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Purpose: Multiple 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. Methods: This 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. Results: Overall, 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. Conclusion: The 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. [ABSTRACT FROM AUTHOR]

Answer to the Letter to the Editor of K. Minami, et al. concerning "An unexpected connection: A narrative review of the associations between gut microbiome and musculoskeletal pain" by Tonelli et al. (Eur Spine J; 2022: doi:10.1007/s00586-022-07429-y) The authors appreciate the interest of Dr. Minami et al. in our manuscript and this important topic. Indeed, a recent review has focused on the role of the gut microbiome specific to osteoarthritis pain, which we agree should also be of great interest to investigators entering this field. [Extracted from the article]