Influence of biological treatments on intestinal microbiota of psoriasis patients

To the Editor: Psoriasis is a common, chronic inflammatory skin disease occurring worldwide and presenting at any age.1 Biologics are the most important therapeutic advances in psoriasis treatment.2 With the development of 16S rRNA sequencing technology, the association between psoriasis and intestinal flora has been gradually revealed. Some bacteria secrete short-chain fatty acids (SCFAs) with anti-inflammatory properties, serving as active microbial metabolites that regulate the function of immune cells in the intestine and other tissues.3 However, the impact of biological treatment on gut microbiota and related functional changes in psoriasis patients remains unclear. Our study aimed to explore the effects of biological treatments on the intestinal microbiota of psoriasis patients. This research was reviewed and approved by the Ethic Committee of The First Affiliated Hospital of Chongqing Medical University (No. 2023-433). Patients have given written informed consent to publication of their case details. Inclusion criteria and exclusion criteria are shown in Supplementary Materials, https://links.lww.com/CM9/C83. Finally, a total of 181 plaque psoriasis vulgaris patients were enrolled, and their fecal samples were collected. Participant's characteristics are presented in Supplementary Table 1, https://links.lww.com/CM9/C83. Biologics included tumor necrosis factor (TNF)-α inhibitors (adalimumab), interleukin (IL)-17A inhibitors (secukinumab and ixekizumab), IL-12/23 inhibitors (ustekinumab), and IL-23 inhibitors (guselkumab). Age, sex, and body mass index (BMI) were matched in non-bio-treated and bio-treated group Supplementary Table 1, https://links.lww.com/CM9/C83. According to our findings, there were no significant differences in alpha-diversity between the bio-treated and non-bio-treated groups Supplementary Figure 1A–E, https://links.lww.com/CM9/C83. Furthermore, no significant statistical differences in terms of the Firmicutes/Bacteroidetes (F/B) ratio between these two groups Supplementary Figure 1F, https://links.lww.com/CM9/C83. No significant clustering was observed based on Bray-Curtis dissimilarity Supplementary Figure 1G,H, https://links.lww.com/CM9/C83. We found that the fecal microbiota in both groups appeared to be dominated by Firmicutes and Actinobacteriota at the phylum level, and by Blautia and Faecalibacterium at the genus level Supplementary Figure 1I,J, https://links.lww.com/CM9/C83. To detect the specific bacteria's discrepancy, we analyzed the gut microbiota at genus level. Our results revealed a significantly higher relative abundance of Coprococcus (P = 0.0450) and Adlercreutzia (P = 0.0062), and a significantly lower relative abundance of Dialister (P = 0.0189), Veillonella (P = 0.0308), Eggerthella (P = 0.0102), and Erysipelatoclostridium (P = 0.0440) were observed in the bio-treated group Supplementary Figure 2A, https://links.lww.com/CM9/C83. We then conducted LEfSe comparison of these two groups. The structure and predominant bacteria of the microbiota were represented in a cladogram. The greatest difference in taxa from phylum to genus level was identified by the linear discriminant analysis (LDA) score. Coprococcus were enriched in fecal microbiota in the bio-treated group, while the top two in non-bio-treated group were Dialister and Veillonella at the genus level Supplementary Figure 2B,C, https://links.lww.com/CM9/C83. Heat map showed Enterococcus decreased in the bio-treated group Supplementary Figure 2D,E, https://links.lww.com/CM9/C83. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways are shown in Supplementary Figure 3, https://links.lww.com/CM9/C83. Subgroups (IL-12/23i, IL-17i, and IL-23i) of the bio-treated group were then analyzed. Results revealed that although the Sobs index had no significant differences at Operational Taxonomic Units (OTU) level, Chao index between the IL-12/23i group and IL-17i group displayed a significant difference in genus level (P = 0.0247) Supplementary Figure 4A–E, https://links.lww.com/CM9/C83. Beta-diversity analysis based on Principal Co-ordinates Analysis (PCoA) showed no significant differences among the three bio-treated groups. The F/B ratio of IL-12/23i, IL-17i, and IL-23i groups were decreased in turn, but there were no significant differences between the three groups Supplementary Figure 4F, https://links.lww.com/CM9/C83. The fecal microbiota in the three bio-treated groups appeared to be dominated by Firmicutes at phylum level, and by Blautia at genus level Supplementary Figure 4G–J, https://links.lww.com/CM9/C83. At genus level, the IL-12/23i group had a significantly higher relative abundance of Megamonas (P = 0.0408); the IL-17i group had a significantly higher relative abundance of, Rothia (P = 0.0216), and Granulicatella (P = 0.0495); and IL-23i had a significantly higher relative abundance of Alistipes (P = 0.0361), Oscillibacter (P = 0.0451) and Colidextribacter (P = 0.0453) Supplementary Figure 5A, https://links.lww.com/CM9/C83. Megamonas was enriched in the fecal microbiota of the IL-12/23i group, Rothia in the IL-17i group, and Alistipes in the IL-23i group in genus level Supplementary Figure 5B,C, https://links.lww.com/CM9/C83. The heatmap indicated an increase in Sarcina in the IL-23i group and an increase in CAG-352 in the IL-12/23i group compared with the other two groups at the genus level. Supplementary Figure 5D,E, https://links.lww.com/CM9/C83. To understand whether severity of skin lesions affects the changes in intestinal flora composition and abundance in psoriasis patients, we divided all patients into four different disease severity groups according to psoriasis area and severity index (PASI) score: mild (PASI 6 months showed the most significant increase in the relative abundance of Butyricimonas (P = 0.0469) Supplementary Figure 8I, J, https://links.lww.com/CM9/C83. The Redundancy analysis/Canonical Correlation Analysis (RDA/CAA) environmental factor analysis are shown in Supplementary Figure 9, https://links.lww.com/CM9/C83. The 16s rRNA sequencing data of this article were deposited in GenBank (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1014805). Adlercreutzia is an anti-inflammatory bacterium, and Butyricicoccus is a butyrogenic bacterium. SCFAs play an anti-inflammatory role by down-regulating inflammatory cytokines such as IL-6 and IL-8.4 In this study, as the PASI IR score increases, the relative abundance of Adlercreutzia and Butyricicoccus decreases in turn. The presence of butyrogenic bacteria seems to correlate with the intensity of the inflammatory response. A stronger inflammatory response in psoriasis seems linked to a higher abundance of anti-inflammatory gut bacteria, suggesting that gut microbiota could indicate the severity of inflammation. Our findings revealed that the gut microbiota of psoriasis patients with different lesion severity had different characteristics, and biological treatment changed the composition and structure of intestinal flora. There was a certain correlation between PASI IR and butyrogenic bacteria in psoriasis patients. Butyrogenic bacteria produce SCFAs with anti-inflammatory properties and modulate immune cell function in the intestine and other tissues. They might play a role in the intestinal immunoinflammatory response of psoriasis and could serve as a biomarker for its severity. However, further research into their mechanisms with larger sample sizes is necessary to strengthen the findings. In the course of psoriasis biological treatment, adjusting diet and lifestyle habits and paying attention to the increase and decrease of beneficial biomarkers of intestinal flora can contribute to disease prognosis and individualized treatment. Acknowledgment The authors are grateful to Ying Chen for her kindly help in this study. Funding This work was funded by grants from the National Natural Science Foundation of China (No. NSFC 82103733) and Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJQN202100412). Conflicts of interest None.