Akkermansia muciniphila May Determine Chondroitin Sulfate Ameliorating or Aggravating Osteoarthritis

Abstract

Chondroitin sulfate (CS) has shown either ameliorating or aggravating effects on osteoarthritis (OA) in separately conducted clinical trials. Because CS is usually administered orally, it should be affected by or would impact on the individual gut microbiota. Evidence is accumulating that CS can nourish sulfatase-secreting bacteria (SSB) and sulfate-reducing bacteria (SRB). To decipher how can an individual gut microbiota determine the clinical values of CS for treatment on OA, we suggest here that CS would give distinct outcomes for OA treatment depending on Akkermansia muciniphila, a gut commensal probiotic bacterial species as optimal presence albeit also behaving as mucus-eroding bacteria (MEB) when abundant presence. Briefly, CS would ameliorate OA if A. muciniphila is present due to without overgrowth of SSB and SRB, whereas CS would aggravate OA if A. muciniphila is absent because of failure in or lack of competition with abundant SSB and SRB. By noting such a frequently ignored phenomenon, we urge the development of non-orally administering CS to minimize its side-effects and extend it to other medicinal applications.

Keywords: anti-inflammation; antibiotic; chondroitin sulfate; gut microbiota; opportunistic infection; osteoarthritis; pro-inflammation; probiotic.

Figure 1

Changes in the gut microbiota profiles of mice fed ad libitum (AL) and chondroitin sulfate (CS) (n = 3 for mice fed CS; n = 2 for mice fed AL; CS.RA, CS.NM, and CS.HL represent three mice fed CS; AL1 and AL2 represent two mice fed AL). (A) CS-induced gut microbiota shifts that varied in individual mice. (B) Unbalanced gut symbionts with more SSB+SRB than MEB species that aggravate OA due to insufficient A. muciniphila; (C) balanced gut symbionts in germ-free conditions or with commensal diversity that ameliorate OA because of no gut microbiota interference. (D) Unbalanced gut symbionts with more MEB than SSB+SRB that ameliorate OA when the abundance of A. muciniphila is optimal or aggravate OA if the colonization of A. muciniphila is excessive. The relative abundance of bacteria is represented by red (increased) to blue (decreased) colors accounting for Z values from −1.5 to 1.5.