The gut microbiome-joint connection: implications in osteoarthritis

Abstract

Purpose of review: Osteoarthritis is a debilitating disease leading to joint degeneration, inflammation, pain, and disability. Despite efforts to develop a disease modifying treatment, the only accepted and available clinical approaches involve palliation. Although many factors contribute to the development of osteoarthritis, the gut microbiome has recently emerged as an important pathogenic factor in osteoarthritis initiation and progression. This review examines the literature to date regarding the link between the gut microbiome and osteoarthritis.

Recent findings: Studies showing correlations between serum levels of bacterial metabolites and joint degeneration were the first links connecting a dysbiosis of the gut microbiome with osteoarthritis. Further investigations have demonstrated that microbial community shifts induced by antibiotics, a germ-free environment or high-fat are important underlying factors in joint homeostasis and osteoarthritis. It follows that strategies to manipulate the microbiome have demonstrated efficacy in mitigating joint degeneration in osteoarthritis. Moreover, we have observed that dietary supplementation with nutraceuticals that are joint protective may exert their influence via shifts in the gut microbiome.

Summary: Although role of the microbiome in osteoarthritis is an area of intense study, no clear mechanism of action has been determined. Increased understanding of how the two factors interact may provide mechanistic insight into osteoarthritis and lead to disease modifying treatments.

Box 1

no caption available

FIGURE 1

Glucosamine and undenatured type II collagen ameliorate posttraumatic osteoarthritis compared with vehicle control. Sham or DMM surgery was initiated on the knee joint 2 weeks after either glucosamine or undenatured type II collagen were introduced in the diet. Representative Safranin O/Fast Green stains collected from mice fed vehicle control (a) glucosamine (b) or undenatured type II collagen (c) are presented (Yellow dotted line = tidemark, Black dotted line box = region of interested viewed at higher magnification, F = femur, M = meniscus, T = tibia, Scale bar at 100× = 100 μm, Scale bar at 200× = 50 μm). Sections like those in (a–c) were used for histomorphometry. Tibia cartilage area, tibia uncalcified cartilage area, and SafO+ chondrocytes were quantified for mice fed glucosamine (d) and undenatured type II collagen (e) compared with vehicle control. Dashed black lines indicate measurement on sham knee joints. Data shown represent mean (n ≥ 5) ± SD; statistical significance was determined using Student's t test ^∗P < 0.5, ^∗∗P < 0.01. DMM, destabilization of the medial meniscus.

FIGURE 2

Supplementation with glucosamine or undenatured type II collagen impacts the gut microbiome. (a) Phylum level relative abundances change when either glucosamine or undenatured type II collagen are included in the diet for 12 weeks following injury compared with a vehicle control. Data shown are average relative abundances of phyla in each experimental group (n = 3). (b) Relative abundance of operational taxonomic unit in the gut microbiome determined by fecal sampling is changed by supplementation with either glucosamine or undenatured type II collagen. Data shown are average relative abundances of operational taxonomic unit in each experimental group (n = 3).

FIGURE 3

Individual operational taxonomic unit are significantly changed by supplementation with glucosamine or undenatured type II collage. (a) Supplementation with glucosamine for 14 weeks caused significant changes in abundance of three operational taxonomic unit compared with vehicle control. (b) Supplementation with undenatured type II collagen for 14 weeks caused significant changes in 5 operational taxonomic unit. Data shown represent mean % abundance (n ≥ 5) ± SD. Significance was determined using Student's t test. ^∗P < 0.05; ^∗∗P < 0.01; ^∗∗∗P < 0.001.