A study reveals that a significant portion of the human intestinal microbiota can be cultured, challenging the long-held belief that many bacteria are 'unculturable'. Using a novel workflow combining targeted phenotypic culturing with large-scale whole-genome sequencing, phylogenetic analysis, and computational modeling, researchers isolated 137 bacterial species from healthy individuals. These species included 45 candidate novel species, 20 candidate novel genera, and 2 candidate novel families. The study found that at least 50–60% of the bacterial genera in the intestinal microbiota produce resilient spores, which are specialized for host-to-host transmission. This discovery highlights the importance of spore formation in the transmission and persistence of intestinal bacteria. The research also demonstrated that spore-forming bacteria are more resistant to environmental stresses, such as ethanol, than non-spore-forming bacteria. Spore-forming bacteria, including the pathogen Clostridium difficile, can survive for extended periods in the environment, facilitating their transmission between individuals. The study identified that spore-forming bacteria are more diverse than non-spore-forming bacteria and that their relative abundance can vary over time. These findings suggest that spore-forming bacteria play a significant role in the heritability of the human microbiota. The study's approach enabled the large-scale culturing, archiving, and genome sequencing of previously unculturable bacteria, providing new insights into the functional attributes of the human microbiota. The results challenge the notion that the majority of the intestinal microbiota is unculturable and highlight the importance of spore formation in the transmission and persistence of intestinal bacteria. The study also identified a genomic signature associated with spore formation, which can be used to predict the sporulation capabilities of bacterial species from diverse environments. This signature includes 66 conserved genes linked to an ethanol-resistance phenotype, which allows for the accurate prediction of sporulation capabilities. The findings have important implications for understanding the transmission and inheritance of the human microbiota.A study reveals that a significant portion of the human intestinal microbiota can be cultured, challenging the long-held belief that many bacteria are 'unculturable'. Using a novel workflow combining targeted phenotypic culturing with large-scale whole-genome sequencing, phylogenetic analysis, and computational modeling, researchers isolated 137 bacterial species from healthy individuals. These species included 45 candidate novel species, 20 candidate novel genera, and 2 candidate novel families. The study found that at least 50–60% of the bacterial genera in the intestinal microbiota produce resilient spores, which are specialized for host-to-host transmission. This discovery highlights the importance of spore formation in the transmission and persistence of intestinal bacteria. The research also demonstrated that spore-forming bacteria are more resistant to environmental stresses, such as ethanol, than non-spore-forming bacteria. Spore-forming bacteria, including the pathogen Clostridium difficile, can survive for extended periods in the environment, facilitating their transmission between individuals. The study identified that spore-forming bacteria are more diverse than non-spore-forming bacteria and that their relative abundance can vary over time. These findings suggest that spore-forming bacteria play a significant role in the heritability of the human microbiota. The study's approach enabled the large-scale culturing, archiving, and genome sequencing of previously unculturable bacteria, providing new insights into the functional attributes of the human microbiota. The results challenge the notion that the majority of the intestinal microbiota is unculturable and highlight the importance of spore formation in the transmission and persistence of intestinal bacteria. The study also identified a genomic signature associated with spore formation, which can be used to predict the sporulation capabilities of bacterial species from diverse environments. This signature includes 66 conserved genes linked to an ethanol-resistance phenotype, which allows for the accurate prediction of sporulation capabilities. The findings have important implications for understanding the transmission and inheritance of the human microbiota.