The Gut Microbiota in Osteoarthritis

Where Do We Stand and What Can We Do?

Xiaoxia Hao; Xingru Shang; Jiawei Liu; Ruimin Chi; Jiaming Zhang; Tao Xu

Disclosures

Arthritis Res Ther. 2021;23(42) 

In This Article

Abstract and Introduction

Abstract

Osteoarthritis (OA) is one of the most frequent musculoskeletal diseases characterized by degeneration of articular cartilage, subchondral bone remodeling, and synovial membrane inflammation, which is a leading cause of global disability, morbidity, and decreased quality of life. Interpreting the potential mechanisms of OA pathogenesis is essential for developing novel prevention and disease-modifying therapeutic interventions. Gut microbiota is responsible for a series of metabolic, immunological, and structural and neurological functions, potentially elucidating the heterogeneity of OA phenotypes and individual features. In this narrative review, we summarized research evidence supporting the hypothesis of a "gut-joint axis" and the interaction between gut microbiota and the OA-relevant factors, including age, gender, genetics, metabolism, central nervous system, and joint injury, elucidating the underlying mechanisms of this intricate interaction. In the context, we also speculated the promising manipulation of gut microbiota in OA management, such as exercise and fecal microbiota transplantation (FMT), highlighting the clinical values of gut microbiota. Additionally, future research directions, such as more convincing studies by the interventions of gut microbiota, the gene regulation of host contributing to or attributed to the specific phenotypes of gut microbiota related to OA, and the relevance of distinct cell subgroups to gut microbiota, are expected. Moreover, gut microbiota is also the potential biomarker related to inflammation and gut dysbiosis that is able to predict OA progression and monitor the efficacy of therapeutic intervention.

Introduction

Osteoarthritis (OA) is one of the most frequent musculoskeletal diseases characterized by degeneration of articular cartilage, subchondral bone remodeling, synovial membrane inflammation causing pain, morning stiffness, swelling, limited range of joint motion, and poor physical function, which is a leading cause of global disability, morbidity, and decreased quality of life.[1] With aging and increasing obesity population, the prevalence of osteoarthritis is rising, particularly since the mid-twentieth century, impacting 303 million individuals globally in 2017 and resulting in unsustainable clinical, humanistic, and economic burdens composed of medical care costs, lost wages, and depressed economic productivity.[2–4]

OA is now recognized as a collection of multiple subgroups, each with specific pathophysiological and clinical features dependent on the risk factors involved, such as metabolic syndrome-associated osteoarthritis, post-traumatic osteoarthritis, and aging-associated osteoarthritis.[5–7] These risk factors independently or intricately contribute to a complex interaction between mechanical, biochemical, and cellular factors, leading to the pathogenesis of OA. Identifying phenotypes of patients may help to detect the disease at its early stage and could be used to guide clinical decision making and allow more effective and specific therapeutic interventions targeted toward individuals. As a result, it is meaningful to identify an underlying but important individual feature, gut microbiota, to better understand the heterogeneity of OA phenotypes.

Gut microbiota, defined as a collection of gut microbe populations, is responsible for a series of metabolic, immunological, structural, and neurological functions, such as maintenance of metabolic homeostasis, development and maturation of immune system, resistance to infections, and production of neurotransmitters.[8] The most representative bacterial phyla in gut microenvironment are Firmicutes and Bacteroidetes, followed by Verrucomicrobia, Actinobacteria, Fusobacteria, Proteobacteria, and Cyanobacteria.[9] Due to its incredible involvements, microbial dysbiosis, defined as an adverse alteration in the diversity, structure, or function of gut microbiota, contributes to diverse pathological states and diseases. Gut microbiota is involved in the initiation and progression of inflammation-driven diseases, and microbial dysbiosis has been emerged as a hidden risk factor inducing the production of proinflammatory cytokines and bacterial metabolites, which may boost the pathophysiological mechanisms of OA.[10] OA risk factors, such as aging, diet, and obesity, are shown to perturbate gut microbiota, while limited evidence supports the involvement of gut microbiota upon the mechanisms of these risk factors.

In this review, we summarized the evidence supporting the hypothesis of "gut-joint" axis and the interactions between gut microbiota and OA-relevant factors and assessed the potentials of microbiota-targeted therapies in OA management (Table 1, Figure 1). Based on the current understanding of the crosstalk between gut microbiota and these factors, gut microbiota could be considered as an indispensable element that provides a unifying mechanism to explain the involvement of these individual-level risk factors in OA.

Figure 1.

Relationship between the gut microbiota and osteoarthritis development. OA-relevant factors are involved in OA either directly, or via the modulation of gut microbiota. Several disease-modifying therapeutic approaches can relieve OA symptoms directly, or via altering the composition of gut microbiota to influence OA progression indirectly. OA, osteoarthritis

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