Review article: Intestinal barrier dysfunction and central nervous system disorders - A controversial association

M. Julio-Pieper, J. A. Bravo, E. Aliaga, M. Gotteland

Research output: Contribution to journalReview articlepeer-review

71 Scopus citations


Background Central nervous system (CNS) development and physiopathology are greatly affected by environmental stimuli. The intestinal barrier restricts the entrance of toxins, pathogens, and antigens while modulating the expression of various neuroactive compounds. The existence of a rich gut-to-brain communication raises the possibility that intestinal barrier alterations may take part in the pathophysiology of CNS disorders.

Aim To review evidence associating intestinal barrier dysfunction with the development of CNS disorders.

Methods Literature search was conducted on PubMed using the following terms: intestinal barrier, intestinal permeability, central nervous system, mental disorders, schizophrenia, autism, stress, anxiety, depression, and neurodegeneration.

Results Clinical and animal model studies of the association between intestinal barrier and schizophrenia, autism spectrum disorders, neurodegenerative diseases or depression were reviewed. The majority of reports concentrated on schizophrenia and autism spectrum disorders. About half of these described increased intestinal permeability/mucosal damage in patients compared with healthy controls, with up to 43% of children with autism spectrum disorders and up to 35% of schizophrenia patients displaying abnormally high urinary excretion of the sugars used as permeability markers. However, another substantial group of studies did not find such differences. In autism spectrum disorders, some reports show that the use of diets such as the gluten-free casein-free diet may contribute to the normalisation of lactulose/mannitol ratio, but to date there is no adequately controlled study showing improvement in behavioural symptoms following these dietary interventions.

Conclusions Evidence of altered intestinal permeability in individuals suffering from CNS disorders is limited and cannot be regarded as proven. Moreover the efficacy of targeting gut barrier in the management of neurological and behavioural aspects of CNS disorders has not yet been established, and needs further investigation.

Original languageEnglish
Pages (from-to)1187-1201
Number of pages15
JournalAlimentary Pharmacology and Therapeutics
Issue number10
StatePublished - 1 Nov 2014


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