Dietary Derived Propionate Regulates Pathogenic Fibroblast Function and Ameliorates Experimental Arthritis and Inflammatory Tissue Priming.

Jasna Friščić,Mario M Zaiss,Lisa Möller,Kerstin Dürholz,Cecilia Engdahl,Georg Schett,Markus H Hoffmann,Xi Chen

doi:10.3390/nu13051643

Abstract

Short-chain fatty acids are gut-bacteria-derived metabolites that execute important regulatory functions on adaptive immune responses, yet their influence on inflammation driven by innate immunity remains understudied. Here, we show that propionate treatment in drinking water or upon local application into the joint reduced experimental arthritis and lowered inflammatory tissue priming mediated by synovial fibroblasts. On a cellular level, incubation of synovial fibroblasts with propionate or a physiological mixture of short-chain fatty acids interfered with production of inflammatory mediators and migration and induced immune-regulatory fibroblast senescence. Our study suggests that propionate mediates its alleviating effect on arthritis by direct abrogation of local arthritogenic fibroblast function.

Highlights

The gut harbors trillions of bacteria that are constantly interacting with the host, representing a fundamental component underlying health and disease
To assess if propionate is functional when administered locally, we used antigen-induced arthritis (AIA), a T-celldependent model of arthritis that relies on systemic immunization with methylated bovine serum albumin preceding local initiation of inflammation by intra-articular knee injection of mBSA [23]
Propionic Acid (PA)-treated cells were significantly impaired in their ability to transfer tissue priming to naïve paws (Figure 1h), suggesting that PA directly impairs SF function related to arthritis and inflammatory tissue priming

Summary

Introduction

The gut harbors trillions of bacteria that are constantly interacting with the host, representing a fundamental component underlying health and disease. Microbes often communicate with the host through microbiota-derived metabolites. One major class of metabolites are short-chain fatty acids (SCFAs). The SCFAs acetate, propionate (propionic acid, PA), and butyrate are the main metabolites produced in the gut by bacterial fermentation of dietary fiber and resistant starch. Besides local effects in the gut, SCFAs have several immunomodulatory capacities and exert effects on remote target organs. PA was shown to shift Th1 and Th17 cells to a T regulatory cell (Treg) phenotype and thereby promote amelioration of multiple sclerosis [1] and allergic lung inflammation [2,3]. There is a plethora of known effects that SCFAs have on myeloid cells. SCFAs induce chemotaxis in neutrophils through free fatty acid receptor

Methods

Results

Conclusion