Role of Vitamin D Status and Alterations in Gut Microbiota Metabolism in Fibromyalgia-Associated Chronic Inflammatory Pain

<b>Background/Objectives</b>: Several studies suggest gut microbiota metabolites as important immuno-modulators in inflammatory pain. We aimed to investigate the relationship between vitamin D status and gut dysbiosis markers in fibromyalgia (FM)-associated chronic inflammation. <b>Methods</b>: Blood samples were collected from sixty-eight female FM patients (49.9 ± 12.35 years). Pain intensity was assessed by FIQ-R. The serum levels of the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-17, IFN-γ, as well as those of vitamin D (25(OH)D3) and the kynurenine/tryptophan ratio (Kyn/Trp) were determined by ELISA and HPLC, respectively. The plasma levels of the SCFAs acetate, butyrate, and propionate were detected by GC-MS. <b>Results</b>: A mean FIQ-R score indicated that the patients could be classified as having moderate FM. The mean levels of all cytokines, but IL-6 and IL-1β, were higher than the normal reference values. The highest concentrations of cytokines were observed in patients showing the highest FIQ-R scores and the lowest 25(OH)D3 levels. Deficient levels of acetate were found paralleled by an increase in Kyn/Trp. The highest acetate concentrations were detected in patients with the lowest FIQ-R scores and 25(OH)D3 levels. Significantly negative correlations were found between 25(OH)D3 concentrations and FIQ-R scores (<i>p</i> = 0.007) as well as IL-17 levels (<i>p</i> = 0.002) and between acetate and TNF-α (<i>p</i> = 0.040) as well as FIQ-R scores (<i>p</i> = 0.028), while significantly positive correlations were observed between Kyn/Trp and IL-17 (<i>p</i> = 0.027) as well as IFN-γ (<i>p</i> = 0.003). <b>Conclusions</b>: Our preliminary data suggest that the vitamin D status along with altered gut microbiota metabolism plays a major role in FM-related inflammatory pain. Replication of these findings in a larger cohort is required to provide additional insights.