Full-repertoire comparison of the microscopic objects composing the human gut microbiome with sequenced and cultured communities

The study of the human gut microbiome is essential in microbiology and infectious diseases as specific alterations in the gut microbiome might be associated with various pathologies, such as chronic inflammatory disease, intestinal infection and colorectal cancer. To identify such dysregulations, several strategies are being used to create a repertoire of the microorganisms composing the human gut microbiome. In this study, we used the “microscomics” approach, which consists of creating an ultrastructural repertoire of all the cell-like objects composing stool samples from healthy donors using transmission electron microscopy (TEM). We used TEM to screen ultrathin sections of 8 resin-embedded stool samples. After exploring hundreds of micrographs, we managed to elaborate ultrastructural categories based on morphological criteria or features. This approach explained many inconsistencies observed with other techniques, such as metagenomics and culturomics. We highlighted the value of our culture-independent approach by comparing our microscopic images to those of cultured bacteria and those reported in the literature. This study helped to detect “minimicrobes” Candidate Phyla Radiation (CPR) for the first time in human stool samples. This “microscomics” approach is non-exhaustive but complements already existing approaches and adds important data to the puzzle of the microbiota.