Chronic Fatigue and Pain

Fibromyalgia.
This often highly debilitating condition is characterized by widespread pain, fatigue, and low energy (1). Not to be underestimated are the also common mental complaints that are classified under the term ‘blurred brain’ (brain fog, fibrofog), as a result of which patients cannot maintain focus and are forgetful, which often has even more impact on patients’ lives. pain and fatigue (2). There is still a lot of uncertainty about the cause of fibromyalgia, but it is often seen as a disturbed function of the central nervous system, with pain signals coming in much more strongly than in healthy people (3). This may sound like something that has little to do with the microbiome, but it should be remembered that the nervous system in the gut is very extensive, and that there is a close link between the brain and gut (4,5). It is also striking that a large to very large proportion of fibromyalgia patients (30-75%) also have IBS complaints (6). In addition, there are indications that there is bacterial disturbance in the small intestine in fibromyalgia patients (4,6) and the extent to which this is correlated to the intensity of the pain complaints (7).

Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS)
These conditions are often thought of as one and the same condition. This condition is related to fibromyalgia, but the focus of the complaint pattern is different. Patients with ME / CFS are often severely fatigued, lack a refreshing sleep, and experience fatigue and malaise after physical exertion (8). But they too, like fibromyalgia patients, often suffer from pain, neurological complaints, and a “blurred brain” (brain fog) (8). Unlike fibromyalgia, ME / CFS often appears to develop after a virus infection, and ME / CFS also involves the immune system (9). Perhaps driven by the fact that ME / CFS patients usually end up with doctors of a different discipline than fibromyalgia patients (internists rather than rheumatologists), unlike fibromyalgia, much research has been done in recent years into the relationship between ME / CFS and the microbiome. There appear to be differences in the composition and diversity of the microbiome between patients and healthy persons (10). In addition, there are indications in the blood of patients of the presence of substances of bacterial origin to which the immune system is known to be able to react violently (10,11) and which is probably related to an increased permeability of the intestinal wall (12). In addition, a study in which 60 ME / CFS patients underwent bacteriotherapy (rectal insertion of a bacterial culture) suggests that adaptation of the microbiome can have a major positive effect; 70% of patients got better (13).

References
1. Clauw DJ. Fibromyalgia: A Clinical Review. JAMA. 2014; 311: 1547.
2. Kravitz HM, Katz RS. Fibrofog and fibromyalgia: a narrative review and implications for clinical practice. Rheumatol Int. 2015; 35: 1115–25.
3. Clauw DJ, D’Arcy Y, Gebke K, Semel D, Pauer L, Jones KD. Normalizing fibromyalgia as a chronic illness. Postgrad Med. 2018; 130: 9–18.
4. Galland L. The Gut Microbiome and the Brain. J Med Food. 2014; 17: 1261–72.
5. Zhu X, Han Y, Du J, Liu R, Jin K, Yi W, Zhu X, Han Y, Du J, Liu R, et al. Microbiota-gut-brain axis and the central nervous system. Oncotarget. 2017; 8: 53829–38.
6. Othman M, Aguero R, Lin HC. Alterations in intestinal microbial flora and human disease. Curr Opin Gastroenterol. 2008; 24:11.
7. Malatji BG, Meyer H, Mason S, Engelke UFH, Wevers RA, van Reenen M, Reinecke CJ. A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls. BMC Neurol [Internet]. 2017 [cited 2018 Feb 3]; 17. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426044/
8. Bested AC, Marshall LM. Review of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians. Rev Environ Health. 2015; 30: 223–49.
9. Mensah FKF, Bansal AS, Ford B, Cambridge G. Chronic fatigue syndrome and the immune system: Where are we now? Neurophysiol Clin Clin Neurophysiol. 2017; 47: 131–8.
10. Giloteaux L, Goodrich JK, Walters WA, Levine SM, Ley RE, Hanson MR. Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis / chronic fatigue syndrome. Microbiome [Internet]. 2016 [cited 2018 Feb 4]; 4. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918027/
11. Maes M, Twisk FNM, Kubera M, Ringel K, Leunis J-C, Geffard M. Increased IgA responses to the LPS of commensal bacteria is associated with inflammation and activation of cell-mediated immunity in chronic fatigue syndrome. J Affect Disord. 2012; 136: 909–17.
12. Morris G, Berk M, Carvalho AF, Caso JR, Sanz Y, Maes M. The Role of Microbiota and Intestinal Permeability in the Pathophysiology of Autoimmune and Neuroimmune Processes with an Emphasis on Inflammatory Bowel Disease Type 1 Diabetes and Chronic Fatigue Syndrome. Curr Pharm Des. 2016; 22: 6058–75.
13. Borody TJ, Nowak A, Finlayson S. The GI microbiome and its role in Chronic Fatigue Syndrome: A summary of bacteriotherapy. J Australas Coll Nutr Environ Med. 2012; 31: 3.