Evidence for a shift towards a proinflammatory/pronociceptive signature of gut dysbiosis in patients with axial chronic low back pain: A preliminary cross-sectional analysis

Nonspecific or axial-chronic low back pain is not attributed to specific pathology yet accounts for 80%- 90% of all chronic low back pain cases and is a major cause of disability affecting one in four adults with treatment costs and lost wages totaling $100-200 billion. Despite its prevalence, there is a knowledge gap around the underlying mechanisms driving susceptibility to this type of chronic pain. Gut microbial colonization plays a role in shaping host physiology directly through interactions with host tissues and indirectly through the production of metabolites, but the role of the microbiome in the etiology of axial-low back pain is unclear. Using a cross-sectional design, in this preliminary study, patients with axial-chronic low back pain and healthy controls completed the NIH minimal dataset for chronic low back pain from the PROMIS short form followed by collection of rectal swabs and 16S rRNA sequencing and determination of microbiome composition differences between controls and patients. Our findings suggest a distinct pattern of altered colonization in axial-chronic low back pain, characterized by a specific pattern of increased formate- and succinate- producing bacterial abundance along with reduced abundance of key taxa associated with butyrate, propionate, and acetate production. A review of the literature available on metabolite production from differentially abundant bacteria suggests a proinflammatory/ pronociceptive shift in microbial colonization. These preliminary findings identify a gut dysbiosis pattern that may contribute to chronic low back pain through pro-inflammatory and pronociceptive mechanisms; however, larger, longitudinal, and metabolically profiled studies are needed to confirm causality. PERSPECTIVE: Chronic low back pain is associated with gut dysbiosis characterized by reduced abundance of butyrate and/or propionate producing bacteria combined with increased succinate- and formate-producing bacterial colonization. These data suggest a proinflammatory/pronociceptive microbial signature that may contribute to development and/or maintenance of chronic low back pain.