Taxonomic changes in the gut microbiota are associated with cartilage damage independent of adiposity, high fat diet, and joint injury

Kelsey H Collins,Kristin L Lenz,Drew J Schwartz,Charles A Harris,Farshid Guilak

doi:10.1038/s41598-021-94125-4

Abstract

Lipodystrophic mice are protected from cartilage damage following joint injury. This protection can be reversed by the implantation of a small adipose tissue graft. The purpose of this study was to evaluate the relationship between the gut microbiota and knee cartilage damage while controlling for adiposity, high fat diet, and joint injury using lipodystrophic (LD) mice. LD and littermate control (WT) mice were fed a high fat diet, chow diet, or were rescued with fat implantation, then challenged with destabilization of the medial meniscus surgery to induce osteoarthritis (OA). 16S rRNA sequencing was conducted on feces. MaAslin2 was used to determine associations between taxonomic relative abundance and OA severity. While serum LPS levels between groups were similar, synovial fluid LPS levels were increased in both limbs of HFD WT mice compared to all groups, except for fat transplanted animals. The Bacteroidetes:Firmicutes ratio of the gut microbiota was significantly reduced in HFD and OA-rescued animals when compared to chow. Nine novel significant associations were found between gut microbiota taxa and OA severity. These findings suggest the presence of causal relationships the gut microbiome and cartilage health, independent of diet or adiposity, providing potential therapeutic targets through manipulation of the microbiome.

Highlights

Lipodystrophic mice are protected from cartilage damage following joint injury
Obesity is associated with several factors that potentially contribute to OA, such as gut microbiota dysbiosis, host responses from adipose tissue, circulating inflammatory mediators, and diet
We evaluated a subset of our previously reported cohort[9] using 16S rRNA sequencing of the fecal microbiota in an attempt to separate factors previously associated with OA and obesity to evaluate relations between the gut microbiota and cartilage damage

Summary

Introduction

Lipodystrophic mice are protected from cartilage damage following joint injury. This protection can be reversed by the implantation of a small adipose tissue graft. Cartilage protection in LD mice can be reversed by the implantation of a small transplant of adipose tissue In this respect, comparing the gut microbiota across these conditions provides the opportunity to assess alterations in the gut microbiome while controlling for adipose tissue host-responses, obesogenic diet, and surgical onset of OA. To add mechanistic insight to the evaluation of relations between the gut microbiota, the reintroduction of cartilage damage, and the absence of adipose tissue, we interrogated circulating and local levels of endotoxin, or lipopolysaccharide (LPS) in these animals[10] This experimental design allows for the identification of gut microbiota changes that are associated with the reversal of cartilage protection and the onset of cartilage damage in this context

Objectives

Methods

Results

Conclusion