Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 6 (4)

Leaky Gut, Leaky Brain?


Leaky Gut, Leaky Brain?

Mark E M Obrenovich. Microorganisms.


'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.

Keywords: blood barriers; celiac disease; gluten; gluten-free; inflammation; leaky brain; leaky gut; metabolic interactome; microbiome; microbiota; microbiota-gut-brain axis.

Conflict of interest statement

The authors declare no conflicts of interest.

Similar articles

See all similar articles

Cited by 5 articles


    1. Obrenovich M., Sankar Chittoor Mana T., Rai H., Shola D., Christopher S., McCloskey B., Levison B.S. Recent findings within the microbiota-gut-brain-endocrine metabolic interactome. Pathol. Lab. Med. Int. 2017;9:21–30. doi: 10.2147/PLMI.S121487. - DOI
    1. Obrenovich M., Rai H., Chittoor Mana T.S., Shola D., McCloskey B., Sass C., Levison B. Dietary co-metabolism within the microbiota-gut-brain-endocrine metabolic interactome. BAO Microbiol. 2007;2:022.
    1. Obrenovich M.E., Donskey C.J., Scheifer I.T., Bongiovanni R., Li L., Jaskiw G.E. Quantification of phenolic acid metabolites in humans by LC-MS: A structural and targeted metabolomics approach. Bioanalysis. 2018;10:1591–1608. doi: 10.4155/bio-2018-0140. - DOI - PubMed
    1. Braniste V., Al-Asmakh M., Kowal C., Kowal C., Anuar F., Abbaspour A., Tóth M., Korecka1 A., Bakocevic N., Ng L.G. The gut microbiota influences blood-brain barrier permeability in mice. Sci. Transl. Med. 2014;6:263ra158. doi: 10.1126/scitranslmed.3009759. - DOI - PMC - PubMed
    1. Siniscalco D., Schultz S., Brigida A.L., Antonucci N. Inflammation and neuro-immune dysregulations in autism spectrum disorders. Pharmaceuticals. 2018;11:56 doi: 10.3390/ph11020056. - DOI - PMC - PubMed