Evidence for dysbiosis in the gut microbiome of patients with systemic mastocytosis

Abstract

Background: Limited research studies have investigated the role of the gut microbiome in systemic mastocytosis (SM), which is characterized by an aberrant expansion of clonal mast cells in specific tissues including the skin, marrow, liver, and the gastrointestinal tract. Objectives: We sought to investigate the relationship between the intestinal microbiome and clinical manifestations of SM. Methods: The V4 region of the 16S rRNA gene was sequenced from stool samples of 22 patients with SM and 9 healthy controls. Microbial community composition, diversity, and functional genes inferred from 16S rRNA gene sequences were analyzed. ClinicalTrials.gov Identifier NCT00044122. Results: Changes in microbial community composition were associated with SM, KIT D816V, and tryptase (PERMANOVA, P = .004, P = .05, P = .005, respectively). The differences with SM were driven by the composition of Firmicutes (P = .04) and an increase in Bacteroidetes abundance (P = .04). Predicted functions of the gut microbiome suggested that there were differences in metabolite profiles, including short-chain fatty acids, increased virulence factors, and decreased bacterial defense mechanisms in patients with SM. Dietary components were associated with symptoms, quality of life, and markers of mast cell activation and inflammation, as well as changes in microbial composition and predicted function in patients with SM. Conclusions: Dysbiosis of the gut microbiome is evident in patients with SM and is seemingly associated with mast cell activation. In addition, diet may further alter microbial composition and metabolism in the gut of patients with SM