Gut and Cutaneous Microbiome Featuring Abundance of Lactobacillus reuteri Protected Against Psoriasis-Like Inflammation in Mice

Abstract

Background

Psoriasis is a chronic autoinflammatory skin disease, and its aetiology remains incompletely understood. Recently, gut microbial dysbiosis is found to be tightly associated with psoriasis.

Objective

We sought to reveal the causal role of gut microbiota dysbiosis in psoriasis pathogenesis and investigate the protective effect of healthy commensal bacteria against imiquimod -induced psoriasis-like skin response.

Methods

By using fecal microbial transplantation (FMT), 16S rRNA gene-based taxonomic profiling and Lactobacillus supplement, we have assessed the effect of FMT from healthy individuals on psoriasis-like skin inflammation and associated immune disorders in imiquimod-induced psoriasis mice.

Results

Here, by using psoriasis mice humanized with the stools from healthy donors and psoriasis patients, the imiquimod-induced psoriasis in mice with psoriasis patient stool was found to be significantly aggravated as compared to the mice with healthy donor stools. Further analysis showed fecal microbiota of healthy individuals protected against Treg/Th17 imbalance in psoriasis. Moreover, we found the gut and skin microbiome in mice receipted with gut microbiota of healthy individuals (HD) differed from those of mice receipted with gut microbiota of psoriasis patients (PSD). 16S rRNA sequencing revealed that Lactobacillus reuteri was greatly enriched in fecal and cutaneous microbiome of HD mice as compared to PSD mice. Intriguingly, supplement with Lactobacillus reuteri was sufficient to increase the expression of anti-inflammatory gene IL-10, reduce Th17 cells counts and confer resistance to imiquimod-induced inflammation on the mice with gut microbiota dysbiosis.

Conclusion

Our results suggested that the gut microbiota dysbiosis is the potential causal factor for psoriasis and the gut microbiota may serve as promising therapy target for psoriasis patients.

Keywords:

• gut microbiota
• cutaneous microbiome
• psoriasis
• fecal microbiota transplantation
• Lactobacillus reuteri
• Th17

Data Sharing Statement

All the data supporting the findings of this study are available within the article and its Supplementary Materials.

Ethics Approval and Consent to Participate

Animal care and experiments were carried out in strict accordance with the Animal Care and Use Guide and approved by the ethics committee of Fudan University.

Disclosure

The authors declare no conflicts of interest.

Additional information

Funding

This work was supported by grants from National Natural Science Foundation of China (81872245 and 81803601), Research Project of Shanghai Municipal Health Commission (20214Y0326), Open Research Fund of State Key Laboratory of Genetic Enigineering, Fudan Univeristy (SKLGE-2112), Natural Science Research Project of Shanghai Minhang District (No.2020MHZ090 and No.2021MHZ086) and High-level Backbone Physicians Training Programme of Minhang District (2020MZYS18).