The Microbial Road Trip: Are We Nearing the Golden Era of Orthopaedics?

Commentary Modic changes in the lumbar spine are magnetic resonance imaging (MRI) signal changes in vertebral body end plates that were first described in 1988 by Modic et al.1. These changes are (inconsistently) associated with disabling episodes of lower back pain2. The recognition that the intervertebral disc may host microbiota in both typical and pathological circumstances is relatively recent3. Nian et al. aimed to build on these emerging concepts by analyzing both the microbiota and metabolic profiles of discs obtained during lumbar spinal fusion, and identifying differences between patients with and without preoperative MRI findings indicating the presence of Modic changes. We salute the authors for their well-executed study providing novel insights regarding how the compositions of the microbiome and metabolome are linked to Modic changes by showing that both the microbiota and metabolites were significantly different between the groups with and without such changes. In addition to identifying 26 metabolites that were significantly different between the 2 groups, Nian et al. noted that the unsaturated fatty acid pathway was the main pathway that these metabolites were involved in. Furthermore, they found that Mycobacterium, Clostridium, Blautia, and Bifidobacterium were the genera in the microbiota that differed the most between the groups, and that the abundances of these organisms correlated with the levels of the metabolites in a way that further supported the hypothesis that dysregulation of fatty acid metabolism is involved in the pathogenesis of Modic changes. However, it should be stated that the (future) clinical relevance of the study remains unanswered in this study. Although the mechanistic and pathophysiological insights are clearly described and can be considered valuable and relevant, the translation of the findings of the study into the daily practice of clinicians seeing patients with lower back pain associated with Modic changes warrants further study: How might the identification of specific microbial signatures and metabolite alterations influence clinical decision-making in terms of treatment selection, prognostication, and patient selection? How can we improve clinical outcomes through the findings of this study? How can we put the important finding of the identification of unsaturated fatty acid metabolism as a pivotal pathway that appears to underpin Modic changes into perspective and into practice? Building on such questions regarding clinical relevance, future studies in this domain must aim to bridge the grand gap between bench and bedside. Future studies could, for example, focus on redefining the diagnostic criteria for patients with Modic change-related conditions or work toward developing a therapeutic antimicrobial strategy that is individualized to each patient, based on genomic DNA samples obtained in the diagnostic stage. Alternatively, future studies that could perhaps be as relevant and clinically important might focus on extrapolating or expanding the findings and concepts behind this study to areas beyond the lower back4. The highly interesting finding that dysregulation of fatty acid metabolism contributes to the pathogenesis of Modic changes may serve as a very relevant and compelling example that can potentially be extended to other joints having cartilage-related disorders. Overall, this well-executed study may mark a paradigm shift in our current understanding of Modic changes, shedding light on the landscape of the lumbar cartilaginous end plate’s microbiota and metabolites. By unraveling an unexplored association between the presence of Modic changes and the microbiota and metabolites of the lumbar cartilaginous end plate, the study gives us novel usable information on the pathogenesis of Modic changes and can pave the way for specifically targeted therapeutic interventions. Successful early preventive measures could bring us clinicians better and cheaper options to treat our patients with lower back pain, and potentially also our patients with other (potentially inflammation-related) orthopaedic diseases. The golden orthopaedic area is yet to come but, with a better understanding of Modic changes, we are a step further in the right direction.