Modulation of the gut microbiota to improve innate resistance

•Host and microbiota cooperate to maintain a gut ecosystem refractory to pathogen colonization.•Specific bacteria enhance protection via intermicrobial competition or by modulating host metabolism and immunity.•The gut microbiota contributes to colonization resistance at extra-intestinal sites through MAMPS and metabolites.•Diet modulates colonization resistance by influencing microbiota composition and metabolism. One major benefit from the association of hosts with the complex microbial communities that establish at body surfaces is the resistance to pathogen infection. This protective role of symbiotic microbes is becoming ever more relevant, given the alarming rise of multidrug-resistant pathogens and severe infections in patients following extensive antibiotic treatment. Herein, we highlight some recent mechanistic studies that have provided insights into how the highly dynamic dialogue amongst intestinal bacteria and between intestinal bacteria and their host can contribute to protect the host against pathogens in and outside the gut. We then discuss how delineating the rules of this dialogue can help design strategies to modulate the microbiota and improve host resistance to infections.