The gut-brain barrier in major depression: (leaky gut) plays a role in the inflammatory pathophysiology of depression

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Neuro Endocrinol Lett. 2008 Feb 24;29(1):117-124 [Epub ahead of print]

The gut-brain barrier in major depression: Intestinal mucosal

dysfunction with an increased translocation of LPS from gram negative

enterobacteria (leaky gut) plays a role in the inflammatory

pathophysiology of depression.

Maes M, Kubera M, Leunis JC.

M-Care4U Outpatient Clinics, and the Clinical Research Center for

Mental Health, Belgium. crc.mh@....

There is now evidence that major depression (MDD) is accompanied by

an activation of the inflammatory response system (IRS) and that

pro-inflammatory cytokines and lipopolysacharide (LPS) may induce

depressive symptoms. The aim of the present study was to examine whether

an increased gastrointestinal permeability with an increased

translocation of LPS from gram negative bacteria may play a role in the

pathophysiology of MDD. Toward this end, the present study examines the

serum concentrations of IgM and IgA against LPS of the gram-negative

enterobacteria, Hafnia Alvei, Pseudomonas Aeruginosa, ella

ii, Pseudomonas Putida, Citrobacter Koseri, and Klebsielle

Pneumoniae in MDD patients and normal controls. We found that the

prevalences and median values for serum IgM and IgA against LPS of

enterobacteria are significantly greater in patients with MDD than in

normal volunteers. These differences are significant to the extent that

a significant diagnostic performance is obtained, i.e. the area under

the ROC curve is 90.1%. The symptom profiles of increased IgM and IgA

levels are fatigue, autonomic and gastro-intestinal symptoms and a

subjective feeling of infection. The results show that intestinal

mucosal dysfunction characterized by an increased translocation of

gram-negative bacteria (leaky gut) plays a role in the inflammatory

pathophysiology of depression. It is suggested that the increased LPS

translocation may mount an immune response and thus IRS activation in

some patients with MDD and may induce specific " sickness behaviour "

symptoms. It is suggested that patients with MDD should be checked for

leaky gut by means of the IgM and IgA panel used in the present study

and accordingly should be treated for leaky gut.

PMID: 18283240 [PubMed - as supplied by publisher]

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