 1970s it was not until the 2000s that the mechanism of action for IP development was discovered, providing further clarification into the role IP plays in health and disease . While IP may be considered an emerging health condition that clinicians should be aware of, the consequence of impaired barrier function remains underexamined …”

“…7 While IP may be considered an emerging health condition that clinicians should be aware of, the consequence of impaired barrier function remains underexamined. 8 The loss of intestinal integrity occurs when the transmembrane proteins connecting the cells of the small intestine disassemble in response to a cascade of events involving the protein zonulin. 1 As a result of altered IP, particular aspects of disease such as clinical symptoms, severity and activity have been found to be exacerbated in the presence of IP.…”