Leaky gut in chronic fatigue syndrome: A review

There is now evidence that the pathophysiology of chronic fatigue syndrome (CFS) is related to inflammation and oxidative & nitrosative stress (IO&NS) with a) signs of immune activation and a suppression of ex vivo cellular immune responses; and b) damage to membrane lipids, functional proteins and DNA by O&NS. The above disorders are mediated by intracellular inflammation as indicated by an increased production of nuclear factor kappa Βeta (NFκΒ), cyclo-oxygenase-2 (COX-2) and inducible NO synthase (iNOS). The above inflammatory reactions may by activated by a number of etiological factors, e.g. psychological stress, strenuous exercise, viral and bacterial infections. The purpose of this paper is to review the evidence that an increased translocation of gram negative bacteria is another inflammatory pathway that is involved in CFS. The serum concentrations of IgM and IgA to lipopolysaccharide (LPS) of gram-negative enterobacteria, i.e. Hafnia Alvei; Pseudomonas Aeruginosa, Morganella Morganii, Pseudomonas Putida, Citrobacter Koseri, and Klebsielle Pneumoniae are significantly increased in patients with CFS. This suggests that in CFS there is an increased LPS translocation through a weakened tight junction barrier with subsequent gut-derived inflammation. This condition indicates an increased gut permeability or leaky gut. Treatment for 10-14 months with specific antiinflammatory and -oxidative substances (NAIOSs), such as glutamine, N-acetyl cysteine and zinc, with or without immunoglobins intravenously (IVIg), significantly attenuates the initially increased IgA and IgM responses to LPS, showing that the gut-derived inflammation is attenuated and thus that the weakened tight junction barrier is partly restored. The attenuation of gut-derived inflammation predicts the clinical improvement 10-14 months after intake of NAIOSs. The above findings show that an increased translocation of gram negative bacteria with subsequent inflammation is a new pathway that contributes to the systemic IO&NS responses in CFS.