Myxobacteria are Gram-negative, spore-forming predatory bacteria isolated from diverse environmental samples that feed on other microbes for their survival and growth. However, no reports of cultured representatives from the human gut have been published to date, although previous investigations have revealed the presence of myxobacterial operational taxonomic units (OTUs) in skin and fecal samples. In this study, three myxobacterial strains designated as O35, O15, and Y35 were isolated and purified from fecal samples of two inflammatory bowel disease (IBD) patients. The 16S rRNA gene sequence analysis and phylogeny identified the strains as Myxococcus spp. belonging to two different clades. Genome-based phylogeny and overall genome-related indices, i.e., average amino acid identity and percentage of conserved proteins, confirmed the heterogeneity within the genus and placed the three strains within two different clades separated at the level of different genera. Digital DNA-DNA hybridization and average nucleotide identity values indicated that they belonged to two novel Myxococcus spp. The analysis of meta-barcoding data from IBD and control cohorts detected OTU lineages closely affiliated to the three novel strains. Based on evidence from detailed structural and functional genomics, we propose the novel species Myxococcus faecalis sp. nov. O35(T) and a new genus Pseudomyxococcus gen. nov. to accommodate the novel species Pseudomyxococcus flavus sp. nov. Y35(T). Overall, these findings provide new information about the occurrence of myxobacteria in the human gut and lay the foundations for a new classification scheme for myxobacterial taxa.IMPORTANCEMyxobacteria have been described from a variety of niches ranging from terrestrial to marine habitats and are known to harbor a diverse portfolio of bioactive molecules. However, to date, there has been no report of isolating culturable representatives from the human gut. This study describes novel myxobacteria from the human gut based on phylogenomics and phenotypic description. The findings are complemented by sequence-based data, wherein operational taxonomic unit (OTU) lineages closely affiliated with the isolated strains have been identified, thus opening a Pandora's box of opportunities for research into the microbial ecology and functional potential of these taxa in the gut ecosystem. Additionally, the study also seeks to establish a new systematic framework, expanding our understanding of myxobacterial taxonomy.