Worldwide presence of Blastocystis in the human gut microbiome is linked to healthier dietary regimes and lower body mass index

The human body is inhabited by a community of diverse bacteria, archaea, viruses, fungi, and microeukaryotes, collectively called the human microbiome, that impact human health. Shotgun metagenomic sequencing enables high-resolution profiling of all members of the community. While the bacterial constituents have been investigated extensively, organisms from other domains, such as eukaryotes, are currently underexplored. Blastocystis spp. is a common eukaryotic protist that lives in the gastrointestinal tract of humans and other animals. The ecological and clinical significance of Blastocystis is still controversial, as it has been associated both with gastrointestinal symptoms and has been found in asymptomatic individuals. We performed a large-scale data harmonization and analysis of more than 50,000 metagenomic samples (34,687 from the ZOE PREDICT Studies, 13,928 from 68 public studies on humans, and 4,623 animal samples from 50 public studies) to investigate Blastocystis presence in the gut microbiome. Our results suggest a potentially favorable role for Blastocystis. We observed a worldwide presence of Blastocystis among healthy individuals with prevalence variability linked to host age, lifestyle, and geographical provenance. We established a dose-dependent coupling of Blastocystis carriage and diet quality, showing that Blastocystis-positive individuals tended to consume healthier, less-processed, fiber-enriched foods. Moreover, we show that the presence of Blastocystis was associated with favorable near-term fasting and postprandial cardiometabolic markers, such as lower GlycA and higher HDL. Finally, we reveal through meta-analysis a robust and reproducible association between the presence of Blastocystis and a lower body mass index, as well as reduced risk for inflammatory bowel diseases, colorectal cancer, and diabetes. Overall, the widespread presence of Blastocystis among healthy individuals suggests that, although associated with disease in certain conditions, it could be a non-pathogenic member of the gut microbiome. Further genomic studies are needed to unravel the specific role of Blastocystis subspecies in human health and disease. Finally, our work serves as an example of how shotgun metagenomic datasets can help investigate the non-bacterial components of the human microbiome.