Journal
PAIN
Volume 164, Issue 2, Pages E66-E76Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000002694
Keywords
Fibromyalgia; Nociplastic pain; Microbiome; Bile acid; Metabolomics
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Recent research has shown that women with fibromyalgia have alterations in the composition and function of their gut microbiome, including changes in certain bile acid-metabolizing bacteria. This study used sequencing and metabolomic approaches to analyze the gut microbiome and circulating bile acids in women with fibromyalgia and healthy controls. The researchers found significant differences in the abundance of bile acid-metabolizing bacteria and the concentration of secondary bile acids in women with fibromyalgia. Serum bile acid levels were highly correlated with symptom severity, suggesting their involvement in nociplastic pain. These findings provide potential diagnostic and mechanistic insights into fibromyalgia.
Alterations in the composition and function of the gut microbiome in women with fibromyalgia have recently been demonstrated, including changes in the relative abundance of certain bile acid-metabolizing bacteria. Bile acids can affect multiple physiological processes, including visceral pain, but have yet to be explored for association to the fibromyalgia gut microbiome. In this study, 16S rRNA sequencing and targeted metabolomic approaches were used to characterize the gut microbiome and circulating bile acids in a cohort of 42 women with fibromyalgia and 42 healthy controls. Alterations in the relative abundance of several bacterial species known to metabolize bile acids were observed in women with fibromyalgia, accompanied by significant alterations in the serum concentration of secondary bile acids, including a marked depletion of alpha-muricholic acid. Statistical learning algorithms could accurately detect individuals with fibromyalgia using the concentration of these serum bile acids. Serum alpha-muricholic acid was highly correlated with symptom severity, including pain intensity and fatigue. Taken together, these findings suggest serum bile acid alterations are implicated in nociplastic pain. The changes observed in the composition of the gut microbiota and the concentration of circulating secondary bile acids seem congruent with the phenotype of increased nociception and are quantitatively correlated with symptom severity. This is a first demonstration of circulating bile acid alteration in individuals with fibromyalgia, potentially secondary to upstream gut microbiome alterations. If corroborated in independent studies, these observations may allow for the development of molecular diagnostic aids for fibromyalgia as well as mechanistic insights into the syndrome.
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