Low back pain patients with Modic type 1 changes exhibit distinct bacterial and non-bacterial subtypes
I Heggli1,2, T Mengis1,2, C J Laux3
1Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Objectives:
Modic type 1 changes (MC1) are vertebral endplate bone marrow (BM) lesions observed on magnetic resonance images in sub-populations of chronic low back pain (CLBP) patients. The etiopathogenesis remains unknown and treatments that modify the underlying pathomechanisms do not exist. We hypothesized that two biological MC1 subtypes exist: a bacterial and a non-bacterial. This would have important implications for developing treatments targeting the underlying pathomechanisms.
Methods:
Intervertebral disc (IVD) samples adjacent to MC1 (n = 34) and control (n = 11) vertebrae were collected from patients undergoing spinal fusion. Cutibacterium acnes (C.acnes) genome copy numbers (GCNs) were quantified in IVD tissues with 16S qPCR, transcriptomic signatures and cytokine profiles were determined in MC1 and control BM by RNA sequencing and immunoassay. Finally, we assessed if C.acnes GCNs are associated with blood plasma cytokines.
Results:
IVD tissues from control levels had <870 C.acnes GCNs/gram IVD. MC1-adjacent IVDs had either "low" (<870) or "high" (>870) C.acnes GCNs. MC1 patients with "high" C.acnes GCNs had upregulated innate immune cell signatures (neutrophil, macrophage/monocyte) and pro-inflammatory cytokines related to neutrophil and macrophage/monocyte function in the BM, consistent with a host defense against bacterium. MC1 patients with "low" C.acnes GCNs had increased adaptive immune cell signatures (T-and B-cell) in the BM and elevated IL-13 blood plasma levels.
Conclusion:
Our study provides the first evidence for the existence of bacterial (C.acnes "high") and non-bacterial (C.acnes "low") subtypes in MC1 patients with CLBP. This supports the need for different treatment strategies.
Insights
Modic type 1 changes in chronic low back pain may have two subtypes: bacterial, indicated by high Cutibacterium acnes, and non-bacterial, with low C. acnes. This discovery suggests distinct treatment approaches are needed for these chronic low back pain subtypes.
Area of Science:
- Spinal imaging and pathology
- Microbiology of bone marrow lesions
- Immunology of chronic pain
Background:
- Modic type 1 changes (MC1) are bone marrow lesions in chronic low back pain (CLBP) patients with unknown causes.
- Current treatments for MC1 do not address underlying pathomechanisms.
- A hypothesis suggests two biological subtypes of MC1 exist: bacterial and non-bacterial.
Purpose of the Study:
- To investigate the potential existence of bacterial and non-bacterial subtypes within Modic type 1 changes.
- To determine if Cutibacterium acnes (C. acnes) is associated with different immune responses in MC1 lesions.
- To inform the development of targeted treatments for CLBP patients with MC1.
Main Methods:
- Quantification of C. acnes genome copy numbers (GCNs) in intervertebral disc (IVD) tissues adjacent to MC1 and control vertebrae using 16S qPCR.
- Transcriptomic and cytokine profile analysis of bone marrow (BM) in MC1 and control groups via RNA sequencing and immunoassay.
- Assessment of the association between C. acnes GCNs and blood plasma cytokine levels.
Main Results:
- MC1-adjacent IVD tissues exhibited either low (<870) or high (>870) C. acnes GCNs.
- MC1 patients with high C. acnes showed upregulated innate immune signatures and pro-inflammatory cytokines in BM.
- MC1 patients with low C. acnes displayed increased adaptive immune signatures and elevated IL-13 in blood plasma.
Conclusions:
- This study provides the first evidence for distinct bacterial (C. acnes high) and non-bacterial (C. acnes low) subtypes in Modic type 1 changes in CLBP patients.
- The findings support the hypothesis of two MC1 subtypes, each associated with different immune responses.
- Differentiation of MC1 subtypes is crucial for developing targeted and effective treatment strategies for chronic low back pain.
Related Concept Videos
01:17Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
01:30Irritable Bowel Syndrome II: Clinical Features and Diagnostic Evaluation
Irritable Bowel Syndrome (IBS) is classified into subtypes based on the predominant bowel habits as determined by the Bristol Stool Form Scale (BSFS). The subtypes are:
01:28Peptic Ulcer Disease III: Clinical Manifestations and Diagnostic Studies
Few clinical manifestations differentiate gastric ulcers from duodenal ulcers. Distinctions in the location, timing, and pain relief are crucial for healthcare providers in differentiating between gastric and duodenal ulcers during clinical assessments.