Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease

Abstract

Objective: To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA).

Methods: High-throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids.

Results: The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis.

Conclusion: Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis-PsA pathogenesis and the associated immune response merits further study.

Figure 1. Bacterial taxa differences between PsA, Ps and healthy controls

Bacterial taxa significantly enriched in healthy controls (HLT) as compared to psoriatic arthritis (PsA) patients were detected by LefSe (P <0.05, LDA >2logs) and after false-discovery rate (FDR). (A) Overall, no taxon was found to be enriched in PsA (red bars) compared to HLT (blue bars) or (B) Ps patients (green bars). Taxa are arranged in descending order according to their LDA score and marked with an asterisk (*) when significance remained after FDR correction. (C) Taxa differentiating PsA from Ps samples. (D) Box-plots with relative abundance (parts per unit) of specific taxa underrepresented in PsA and Ps subjects. Only those with statistical differences after FDR correction are shown.

Figure 2. Decreased operational taxonomic units (OTUs) in PsA and Ps gut microbiota

Several members of the gut microbial communities are underrepresented in PsA and Ps patients at the OTU level. (A) Bacterial OTUs significantly enriched in healthy controls (blue bars) as compared to PsA (red bars) and (B) Ps patients (green bars) were detected by LefSe. Those significant OTUs with q<0.2 after false-discovery rate (FDR) analysis are indicated by asterisks (*). (C) OTUs with distinct abundance in PsA and Ps. (D) Box-plots with relative abundance (parts per unit) of those OTUs marked with * in A–C.

Figure 3. Gut lumen and serum sIgA, RANKL, OPG and S100 levels

(A) Levels of gut lumen sIgA are higher in PsA patients compared to controls, while measurements in serum revealed no differences among groups. (B) Fecal RANKL were not measurable in most PsA patients, while serum levels were similar among groups. (C) Levels of OPG in fecal samples were higher in Ps vs controls, but similar to those in PsA. (D) Serum S100 levels were significantly higher in Ps compared to PsA and controls. Note: Fecal samples were not available for fecal measurements for two healthy subjects. Fecal RANKL, OPG and S100 were not available in one PsA patient.

Figure 4. Fecal levels of short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs)

(A) The levels of SCFAs (Acetate, Butyrate, Iso-Butyrate, Propionate, Valerate, Iso-Valerate) and MCFAs (Hexanoate and Heptanoate) were quantified in fecal samples of all groups. While no difference were found in any of the SCFAs, both MCFAs levels were significantly lower in PsA and Ps samples, compared to healthy controls (P<0.01 and P<0.05, respectively). (B) Total levels of fatty acids (CFAs) were similar among groups.

Figure 5. Correlations between gut microbiota and metadata

Relative abundance of gut microbiota was correlated with levels of various proteins and fatty acids in serum and/or fecal samples. Heatmaps showing correlations between patient metadata and intestinal microbiota at (A) genus level or (B) OTU level. Circle sizes and color intensity represent magnitude of correlation. Blue circles = positive correlations; red circles = negative correlations.