Chronic low back pain (CLBP) is a complex condition influenced by biological, 1,2 psychological, 3 and environmental factors, 4 affecting mental health, 5–7 productivity, 8–10 and healthcare costs. 11,12 Systemic inflammation, linked to CLBP and its comorbidities, may be regulated by the gut microbiome (GM). 13–17 This study investigates the relationship between GM, pain severity, and disability in CLBP, hypothesizing GM composition (assessed as individual taxa or overall diversity) correlates with pain and disability.
This secondary analysis included 867 adults with CLBP. Upon enrollment, self-reported pain (Numeric Pain Rating Score), disability scores (Oswestry Disability Index, ODI), and stool samples were collected.
GM’s composition was analyzed using 16S rRNA gene sequencing. We implemented abundance- and distribution-based approaches to analyze GM’s associations with clinical variables. For the distribution-based approach, Shannon and Tail alpha-diversity indices were calculated.
Linear regression models explored the associations of clinical outcomes with taxa’s relative abundance and diversity indices. Individual regression models were run for each taxon and each diversity index against pain and ODI. Multiple regressions with all taxa included in the model were also run. All models were adjusted for age, sex, BMI, education level, income, and relationship status.
The average age and BMI were 59 years and 31Kg/m2. The sample was primarily female (60%), white (77%), and 53% had ≥ College education. Pain had a mean value of 5.4 and ODI of 31.2.
For pain, Bifidobacterium (Partial-R2=.006; p=.031), Ruminococcaceae (Partial-R2=.009; p=.006), Megasphera (Partial-R2=.006; p=.026), Clostridia (Partial-R2=.010; p=.005), and Blautia (Partial-R2=.007; p=.018) were significant in the individually adjusted regression models. Blautia (Partial-R2=.010; p=.007), Ruminococcus (Partial-R2=.005; p=.039), Ruminococcaceae (Partial-R2=.010; p=.006), and Clostridia (Partial-R2=.007; p=.023) were significant in the multiple linear regressions.
For ODI, Faecalibacterium (Partial-R2=.006; p=.027), Anaerostipes (Partial-R2=.010; p=.005), Lachnospira (Partial-R2=.019; p<.001), Ruminococcaceae (Partial-R2=.015; p=.001), Barnesiella (Partial-R2=.005; p=.047), Megasphera (Partial-R2=.012; p=.002), and Clostridia (Partial-R2=.006; p=.027) were significant in the individual regressions. Bacteroides (Partial R2=.005; p=.045), Anaerostipes (Partial R2=.006; p=.039), Ruminococcaceae (Partial R2=.010; p=.005), Barnesiella (Partial R2=.006; p=.034), and Megasphera (Partial R2=.008; p=.017) were significant in the multiple linear regressions.
No alpha diversity indices were significantly associated with pain or ODI.
This study identifies differential associations between gut microbiota and pain/ODI, with Ruminococcaceae linked to both. Dysbiosis involving Ruminococcaceae has been associated with chronic pain, though its role in inflammation is context-dependent. Both increased and decreased levels can cause dysbiosis, indicating unknown balancing mechanisms. Blautia also showed a positive association with pain severity, despite previously being linked to both increased and decreased dysbiosis.18–23
Two pro-inflammatory taxa (Megasphaera, Anaerostipes) were positively associated with pain/ODI. Several anti-inflammatory taxa (Ruminococcus, Clostridia, Faecalibacterium, Lachnospira, Barnesiella) showed negative associations, consistent with their roles in modulating neuroimmunity through short-chain fatty acids. However, Bifidobacterium, often anti-inflammatory, was positively linked to pain and ODI. 24–36
These findings suggest that gut dysbiosis in CLBP individuals involves specific taxa rather than overall diversity. This taxa-driven dysbiosis aligns with our hypothesis, highlighting possible systemic dysregulation mechanisms in pain and ODI. Further research is warranted to explore the clinical relevance of GM for CLBP.