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Larger study adds to evidence linking leaky gut, immune response, and chronic depression

  [ 8 votes ]   [ Discuss This Article ] • March 17, 2012

Increased IgA and IgM responses against gut commensals in chronic depression: Further evidence for increased bacterial translocation or leaky gut
- Source: Journal of Affective Disorders, Mar 11, 2012

By Michael Maes, et al.

[Note: Commensals are bacteria that may live peacefully on or in the body (e.g., in the gut but not in the blood stream). IgM antibodies are found in blood and lymph fluid; IgA antibodies protect body surfaces exposed to foreign substances, e.g., gut lining, membrane in nose.]

Background: Recently, we discovered that depression is accompanied by increased IgM and IgA responses directed against gram negative gut commensals. [See also their recent report finding this association in chronic fatigue syndrome (ME/CFS) patients.]

The aim of this study was to replicate these findings in a larger study group of depressed patients and to examine the associations between the IgA and IgM responses to gut commensals and staging of depression as well as the fatigue and somatic (F&S) symptoms of depression.

Methods: We measured serum concentrations of IgM and IgA against the LPS [lipopolysaccarides, found in the cell walls] of gram-negative enterobacteria, i.e., Hafnia alvei, Pseudomonas aeruginosa, Morganella morganii, Pseudomonas putida, Citrobacter koseri, and Klebsiella pneumoniae in 112 depressed patients and 28 normal controls.

The severity of fatigue and somatic symptoms was measured using the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale.


• The prevalences and median values of serum IgM and IgA against LPS of these commensals were significantly higher in depressed patients than in controls.

• The IgM levels directed against the LPS of these commensal bacteria were significantly higher in patients with chronic depression than in those without.

• The immune responses directed against LPS were not associated with melancholia or recurrent depression.

• There was a significant correlation between the IgA response directed against LPS and gastro-intestinal symptoms.

Discussion: The results indicate that increased bacterial translocation with immune responses to the LPS of commensal bacteria may play a role in the pathophysiology of depression, particularly chronic depression.

Bacterial translocation may:

a)    Occur secondary to systemic inflammation in depression and intensify and perpetuate the primary inflammatory response once the commensals are translocated; or

b)    Be a primary trigger factor associated with the onset of depression in some vulnerable individuals.

The findings suggest that “translocated” gut commensal bacteria activate immune cells to elicit IgA and IgM responses and that this phenomenon may play a role in the pathophysiology of (chronic) depression by causing progressive amplifications of immune pathways.

Source: Journal of Affective Disorders, Mar 11, 2012. Maes M, Kubera M, Leunis JC, Berk M. Maes Clinics, Tria, Bangkok, Thailand; Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland; Laboratory Ategis, Waver, Belgium; Mental Health Research Institute, Parkville, Australia; Deakin University, School of Medicine, Barwon Health, Geelong, Australia; University of Melbourne, Department of Psychiatry, Parkville, Australia; Orygen Youth Health Research Centre, Parkville, Australia. [Email:]

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