• Valerio Tonelli Enrico, Nam Vo, Barbara Methe, Alison Morris, and Gwendolyn Sowa.
• Ferguson Laboratory for Orthopaedic and Spine Research, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, University of Pittsburgh, 200 Lothrop Street, Room E1612, BST, Pittsburgh, PA, 15261, USA. vat19@pitt.edu.
• Eur Spine J. 2022 Dec 1; 31 (12): 360336153603-3615.

PurposeMultiple diverse factors contribute to musculoskeletal pain, a major cause of physical dysfunction and health-related costs worldwide. Rapidly growing evidence demonstrates that the gut microbiome has overarching influences on human health and the body's homeostasis and resilience to internal and external perturbations. This broad role of the gut microbiome is potentially relevant and connected to musculoskeletal pain, though the literature on the topic is limited. Thus, the literature on the topic of musculoskeletal pain and gut microbiome was explored.MethodsThis narrative review explores the vast array of reported metabolites associated with inflammation and immune-metabolic response, which are known contributors to musculoskeletal pain. Moreover, it covers known modifiable (e.g., diet, lifestyle choices, exposure to prescription drugs, pollutants, and chemicals) and non-modifiable factors (e.g., gut architecture, genetics, age, birth history, and early feeding patterns) that are known to contribute to changes to the gut microbiome. Particular attention is devoted to modifiable factors, as the ultimate goal of researching this topic is to implement gut microbiome health interventions into clinical practice.ResultsOverall, numerous associations exist in the literature that could converge on the gut microbiome's pivotal role in musculoskeletal health. Particularly, a variety of metabolites that are either directly produced or indirectly modulated by the gut microbiome have been highlighted.ConclusionThe review highlights noticeable connections between the gut and musculoskeletal health, thus warranting future research to focus on the gut microbiome's role in musculoskeletal conditions.© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

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