Gut Inflammation in Chronic Fatigue Syndrome

Shaheen E Lakhan; Annette Kirchgessner


Nutr Metab. 2010;7(1) 

In This Article

Oxidative Stress

It is well known that CFS is accompanied by increased oxidative stress. People with chronic conditions, such as CFS have lower levels of L-glutathione.[74] Research has shown that L-glutathione levels in cells can be dramatically depleted by excessive oxidative stress. In turn, L-glutathione deficiency has been shown to contribute to oxidative stress and disease, resulting in a vicious cycle.

Oxidative stress arises when there is a marked imbalance between the production of reactive oxygen species (ROS) and their removal by antioxidants. In reaction to mild oxidative stress, tissues often respond by producing more antioxidants; however, severe persistent oxidative stress depletes body antioxidant resources and overtakes its ability to produce more antioxidants, leading to lower antioxidant levels and as well as injury in the tissues.

8-OH-deoxy guanosine (8-OHdG) is a commonly used and highly sensitive marker of total oxidative stress in the body. Upon DNA repair, 8-OHdG is excreted in the urine. Numerous studies have indicated that urinary 8-OHdG is not only a biomarker of generalized cellular oxidative stress, but also a risk factor for many diseases including CFS. Elevated urinary 8-OHdG DNA was detected in patients with CFS. Moreover, the level of urinary 8-OHdG in CFS correlated with the severity of depression and malaise.[75] Thus, increased activation of oxidative and nitrosative (IO and NS) pathways, plays a role in CFS. Moreover, measuring urinary 8-OHdG may be a convenient method for evaluating oxidative DNA damage in patients with CFS and could be a sensitive biomarker helpful for the early diagnosis of patients with CFS.

Maes proposed that IO and NS pathways play a key role in the pathophysiology of CFS.[76] Increased plasma concentrations of pro-inflammatory cytokines, oxidative damage, increased COX-2 production, and increased translocation by gram-negative enterobacteria can generate CFS-like symptoms including fatigue, a flu-like malaise, pain, symptoms of IBS, and neurocognitive disorders. In addition, aberrations in IO and NS pathways are interrelated.

For example, viral and bacterial infections and gut-derived inflammation may induce NF-κB and consequently COX-2, inducible nitric oxide synthase (iNOS) and increased levels of pro-inflammatory cytokines. These inflammatory pathways and persistent or reactivating infections induce ROS and radical nitrogen species (RNS), which in turn may damage membrane fatty acids, proteins, DNA and mitochondria. As a consequence, some cellular immune functions may be suppressed, for example, lowered NK cell activity and ex vivo expression of T cell activation markers, such as CD69. Depletion of antioxidants in patients with CFS, partially due to inflammation, may further impair the protection again ROS and RNS, causing more damage to fatty acids, proteins, DNA and mitochondria.[76]


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