Gut microbiome associations with chronic musculoskeletal pain in older men

Purpose: Gut microbiota have been previously associated with numerous health outcomes in older adults. We aimed to evaluate whether gut microbiota are associated with chronic musculoskeletal pain (MSKP). Methods: We conducted a cross-sectional study among 537 community-dwelling older men (mean age 84 +/- 4 years) from the MrOS multicenter cohort, who did not receive antibiotics or probiotics within 30 days of the Year 14 clinic visit. Using participant self-report via questionnaire, we defined prevalent MSKP as moderate to severe pain in either knee, hip, lower back, or shoulder locations, present on most days for at least 1 month. Stool samples were collected for 16S amplicon sequencing, and microbiome data were processed using the UPARSE pipeline. We assessed alpha-diversity (within sample taxonomic richness and evenness) using Shannon and Inverse Simpson index. We assessed phylogenic beta-diversity (between sample differences) using weighted and unweighted Unifrac. Finally, we examined associations between specific genera and MSKP using the R package DESeq2, which is based on a negative binomial regression model with adjustment for covariates. The Benjamini-Hochberg method was used to adjust for multiple comparisons. Results: 207 subjects (38%) met the definition of moderate to severe MSKP. Most subjects with MSKP (78%) had pain in ≥2 locations, of which low back pain was the most common (73%), followed by knee pain (59%), hip pain (57%), and shoulder pain (44%). Subjects with MSKP were more likely to be white (p=0.03), and have a higher mean BMI (p=0.002). There were no associations between MSKP and either alpha or beta diversity, although alpha diversity varied by race and BMI (both p-values<0.05). DESeq2 analyses of individual taxa with hierarchical adjustment for age, race, and BMI indicated differential abundances of several bacterial genera associated with MSKP and the number of MSKP locations (Color Table 1). Lachnospiraceae Ruminococcus and Anaerostipes genera were enriched in both prevalent MSKP and a higher number of MSKP locations. Conclusions: Gut bacterial genera Lachnospiraceae Ruminococcus and Anaerostipes are associated with both prevalent MSKP and a higher number of MSKP locations in older community-dwelling men. These genera are mucosa-associated, and capable of producing serotonin and tryptamine from dietary tryptophan. Hence these genera may play a role in gut bacterial translocation, systemic inflammation, and neuromediation.