Neonates are highly susceptible to intestinal infections; this has been generally ascribed to the immaturity of the immune system, but other factors might contribute. Kim, Sakamoto et al. show that the composition of the gut microbiota is a key factor, as the microbiota protects the host against colonization by pathogens. The neonatal gut microbiota is less diverse and lacks two taxa that are dominant in older intestines: members of the orders Clostridiales and Bacteroidales. Administration of members of the Clostridiales, but not Bacteroidales, protected germ-free adult mice that were colonized with neonatal microbiota from infections, whereas in absence of members of the Clostridiales, both adults and neonates became susceptible. Importantly, host immunity did not contribute to the clostridia-mediated effect. The authors hypothesize that oxygen consumption by aerobic or facultative anaerobic bacteria in the gut could promote colonization by strict anaerobes, such as Clostridiales, which, in turn, could grant protection from enteric pathogens during the first days of life.