Background: Fibromyalgia (FM) is a complex and common chronic pain disorder that affects 12 million Europeans, most of them women. It is mainly characterized by the presence of generalized pain and sensitivity, as well as significant joint stiffness, chronic fatigue, dizziness, dry mucous membranes, and an extensive list of psychological and cognitive conditions. Currently, there is no molecular analysis to diagnose FM, being mainly detected through clinical self-questionnaires and discard of similar comorbidities. Oxidative stress and intestinal dysbiosis stand out in the last decade as the most studied imbalances that could underlie FM. In fact, the existence of potential markers related with a pro-inflammatory state and oxidative damage have begun to be analyzed in the serum of patients. At the same time, the composition of the intestinal microbiota through studies carried out on fecal samples of FM patients are notably increasing. However, these studies are designed in small cohorts and, as a consequence, obtain inconclusive results. To solve these previous limitations, this study is included in the framework of a randomized, prospective, low-interventional, double-blind and placebo-controlled clinical trial with more than 200 participants, registered as NCT05921409 ( https://clinicaltrials.gov/study/NCT05921409 ).

Objectives: To design a diagnostic and therapeutic panel of specific biomarkers combining the study of plasma proteome and intestinal microbiota in a large cohort of FM patients.

Methods: A group of 210 FM patients and 40 control women were selected according to ACR (American College of Rheumatology) criteria. Data was collected through health questionnaires, and whole blood and stool samples were taken and analyzed. The composition of the intestinal microbiota was identified by 16S rRNA gene sequencing using Illumina technology and plasma proteome study was performed using nLC-MS/MS proteomics approach.

Results: More than 20 microbial taxa were identified with statistically significant differences ( p <0.05) comparing stool samples from FM patients with healthy volunteers. These bacteria were linked to nutrients absorption, immune response and neurotransmitters signaling, among others. Interestingly, through plasma proteomic analysis it was observed that about 40 circulating proteins in peripheral blood resulted as significantly deregulated ( p <0.05) in patients compared to controls. The vast majority of the proteins were related to coagulation, immune system, inflammation and oxidative metabolism. Plasma and microbiota biomarkers analyzed together with clinical data collected in the SF36 and FIQ.R questionnaires showed interesting correlations that provide a valuable tool for FM screening.

Conclusion: The bacteria and proteins identified in this study provide a reliable starting point for solid biomarker discovery in FM patients. Taken into account that the study was designed with the greatest cohort of FM patients published to date, the results obtained are supported by robust and reliable statistics with the ability to differentiate FM patients from healthy volunteers. As a result, the diagnosis time of FM patients and the monitoring of the disease over time could be substantially improved, as well as the study of new therapeutic therapies that act on the proposed biomarkers.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: None declared.