Gut,Pharyngeal And Skin Microbiota In Psoriasis Patients:A Microbiome Research

Background: Psoriasis(PsO)is an immune-mediated chronic inflammatory condition,which severely affects the quality of life of patients.Although the pathogenesis of PsO is not entierly understood at present,it might be related to both genetic and environmental factors.Prior researches have demonstrated that the microbiota is involved in the pathogenesis of skin immune-inflammatory diseases,but its role in the pathogenesis of PsO remains unclear.In our study,we utilized 16 S r RNA gene amplicon sequencing to characterized the bacterial microbiota in PsO patients across different habitats(including the gut,pharynx,and skin)to gain a better understanding of the pathogenesis of PsO from a microbiology perspective.Part 1.Analysis of pharyngeal microbiota and its association with skin microbiota among different subtypes of psoriasis vulgarisObjective: To investigate the difference of pharyngeal microbiota among different subtypes of psoriasis vulgaris(PsV),including guttate psoriasis(GP),small plaque psoriasis(SPP),and large plaque psoriasis(LPP),and to analyze the correlation between pharyngeal and skin microbiota.Methods: Pharyngeal and skin swab samples from patients with GP,SPP,and LPP were collected and profiled by 16 S r RNA gene sequencing(V3–V4 region).The differences in the structure and composition of pharyngeal microbiota in different subtypes of psoriasis,and the correlation between pharyngeal microbiota and skin microbiota were analyzed.Results:(1)A total of 117 PsV patients were included and divided into GP(N=14),SPP(N=41),and LPP(N=62)subtypes.Pharyngeal microbiota from all patients was composed mainly of Firmicutes,Bacteroidota,Proteobacteria,and Fusobacteriota at the phylum level.(2)We observed a high similarity in pharyngeal microbial diversity and structure in different subtypes of PsV,but there were significant differences in the microbiota composition.In them,f＿Halomonadaceae,g＿Aliihoeflea,and g＿Halomonas were significantly enriched in the GP group.In the SPP group,f＿Lachnospiraceae,f＿Anaerovoracaceae,f＿unidentified＿Saccharimonadales,g＿Eubacterium＿nodatum＿group,g＿Lachnoanaerobaculum,g＿unidentified＿Saccharimonadales,and g＿Oribacterium were more abundant,while g＿Stomatobaculum was enriched in the LPP group.(3)In both the plaque psoriasis(including SPP and LPP patients)and GP,the relative abundances of g＿Prevotella＿9,g＿Parabacteroides,g＿Faecalibacterium,g＿Bacteroides,g＿Eubacterium＿eligens＿group,g＿Agathobacter,and g＿Alistipes were positively correlated between skin microbiota and pharynx microbiota.Part 2.The relationship between gut microbiota and psoriasis in patients with mild cognitive impairmentObjective: To investigate the difference of gut microbiota in healthy people and psoriasis patients with or without MCI.Method: A total of 125 patients with PsV and 37 healthy control(HC)were included.Cognitive function was assessed using the Montreal Scale(Mo CA)before treatment.Then,the patients were divided into psoriasis without cognitive impairment(PsO-NC,n=26)and psoriasis with mild cognitive impairment(PsO-MCI,n=99).Meanwhile,fresh fecal samples of the participants were collected for 16 S r RNA gene(V4-region)amplicon sequencing and bioinformatics analysis.Results:(1)Compared with HC,the α-diversity of gut microbiota in PsO-NC patients was increased(P < 0.05),but there was no difference when compared with PsO-MCI patients.There were significant differences in gut microbial composition and β-diversity among the PsO-NC,PsOMCI,and HC groups.(2)At the genus level,the relative abundance of Klebsiella in the PsOMCI group was increased,while that of g＿Blautia,g＿Lachnospira,g＿Lachnoclostridium and g＿Fusobacterium in the PsO-NC group were enriched.Certain dominant bacteria in gut microbiota were weakly correlated with clinical features and the Mo CA scale(P < 0.05).(3)PICRUSt functional analysis showed that multiple metabolic pathways and "glutamate synaptic" pathways were significantly reduced in the PsO-MCI group compared with the PsO-NC group.(4)ROC curve for two optimal random forest models based on 30 OTUs and 5 genera showed the AUC of 0.882 and 0.814,respectively.Part 3.Correlation Analysis of gut microbiota characteristics and the short-term response to IL-17 A inhibitors in psoriasisObjective: To investigate whether baseline gut microbiota can predict the short-term response to IL-17 A inhibitors in moderate-to-severe PsV.Method: 117 patients with moderate-to-severe PsV treated with secukinumab(SEC)or ixekizumab(IXE)were included,and the PASI75 response rate at 1 month of treatment was determined.Patients were divided into four groups: SEC responders(R-SEC),SEC non-responders(NR-SEC),IXE responders(R-IXE),and IXE non-responders(NR-IXE).Baseline fecal samples were collected for 16 S r RNA gene(V4-region)amplicon sequencing and bioinformatics analysis.Results:(1)The diversity and richness of the baseline gut microbiota were similar in the responders and non-responders who were treated with SEC or IXE for 1 month,and there was no significant difference in the overall microbial structure based on β-diversity analysis(P > 0.05).(2)In the SEC treatment cohort,compared with the non-responders,the relative abundance of f＿prevotellaceae was higher in the responders group,whereas the relative abundances of g＿Fusicatenibacter,g＿Eubacterium＿hallii＿group,g＿Ruminococcus＿torques＿group,and g＿Acidothermus were lower.The increased abundances of g＿Ruminococcus＿torques＿group and g＿Tyzzerella correlated with a lower PASI response rate.(3)In the IXE treatment cohort,only s＿Bacteroides＿stercoris was significantly enriched in the R-IXE group and lower in the NR-IXE group.The relative abundances of f＿Pasteurellaceae,g＿Haemophilus,s＿Haemophilus parainfluenzae,and s＿Bacteroides＿vulgatus were positively correlated with %improvement in PASI.Conclusion: 1.There is no significant difference in pharyngeal microbial community composition and structure among different subtypes of PsV,but certain different genera may play a potential role in shaping the clinical phenotype of PsV.The correlation between skin and pharyngeal microbiota may be related to the influence of dysmicrobial migration on the pathogenesis of psoriasis.2.Gut microbiota dysbiosis in patients with psoriasis and cognitive impairment.The identification model based on gut microbiota can well distinguish PsO-MCI patients in our cohort.The potential of gut microbiota as a novel biomarker for early screening and intervention in patients with psoriasis and cognitive impairment.3.Baseline gut microbial community diversity and structure were similar between short-term responders and non-responders to two IL-17 inhibitors in moderate-to-severe PsV patients,while certain differential microbiota may impact different responses to IL-17 A inhibitors.