Bacillus Subtilis–Derived Exopolysaccharide Halts Depigmentation and Autoimmunity in Vitiligo

Ahmed A. Touni, Sara Muttar, Zoya Siddiqui, Rohan S. Shivde, Emily Krischke, Digvijay Paul, Mohamed A. Youssef, Anne I. Sperling, Rasha Abdel-Aziz, Hossam Abdel-Wahab, Katherine L. Knight, I. Caroline Le Poole*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Vitiligo has a complex multifactorial etiology involving a T-cell–mediated autoimmune response to cutaneous melanocytes. Microbial dysbiosis has been assigned a contributing role in vitiligo etiology. Treating vitiligo can be a challenging task, and finding novel treatment approaches is crucial. In this study, we tested exopolysaccharides (EPSs) isolated from Bacillus subtilis as a microbiome-based therapy. Vitiligo-prone h3TA2 mice were treated by weekly intraperitoneal EPS injection for 18 weeks. Depigmentation was evaluated over time, measuring immune responses at end point. EPS treatment significantly limited the rate of depigmentation. The abundance of cutaneous T cells, specifically CD8+ cytotoxic T cells, was reduced, whereas regulatory T cells were more abundant in the skin of treated mice than in untreated mice. Moreover, EPS treatment was associated with increased numbers of splenic M2 macrophages, elevated splenic indoleamine 2,3-dioxygenase expression, and a systemic cytokine shift toward a type 2 pattern of cytokines. Importantly, splenocytes retrieved from EPS-treated mice were less responsive to cognate tyrosinase peptide, as demonstrated by limited release of IFN-γ and other inflammatory cytokines. In summary, EPS isolated from B subtilis interfered with T-cell–mediated depigmentation in the h3TA2 mouse model of vitiligo, suggesting that B subtilis EPS could serve as a novel treatment entity for vitiligo.

Original languageEnglish (US)
JournalJournal of Investigative Dermatology
DOIs
StateAccepted/In press - 2025

Funding

AAT was the recipient of a joint-supervision scholarship from the Ministry of Higher Education and Scientific Research. ICLP is the principal investigator of Leo Foundation research award L-OC-23-001288. SM held a Summer Research Scholars Program scholarship from the Northwestern Feinberg School of Medicine. These contributions are gratefully acknowledged. Graphical abstract was generated in BioRender.com. Conceptualization: ICLP, KLK, AAT; Data Curation: AAT, SM, ZS, RSS; Formal analysis: AAT, ICLP, RSS, EK; Funding Acquisition: AAT, ICLP; Investigation: AAT, SM, ZS, RSS, MAY, DP, EK; Methodology: AAT, RSS, ICLP; Project Administration: ICLP; Resources: KLK, ICLP; Software: AAT, RSS, DP, EK, MAY; Supervision ICLP, RA-A, HA-W; Validation: ICLP, HA-W, RA-A, AIS; Visualization: AAT, SM, ZS, EK, DP; Writing \u2013 Original Draft Preparation: AAT, SM, ICLP; Writing \u2013 Review and Editing: KLK, AIS, HA-W, RA-A AAT was the recipient of a joint-supervision scholarship from the Ministry of Higher Education and Scientific Research, Egypt. ICLP is the PI of Leo Foundation research award L-OC-23-001288. SM held a Summer Research Scholars Program scholarship from the Northwestern Feinberg School of Medicine. These contributions are gratefully acknowledged.

Keywords

  • Bacillus subtilis
  • Exopolysaccharide
  • Microbiome
  • Tregs
  • Vitiligo

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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