Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery.

Background: There is growing evidence of the significance of gastrointestinal complaints in the impairment of the intestinal mucosal barrier function and inflammation in fibromyalgia (FM) and in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, data on intestinal permeability and gut barrier dysfunction in FM and ME/CFS are still limited with conflicting results. This study aimed to assess circulating biomarkers potentially related to intestinal barrier dysfunction and bacterial translocation and their association with self-reported symptoms in these conditions. Methods: A pilot multicenter, cross-sectional cohort study with consecutive enrolment of 22 patients with FM, 30 with ME/CFS and 26 matched healthy controls. Plasma levels of anti-beta-lactoglobulin antibodies (IgG anti-ß-LGB), zonulin-1 (ZO-1), lipopolysaccharides (LPS), soluble CD14 (sCD14) and interleukin-1-beta (IL-1ß) were assayed using ELISA. Demographic and clinical characteristics of the participants were recorded using validated self-reported outcome measures. The diagnostic accuracy of each biomarker was assessed using the receiver operating characteristic (ROC) curve analysis. Results: FM patients had significantly higher levels of anti-ß-LGB, ZO-1, LPS, and sCD14 than healthy controls (all P < 0.0001). In ME/CFS patients, levels of anti-ß-LGB, ZO-1, LPS, and sCD14 were significantly higher than controls, but lower than in FM (all P < 0.01), while there was no significant difference in IL-1ß level. In the FM and ME/CFS cohorts, both anti-ß-LGB and ZO-1 correlated significantly with LPS and sCD14 (P < 0.001 for both). In the FM group, both anti-ß-LGB and ZO-1 were correlated significantly with physical and mental health components on the SF-36 scale (P < 0.05); whereas IL-1ß negatively correlated with the COMPASS-31 score (P < 0.05). In the ME/CFS cohort, ZO-1 was positively correlated with the COMPASS-31 score (P < 0.05). The ROC curve analysis indicated a strong ability of anti-ß-LGB, ZO-1, LPS and sCD14 to predictively distinguish between FM and ME/CFS from healthy controls (P < 0.0001). Conclusion: Biomarkers of intestinal barrier function and inflammation were associated with autonomic dysfunction assessed by COMPASS-31 scores in FM and ME/CFS respectively. Anti-ß-LGB antibodies, ZO-1, LPS, and sCD14 may be putative predictors of intestinal barrier dysfunction in these cohorts. Further studies are needed to assess whether these findings are causal and can therefore be applied in clinical practice.

Overtraining Syndrome: one more piece of the Central Sensitivity Syndrome puzzle / Síndrome de Sobreentrenamiento: una pieza más del puzle del Síndrome de Sensibilidad Central / Síndrome do supertreinamento: mais uma peça do enigma da Síndrome de Sensibilização Central

The initial focus of overtraining syndrome was physical overexertion with inadequate rest, causing severe chronic fatigue and decreased performance. The pathophysiological knowledge has subsequently evolved, and although the exact mechanisms of overtraining syndrome are unknown, several hypotheses arise. The most prominent of these are: the existence of an immunoneuroendocrine imbalance and dysfunction of the central nervous system and of the neuroendocrine axis. On the other hand, central sensitivity syndrome encompasses nosological entities that share the pathophysiological mechanisms that cause them, that is, an immunoneuroendocrine and mitochondrial dysfunction as well as an oxidative stress imbalance. The most common entities within central sensitivity syndrome are fibromyalgia, tension headache and/or migraine, chronic fatigue syndrome, irritable bowel syndrome, multiple chemical syndrome, electrosensitivity syndrome, irritable bladder syndrome, and restless leg syndrome, among others. The pathophysiological and clinical analogy between overtraining syndrome and central sensitivity syndrome raises the possibility of including overtraining syndrome within central sensitivity syndrome, since a stressful stimulus such as chronic overtraining coupled with unbalanced compensatory systems can generate, at a given time, immunoneuroendocrine sensitization and therefore central sensitivity syndrome

El enfoque inicial del síndrome de sobreentrenamiento ha sido el sobreesfuerzo físico con un descanso no adecuado, que provocaba fatiga crónica severa y disminución en el rendimiento. Posteriormente ha ido evolucionando el conocimiento fisiopatológico, y aunque se desconocen los mecanismos fisiopatológicos exactos del síndrome de sobreentrenamiento, se plantean diversas hipótesis. Las más destacadas son: la existencia de un desbalance inmunoneuroendocrino y disfunción del sistema nervioso central y el eje neuroendocrino. Por su parte el síndrome de sensibilidad central engloba entidades nosológicas que tienen en común las razones fisiopatológicas que las ocasionan, esto es, una disfunción inmunoneuroendocrina, mitocondrial y un desbalance del estrés oxidativo. Las entidades más comunes dentro del síndrome de sensibilidad central suelen ser la fibromialgia, la cefalea tensional y/o migraña, el síndrome de fatiga crónica, el síndrome de intestino irritable, el síndrome químico múltiple, el síndrome de electrosensibilidad, el síndrome de la vejiga irritable, el síndrome de piernas inquietas, entre otros. La analogía fisiopatológica y clínica entre el síndrome de sobreentrenamiento y el síndrome de sensibilidad central, plantea la posibilidad de englobar al síndrome de sobreentrenamiento dentro del síndrome de sensibilidad central, ya que ante la presencia de un estímulo estresante como lo es el sobreentrenamiento crónico, unido a sistemas compensadores desequilibrados, puede generar en un momento determinado una sensibilización

O foco inicial da síndrome do supertreinamento foi o excesso de esforço físico com descanso inadequado, causando fadiga crônica grave e diminuição do desempenho. Posteriormente o conhecimento fisiopatológico evoluiu e, embora os mecanismos exatos da síndrome do supertreinamento sejam desconhecidos, surgem várias hipóteses. Os mais proeminentes são: a existência de um desequilíbrio imunoneuroendócrino e disfunção do sistema nervoso central e do eixo neuroendócrino. Por outro lado, a síndrome da sensibilização central engloba entidades nosológicas que compartilham os mecanismos fisiopatológicos que as causam, ou seja, uma disfunção imunoneuroendócrina e mitocondrial, bem como um desequilíbrio de estresse oxidativo. As entidades mais comuns dentro da síndrome da sensibilização central são fibromialgia, cefaleia e/ou enxaqueca, síndrome de fadiga crônica, síndrome do intestino irritável, síndrome química múltipla, síndrome de eletrosensibilidade, síndrome da bexiga irritável e síndrome das pernas inquietas, entre outros. A analogia fisiopatológica e clínica entre síndrome do supertreinamento e síndrome da sensibilização central levanta a possibilidade de incluir a síndrome do supertreinamento dentro da síndrome da sensibilização central, uma vez que um estímulo estressante, como o supertreinamento crônico, juntamente com sistemas compensatórios desequilibrados, pode gerar, em determinado momento, sensibilização imunoneuroendócrina e, portanto, síndrome da sensibilização central