Microbially produced bile acids are associated with increased IgG autoantibodies and poorer mental wellbeing in fibromyalgia.

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. Gut microbiota can produce or alter bile acids (BAs) and short-chain fatty acids (SCFAs), which have important immune and inflammatory functions. Here, we investigate alterations in BA and SCFA concentrations in FM subjects compared to 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 non-conjugated microbially produced (secondary) BAs compared to HC. Additionally, total BA levels 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 poorer mental well-being. These results revealed increased levels of non-conjugated 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.