Increased IgA and IgM responses against gut commensals in chronic depression: Further evidence for increased bacterial translocation or leaky gut

BACKGROUND: Recently, we discovered that depression is accompanied by increased
IgM and IgA responses directed against gram negative gut commensals. 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 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 F&S symptoms was measured using the Fibromyalgia and Chronic Fatigue 
Syndrome Rating Scale. RESULTS: 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.