Leaky Gut, Leaky Brain?

Abstract

‘Leaky gut’ syndrome, long-associated with celiac disease, has attracted much attention in recent years and for decades, was widely known in complementary/alternative medicine circles. It is often described as an increase in the permeability of the intestinal mucosa, which could allow bacteria, toxic digestive metabolites, bacterial toxins, and small molecules to ‘leak’ into the bloodstream. Nervous system involvement with celiac disease is know to occur even at subclinical levels. Gluten and gluten sensitivity are considered to trigger this syndrome in individuals genetically predisposed to celiac disease. However, the incidence of celiac disease in the general population is quite low. Nevertheless, increased public interest in gluten sensitivity has contributed to expanded food labels stating ‘gluten-free’ and the proliferation of gluten-free products, which further drives gluten-free lifestyle changes by individuals without frank celiac disease. Moreover, systemic inflammation is associated with celiac disease, depression, and psychiatric comorbidities. This mini-review focuses on the possible neurophysiological basis of leaky gut; leaky brain disease; and the microbiota’s contribution to inflammation, gastrointestinal, and blood-brain barrier integrity, in order to build a case for possible mechanisms that could foster further ‘leaky’ syndromes. We ask whether a gluten-free diet is important for anyone or only those with celiac disease.

Lactobacillus pentosus S-PT84 and Rubus suavissimus leaf extract suppress lipopolysaccharide-induced gut permeability and egg allergen uptake

“…These people may be exposed by risk of LPS. Recently, it has been reported that gut permeability is related to Alzheimer's disease, systemic lupus erythematosus, and allergic asthma (Obrenovich 2018;Costa et al 2016;Mu et al 2015;Farshchi et al 2017). Therefore, reducing intestinal hyper permeability could ameliorate not only food allergy but also other diseases.…”

Sex Differences in Stroke Outcome Are Associated With Constitutive Gut Dysbiosis and Stroke-induced Gut Permeability

“…Through the mucosal system and the interepithelial tight junctions, the GI tract continuously regulates trafficking of molecules between the host and the luminal environment. The gut blood barrier is an important component of gut function as it keeps potentially pathogenic bacteria and intestine-specific proteins from leaking out into circulating blood (Obrenovich, 2018). Emerging evidence suggests that gut permeability may precede many of the inflammatory events associated with disease (Arrieta et al, 2006).…”

The role of innate immunity in Alzheimer's disease

“…267,268 Increased gut permeability allows for bacteria, bacterial toxins, and LPS to enter the bloodstream and has been coined "leaky gut." 269,270 This leakiness is instigated by chronic inflammation and gut dysbiosis, which can contribute to systemic inflammation and the decreased BBB integrity associated with aging and AD. 229,269,271 BBB breakdown can ultimately lead to impaired removal of toxic species from the CNS and entry of pathogenic mediators from the periphery.…”

“…269,270 This leakiness is instigated by chronic inflammation and gut dysbiosis, which can contribute to systemic inflammation and the decreased BBB integrity associated with aging and AD. 229,269,271 BBB breakdown can ultimately lead to impaired removal of toxic species from the CNS and entry of pathogenic mediators from the periphery. 269,271 Interestingly, compared with WT controls, APPPS1 mice have altered bacterial species in the gut, including higher levels of the bacteria B thetaiotaomicron.…”

“…229,269,271 BBB breakdown can ultimately lead to impaired removal of toxic species from the CNS and entry of pathogenic mediators from the periphery. 269,271 Interestingly, compared with WT controls, APPPS1 mice have altered bacterial species in the gut, including higher levels of the bacteria B thetaiotaomicron. 229 In these studies, it was also shown that modulating the gut microbiota landscape with probiotics and exercise treatment can improve cognitive functions in APPPS1 mice.…”