Background/Purpose: Relapsing polychondritis (RP) is an inflammatory disease that affects cartilaginous tissues of the body and the clinical manifestations and disease courses vary considerably among patients. We previously reported that auricular involvement and respiratory involvement were mutually exclusive in the incidence (Arthritis Rheumatol. 2018, Medicine. 2018). Serum MMP3 concentrations correlated with IL1β and IL6 mRNA expressions of peripheral blood mononuclear cells (PBMCs) only in RP patients with respiratory involvement (ACR Open Rheumatol. 2021). We further found that a short-chain fatty acid (SCFA) propionate-producing gut microbes increased in the intestine of RP patients compared with healthy individuals (Plos One. 2018). SCFAs were suggested to affect systemic inflammation through regulation of T cell differentiation in mouse models. Based on these data, in the current study, we compared bacterial abundance and gene functions between RP patients with and without respiratory involvement using software QIIME and LEfSe.

Methods: Metagenomic analysis of the gut microbiome was performed by sequencing of 16S rRNA gene in 21 RP patients. In the patients, 11 patients (52%) had respiratory involvement (termed as Resp group and other 10 patients were termed as Non-resp group). We extracted mRNA from freshly isolated and cultured PBMCs and measured a panel of cytokine gene expressions. We next evaluated serum MMP3 using an ELISA kit.

Results: No significant differences were observed in age, age at onset, gender, and disease duration between Resp and Non-resp groups. In the metagenomic analyses, we did not find significant differences in the OTU numbers and alpha diversity indexes between the two groups. In Non-resp group, family Veillonellaceae, family Ruminococcaceae, species Bifidobacterium bifidum, and species Faecalibacterium prausnitzii, all of which were reported to associate with SCFA production, were prevalent in the intestine. Family Leuconostocaceae and species Streptococcus anginosus were predominant in the bacterial composition of Resp group. As expected, bacterial gene functions of a SCFA butyrate synthesis pathway were prevalent in gut microbes of Non-resp group. We did not find any significant correlations among relative abundance of bacterial taxa, PBMC cytokine mRNA expressions, and serum MMP3.

Conclusion: These data suggest that the characteristic composition of gut microbes, probably through their production of SCFAs, may associate with not only disease onset but also progression processes of RP. Further, from the data of gut bacterial gene function, we speculate that each SCFA, propionate and butyrate, may be distinctively associated with clinical phenotypes of RP.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/gut-microbe-metabolite-short-chain-fatty-acids-may-associate-with-development-of-respiratory-involvement-in-patients-with-relapsing-polychondritis/