Normalization of the increased translocation of endotoxin from Gram negative enterobacteria (leaky gut) is accompanied by a remission of chronic fatigue syndrome

MCare4U Outpatient Clinics, Belgium.
Neuro endocrinology letters (Impact Factor: 0.8). 01/2008; 28(6):739-44.
Source: PubMed


There is now evidence that chronic fatigue syndrome (CFS) is accompanied by an increased translocation of endotoxins from gram-negative enterobacteria through the gut wall, as demonstrated by increased prevalences and median values for serum IgM and IgA against the endotoxins of gram-negative enterobacteria. This condition can also be described as increased gut permeability or leaky gut and indicates intestinal mucosal dysfunction (IMD). Here we report a case of a 13 year old girl with CFS who showed very high values for serum IgM against the LPS of some enterobacteria and signs of oxidative and nitrosative stress, activation of the inflammatory response system, and IgG3 subclass deficiency. Upon treatment with specific antioxidants and a "leaky gut diet", which both aim to treat increased gut permeability, and immunoglobins intravenously, the increased translocation of the LPS of gram negative enterobacteria normalized and this normalization was accompanied by a complete remission of the CFS symptoms.

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Available from: Michael Maes, Sep 13, 2015
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    • "These circulating Gram-negative bacteria are a major source of LPS, which can activate brain TLR-4 through multiple pathways, inducing a neuroinflammatory response. This proposed mechanism known as “leaky gut” also takes place in patients with depression or chronic fatigue syndrome and it has been related to the inflammatory pathophysiology of the diseases [16,21]. However, the molecular pathways affected may vary between pathologies: in depression, there are significant associations between bacterial translocation and increased oxidative/nitrosative stress pathways [16], while in chronic fatigue syndrome bacterial translocation is accompanied by increased levels of cytokines [21]. "
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    ABSTRACT: The innate immune response is the first line of defence against invading microorganisms and it is also activated in different neurologic/neurodegenerative pathological scenarios. As a result, the family of the innate immune toll-like receptors (TLRs) and, in particular, the genetic/pharmacological manipulation of the TLR-4 signalling pathway emerges as a potential therapeutic strategy. Growing evidence relates stress exposure with altered immune responses, but the precise role of TLR-4 remains partly unknown. The present study aimed to elucidate whether the elements of the TLR-4 signalling pathway are activated after acute stress exposure in rat brain frontal cortex and its role in the regulation of the stress-induced neuroinflammatory response, by means of its pharmacological modulation with the intravenous administration of the TLR-4 specific inhibitor TAK-242. Considering that TLR-4 responds predominantly to lipopolysaccharide from gram-negative bacteria, we checked whether increased intestinal permeability and a resultant bacterial translocation is a potential regulatory mechanism of stress-induced TLR-4 activation. Acute restraint stress exposure upregulates TLR-4 expression both at the mRNA and protein level. Stress-induced TLR-4 upregulation is prevented by the protocol of antibiotic intestinal decontamination made to reduce indigenous gastrointestinal microflora, suggesting a role for bacterial translocation on TLR-4 signalling pathway activation. TAK-242 pre-stress administration prevents the accumulation of potentially deleterious inflammatory and oxidative/nitrosative mediators in the brain frontal cortex of rats. The use of TAK-242 or other TLR-4 signalling pathway inhibitory compounds could be considered as a potential therapeutic adjuvant strategy to constrain the inflammatory process taking place after stress exposure and in stress-related neuropsychiatric diseases.
    Journal of Neuroinflammation 01/2014; 11(1):8. DOI:10.1186/1742-2094-11-8 · 5.41 Impact Factor
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    • "The leaky gut most likely originates from weakening of the tight junctions of the epithelial barrier by inflammatory processes, e.g. increased production of NFκB and IL-6 (Maes et al 2007a; 2007d). Once LPS enters the bloodstream, a cascade of inflammatory mechanisms is triggered, which results into extended NFκB production; increased levels of COX-2, iNOS, and pro-inflammatory cytokines; O&NS induced damage; and consequently symptoms of IO&NS. "
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    ABSTRACT: There is evidence that disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways and a lowered antioxidant status are important pathophysiological mechanisms underpinning myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Important precipitating and perpetuating factors for ME/CFS are (amongst others) bacterial and viral infections; bacterial translocation due to an increased gut permeability; and psychological stress. Recently, Jason et al (2006) reported that the mean age of patients with myalgic encephalomyelitis/chronic fatigue syndrome dying from heart failure, i.e. 58.7 years, is significantly lower than the age of those dying from heart failure in the general US population, i.e. 83.1 years. These findings implicate that ME/CFS is a risk factor to cardio-vascular disorder. This review demonstrates that disorders in various IO&NS pathways provide explanations for the earlier mortality due to cardiovascular disorders in ME/CFS. These pathways are: a) chronic low grade inflammation with extended production of nuclear factor kappa B and COX-2 and increased levels of tumour necrosis factor alpha; b) increased O&NS with increased peroxide levels, and phospholipid oxidation including oxidative damage to phosphatidylinositol; c) decreased levels of specific antioxidants, i.e. coenzyme Q10, zinc and dehydroepiandrosterone-sulphate; d) bacterial translocation as a result of leaky gut; e) decreased omega-3 polyunsatutared fatty acids (PUFAs), and increased omega-6 PUFA and saturated fatty acid levels; and f) the presence of viral and bacterial infections and psychological stressors. The mechanisms whereby each of these factors may contribute towards cardio-vascular disorder in ME/CFS are discussed. ME/CFS is a multisystemic metabolic-inflammatory disorder. The aberrations in IO&NS pathways may increase the risk for cardiovascular disorders.
    Neuro endocrinology letters 12/2009; 30(6):677-93. · 0.80 Impact Factor
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    • "Recently, it was shown that intestinal barrier dysfunction, with an increased translocation of LPS, correlated with serum IgA and IgM against LPS and the inflammatory pathophysiology of depression and chronic fatigue syndrome [27, 28]. Normalization of increased LPS translocation is accompanied by a remission in clinical symptomatologies. "
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    ABSTRACT: Decades of research went into understanding the role that Th1 autoreactive T-cells play in neuroinflammation. Here we describe another effector population, the IL-17-producing T-helper lineage (Th17), which drives the inflammatory process. Through the recruitment of inflammatory infiltration neutrophils and the activation of matrix metalloproteinases, IL-17, a cytokine secreted by Th17 cells, contributes to blood-brain barrier breakdown and the subsequent attraction of macrophages and monocytes into the nervous system. The entry of cells along with the local production of inflammatory cytokines leads to myelin and axonal damage. This activation of the inflammatory response system is induced by different pathogenic factors, such as gut bacterial endotoxins resulting in progressive neurodegeneration by Th17 cells. Through the understanding of the role of bacterial endotoxins and other pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting IL-17 activity. Targeted therapy can restore the integrity of the intestinal and blood-brain barriers using probiotics, N-acetyl-cysteine, α-lipoic acid, resveratrol and others for their patients with autoimmunities, in particular those with neuroinflammation and neurodegeneration.
    Evidence-based Complementary and Alternative Medicine 08/2009; 2011(1741-427X):984965. DOI:10.1093/ecam/nep063 · 1.88 Impact Factor
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