Clostridium perfringens, a rapid-growing pathogen known to secrete an arsenal of >20 virulent toxins, has been associated with intestinal diseases in both animals and humans throughout the past century. Recent advances in genomic analysis and experimental systems make it timely to re-visit this clinically and veterinary important pathogen. This Review will summarise our understanding of the genomics and virulence-linked factors, including antimicrobial potentials and secreted toxins of this gut pathogen, and then its up-to-date clinical epidemiology and biological role in the pathogenesis of several important human and animal-associated intestinal diseases, including pre-term necrotising enterocolitis. Finally, we highlight some of the important unresolved questions in relation to C. perfringens-mediated infections, and implications for future research directions.

Summary Supplementation with members of the early-life microbiota as “probiotics” is increasingly used in attempts to beneficially manipulate the preterm infant gut microbiota. We performed a large observational longitudinal study comprising two preterm groups: 101 infants orally supplemented with Bifidobacterium and Lactobacillus (Bif/Lacto) and 133 infants non-supplemented (control) matched by age, sex, and delivery method. 16S rRNA gene profiling on fecal samples (n = 592) showed a predominance of Bifidobacterium and a lower abundance of pathobionts in the Bif/Lacto group. Metabolomic analysis showed higher fecal acetate and lactate and a lower fecal pH in the Bif/Lacto group compared to the control group. Fecal acetate positively correlated with relative abundance of Bifidobacterium, consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides into acetate. This study demonstrates that microbiota supplementation is associated with a Bifidobacterium -dominated preterm microbiota and gastrointestinal environment more closely resembling that of full-term infants.