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Background <p>The contribution of the gut microbiome to the pathogenesis of psoriasis remains a subject of debate, with inconsistent findings across studies likely confounded by environmental factors. This study aimed to statistically disentangle the effects of a shared household environment from disease-specific microbial signatures in psoriasis. Our objective was to identify novel, multi-kingdom biomarkers, encompassing bacteria and viruses, that hold significant diagnostic and therapeutic potential.</p> Methods <p>We conducted a nested case-control study, performing shotgun metagenomic sequencing on stool samples from 143 participants. The cohort comprised 98 psoriasis patients, 28 healthy cohabiting relatives, and 17 unrelated healthy controls. A comprehensive multi-kingdom analysis of bacteria, viruses, and their associated metabolic pathways was implemented. To ensure the robustness of our findings, a two-stage discovery-validation strategy was employed to identify distinct microbial features associated with psoriasis.</p> Results <p>Our analysis revealed that the shared household environment was the predominant factor shaping the overall gut microbiome structure. Despite this strong confounding effect, we successfully identified a novel bacterial species, <i>Fimenecus sp000432435</i>, as a robust biomarker for psoriasis, achieving an area under the curve (AUC) of 0.84. Genomic functional prediction indicated that this species encodes pathways with the potential for B-vitamin and secondary bile acid biosynthesis. Furthermore, characterization of the gut virome identified five disease-associated bacteriophages. Among these, <i>vBin_422</i> exhibited a significant negative correlation with the abundance of <i>Fimenecus sp000432435</i>, suggesting a potential ecological interaction. Notably, the biotin biosynthesis pathway was negatively correlated with disease severity, whereas specific viral taxa showed a positive correlation with systemic inflammatory markers within the patient cohort.</p> Conclusions <p>Controlling for environmental confounders reveals that psoriasis is associated with sparse but distinctmicrobial signatures rather than broad dysbiosis. <i>Fimenecus sp000432435</i> is a promising candidate for non-invasive diagnostics, while the characterized virome opens new therapeutic avenues targeting bacteriophage-bacteria interactions in psoriasis management.</p> Trial registration <p>ChiCTR-IOR-17011075. Registered 6 April 2017, <a href="http://www.chictr.org.cn/showproj.aspx?proj=17334">http://www.chictr.org.cn/showproj.aspx?proj=17334</a></p>

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Disentangling environmental and disease-specific signatures in the gut microbiome of psoriasis: discovery of Fimenecus sp. as a novel biomarker and characterization of the gut virome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月25日

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  • Jingwen Deng,
  • Qinwei Qiu,
  • Shuyan Ye,
  • Jingjie Yu,
  • Danni Yao,
  • Hao Deng,
  • Chengrui Wang,
  • Lijuan Han,
  • Yusheng Deng,
  • Yang Chen,
  • Yanmin Liu,
  • Cuihua Liu,
  • Xiaoxiao Shang,
  • Xiaodong Fang,
  • Chuanjian Lu

摘要

Background

The contribution of the gut microbiome to the pathogenesis of psoriasis remains a subject of debate, with inconsistent findings across studies likely confounded by environmental factors. This study aimed to statistically disentangle the effects of a shared household environment from disease-specific microbial signatures in psoriasis. Our objective was to identify novel, multi-kingdom biomarkers, encompassing bacteria and viruses, that hold significant diagnostic and therapeutic potential.

Methods

We conducted a nested case-control study, performing shotgun metagenomic sequencing on stool samples from 143 participants. The cohort comprised 98 psoriasis patients, 28 healthy cohabiting relatives, and 17 unrelated healthy controls. A comprehensive multi-kingdom analysis of bacteria, viruses, and their associated metabolic pathways was implemented. To ensure the robustness of our findings, a two-stage discovery-validation strategy was employed to identify distinct microbial features associated with psoriasis.

Results

Our analysis revealed that the shared household environment was the predominant factor shaping the overall gut microbiome structure. Despite this strong confounding effect, we successfully identified a novel bacterial species, Fimenecus sp000432435, as a robust biomarker for psoriasis, achieving an area under the curve (AUC) of 0.84. Genomic functional prediction indicated that this species encodes pathways with the potential for B-vitamin and secondary bile acid biosynthesis. Furthermore, characterization of the gut virome identified five disease-associated bacteriophages. Among these, vBin_422 exhibited a significant negative correlation with the abundance of Fimenecus sp000432435, suggesting a potential ecological interaction. Notably, the biotin biosynthesis pathway was negatively correlated with disease severity, whereas specific viral taxa showed a positive correlation with systemic inflammatory markers within the patient cohort.

Conclusions

Controlling for environmental confounders reveals that psoriasis is associated with sparse but distinctmicrobial signatures rather than broad dysbiosis. Fimenecus sp000432435 is a promising candidate for non-invasive diagnostics, while the characterized virome opens new therapeutic avenues targeting bacteriophage-bacteria interactions in psoriasis management.

Trial registration

ChiCTR-IOR-17011075. Registered 6 April 2017, http://www.chictr.org.cn/showproj.aspx?proj=17334