Small intestinal derived Prevotella histicola simulates biologic as a therapeutic agent

Sci Rep. 2024 Nov 25;14(1):29217. doi: 10.1038/s41598-024-80635-4.

Abstract

A role of gut microbiome in pathogenesis as well as response to treatment is documented in rheumatoid arthritis. Using a novel duodenal derived Prevotella histicola strain MCI 001, we have shown that it suppresses disease progression in a collagen-induced arthritis (CIA), a model for rheumatoid arthritis (RA) using humanized mice expressing HLA-DQ8 gene in the absence of endogenous class II genes. Here we compared efficacy of P. histicola MCI 001 with tumor necrosis factor inhibitor (TNFi) for treating arthritis. DQ8 arthritic mice treated with P. histicola by oral gavage or TNFi, were compared for disease onset, incidence and severity. We demonstrate that oral treatment with P. histicola mimics treatment with TNFi in arthritic DQ8 mice. A pangenome comparison of our P. histicola MCI 001 with its closest available neighbors depicted it as a novel strain with unique gene sequences that may contribute to immune modulatory effects. Notably, it possesses a unique sequence of an outer membrane protein, BtuB, which is involved in vitamin B12 transport. Our data indicate that P. histicola MC001 is an attractive candidate to prevent the progression of disease in RA patients with ongoing disease.

Keywords: Bio-therapeutic; Microbiome; Outer membrane protein; Prevotella histicola; Rheumatoid arthritis; Small intestine; TNF-inhibitor.

MeSH terms

  • Animals
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / microbiology
  • Arthritis, Rheumatoid* / drug therapy
  • Arthritis, Rheumatoid* / microbiology
  • Disease Models, Animal
  • Gastrointestinal Microbiome* / drug effects
  • HLA-DQ Antigens / genetics
  • Humans
  • Intestine, Small / drug effects
  • Intestine, Small / microbiology
  • Male
  • Mice
  • Prevotella* / drug effects
  • Prevotella* / genetics
  • Tumor Necrosis Factor Inhibitors / pharmacology
  • Tumor Necrosis Factor Inhibitors / therapeutic use

Substances

  • Tumor Necrosis Factor Inhibitors
  • HLA-DQ8 antigen
  • HLA-DQ Antigens

Supplementary concepts

  • Prevotella histicola