Glucose metabolism's impact on Blastocystis presence in the human gut

BACKGROUND AND AIMS: The role of Blastocystis spp. parasite in human health remains debated. Recent literature associates it with a healthy gut and lifestyle. Evidence suggests that Blastocystis spp. could enhance glucose homeostasis, although Blastocystis spp. is considered to be epiphenomena for a lifestyle. Moreover, some subtypes seem to have a beneficial impact while others would hinder the host's health. Here, we explore the complex link between Blastocystis spp. and glucose metabolism parameters. METHODS: We explored shotgun metagenomic profiles of the gut microbiota from fecal samples associated with glucose metabolism parameters in 4 independent cohorts (CGM, n = 65; IMAGEOMICS, n = 1030; PECT, n = 841 and MEIFLO, n = 22), using microbiome compositional analysis methodology. We leverage data from MEIFLO, a recent clinical trial conducted in patients recently diagnosed with type 2 diabetes (T2D), to investigate how metformin-induced improvement in glucose metabolism influences gut microbiota composition, using Linear Models for Differential Abundance. We studied possible associations of Blastocystis spp. with leukocyte telomere length. RESULTS: We confirmed and extended the relationship between glucose homeostasis and Blastocystis spp. and subtypes ST1 and ST4, showing its association with glucose and insulin levels in all cohorts. Importantly, we observed that glucose homeostasis may shape Blastocystis spp. abundance in the gut, rather than the reverse, based on clinical trial data showing that metformin (not placebo) increased Blastocystis spp. in recently diagnosed T2D patients. We identify Blastocystis as one of the microbial genera most strongly and directly associated with telomere length in the IMAGEOMICS cohort. CONCLUSIONS: The direct relation between Blastocystis and telomere length aligns with the observed inverse associations of glucose levels with telomere length, and glucose levels with Blastocystis. We propose that Blastocystis may be associated with healthy glucose metabolism as an outcome and potentially serve as an indicator of improved metabolic health.