Are back problems influenced by your gut?

By Vijay Kumar MalesuReviewed by Danielle Ellis, B.Sc.Oct 25 2024

Researchers found that patients with degenerative spondylolisthesis had up to three times higher levels of certain gut bacteria compared to those without the condition. 

In a recent study published in The Journal of Orthopaedic Research – Spine, a group of researchers investigated the association between gut microbiome dysbiosis and lumbar degenerative spondylolisthesis (LDS) (forward slipping of a lower spine vertebra caused by degenerative changes) in symptomatic patients.

Background 

Chronic low back pain is a leading global cause of disability, often stemming from multifactorial factors like disc degeneration. LDS results from intervertebral disc and facet joint degeneration, causing vertebral slippage, pain, and potential surgical intervention. Predominantly affecting adults over 50, especially females, LDS is linked to facet joint arthritis, ligamentous laxity, and disc space narrowing.

Emerging evidence indicates that gut microbiome dysbiosis may influence systemic inflammation and spinal health. Understanding the gut-spine axis is crucial, necessitating the need for further research into microbiome contributions to spinal disorders.

About the study

A cross-sectional analysis was conducted using data from the Rush Omics Spine Study Cohort, comprising 51 adults aged 18 to 80 who underwent lumbar spine surgery for herniated discs or symptomatic disc degeneration. Participants were categorized into LDS and non-LDS groups based on imaging from First Lumbar Vertebra (L1) to First Sacral Vertebra (S1) levels. Exclusion criteria included spinal deformities, malignancies, infections, recent antibiotic use, and various comorbidities. Demographic and clinical data, along with pain and disability scores, were collected preoperatively and at multiple postoperative intervals.

Radiographic assessments involved standardized standing lumbosacral radiographs and 1.5 T magnetic resonance imaging (MRI) scans to evaluate spinal parameters and confirm LDS severity using established classification systems. Stool samples were collected, Deoxyribonucleic Acid (DNA) extracted, and the gut microbiome analyzed through high-throughput 16S Ribosomal Ribonucleic Acid (rRNA) gene sequencing.

Bioinformatics processing utilized Quantitative Insights Into Microbial Ecology 2 (QIIME2) for quality control, taxonomy assignment, and diversity analyses. Statistical analyses were performed in R, comparing microbial diversity and composition between LDS and non-LDS groups while adjusting for confounders such as age and body mass index (BMI). 

Study results 

A total of 33 patients were included in the study, with 21 diagnosed with LDS and 12 without. The mean age of the LDS group was 50.3 years (±18.7), compared to 61.9 years (±8.06) in the non-LDS group, though this difference was not statistically significant (p = 0.089).

The gender distribution showed that 25% of the LDS group were female, compared to 52.4% in the non-LDS group and 75% male in LDS versus 47.6% in non-LDS, without significant differences (p = 0.240). The majority of participants were White, comprising 66.7% of the LDS group and 71.4% of the non-LDS group, with no significant racial differences (p = 1).

The mean BMI was similar between groups, 29.1 kg/m² (±5.69) for LDS and 28.3 kg/m² (±5.24) for non-LDS (p = 0.760). Smoking status and alcohol consumption varied slightly but did not reach statistical significance.

Surgical management differed significantly between groups (p = 0.001). In the LDS group, 66.7% underwent combined discectomy (Surgical removal of a herniated disc) and laminectomy (Surgical removal of part of the vertebral bone), and 16.7% received fusion surgery, compared to the non-LDS group where 30.3% had discectomy/laminectomy and 57.6% underwent fusion.

Imaging phenotypes revealed 50 LDS conditions among 21 patients, with retrolisthesis (n = 26) and anterolisthesis (n = 24) being nearly equally prevalent. The L4-L5 and L5-S1 spinal levels were most commonly affected, each accounting for 14 cases. Retrolisthesis was most frequent at L2-L3 and L3-L4 levels. Grade 1 LDS was predominant, observed in 82% of cases, followed by Grade 2 (14%) and Grade 3 (4%).

Patients with LDS exhibited significantly higher disc degeneration scores (16.3 ± 3.5) compared to non-LDS subjects (12.8 ± 3.9, p = 0.018). No significant differences were found in lumbar lordosis (LL), pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), PI-LL mismatch, or the presence of Modic changes between the groups.

Gut microbiome analysis demonstrated significant differences in alpha diversity, with LDS patients showing higher Shannon indices, Evenness Simpson, and Chao1 scores compared to non-LDS individuals. Beta diversity assessments revealed distinct microbial community structures between the groups permutational MANOVA (PERMANOVA) r² = 0.063, p = 0.040), which remained significant after adjusting for age, BMI, and sex. Additionally, the Firmicutes to Bacteroidota ratio was significantly elevated in the LDS group (p = 0.0031).

Differential abundance analysis identified six taxa with significant variations; LDS patients had increased levels of pro-inflammatory bacteria such as Dialister and CAG-352, and decreased levels of anti-inflammatory bacteria including Slackia and Escherichia-Shigella. These microbial differences suggest a potential link between gut dysbiosis and the development of LDS.

Conclusions 

To summarize, this study identified distinct gut microbial communities in surgical patients with LDS compared to those without.

Utilizing 16S rRNA gene sequencing, researchers found that LDS patients had higher alpha diversity and different beta diversity, even after adjusting for age and BMI. The Firmicutes to Bacteroidota ratio was significantly elevated in the LDS group.

At the genus level, Dialister and CAG-352 were more abundant, while Slackia and Escherichia-Shigella were reduced in LDS patients. Additionally, disc degeneration severity was greater in the LDS group.