Microbially Produced Bile Acids are Associated with High Levels of IgG Autoantibodies and Worse Mental Well-being in Fibromyalgia Subjects

Fibromyalgia (FM) is a disease primarily associated with chronic widespread pain, but other common symptoms are anxiety and depression. We previously proposed that autoimmunity contributes to FM based on findings of increased immunoglobulin G binding to satellite glial cells (anti-SGC IgG) in FM subjects compared to healthy controls (HC). Emerging research suggests that an altered gut microbiota composition is connected to psychological symptoms in FM rather than pain. Gut microbiota can produce or alter bile acids (BAs) and short-chain fatty acids (SCFAs), which have immune and inflammatory functions. Here, we investigate alterations in BA and SCFA concentrations in FM subjects compared to healthy controls (HC) and potential associations with FM symptoms and anti-SGC IgG levels.

Bile acids and SCFAs were quantified using liquid chromatography coupled with high-resolution mass spectrometry and anti-SGC IgG levels were assessed with immunocytochemistry. The correlations between FM symptoms, anti-SGC IgG levels, and serum concentrations of 24 BAs and 11 SCFAs in 35 FM subjects and 32 matched HC were examined.

Fibromyalgia subjects had significantly higher levels of microbially produced BAs than HC. Strikingly, 11 out of 24 BAs were significantly elevated in FM subjects with high, compared to those with low, anti-SGC IgG levels. Concentrations of specific BAs were associated with increased disease severity and worse mental well-being.

These results revealed increased levels of secondary BAs in FM subjects compared to HC. The strong association between BAs, anti-SGC IgG levels, and mental well-being may help elucidate the importance of BAs in the psychological symptoms of FM.

Significance statement

Fibromyalgia (FM) is a chronic pain syndrome that significantly impacts an individual’s quality of life. In addition to persistent pain, people with FM often experience depression, anxiety, and irritable bowel syndrome. Previously, we identified autoantibodies that bind to satellite glial cells in the dorsal root ganglia associated with more severe FM symptoms. Our current results demonstrate a novel association between these autoantibodies in FM and bile acids (BAs). Bile acids are essential for lipid metabolism but also act as signaling molecules. We show that patients with elevated levels of autoantibodies also exhibit increased levels of BAs. Furthermore, the BAs strongly correlate with worse FM symptom severity, particularly affecting mental well-being. Our study suggests that lowering BA levels could alleviate the psychological symptoms associated with FM.