The microbiota drives defense against nosocomial bacterial pathogens. (A) Enterococcal infections can be deleterious to the antibiotic-treated host, as Enterococci can translocate into the bloodstream. Loss of colonization resistance is an important component in the manifestation of these infections, and colonization resistance is mediated through several mechanisms, including direct inhibition by commensal strains of E. faecalis and obligate anaerobes such as B. producta, Parabacteroides distasonis, Bacteroides sartorii, and C. bolteae. Bacteria-derived TLR ligands drive indirect inhibition by stimulating production of RegIIIγ. (B) C. difficile infection can cause severe colitis by inducing epithelial cell death, and this loss of epithelial integrity allows for residual bacteria remaining after antibiotic treatment to spill into the underlying tissue and bloodstream. Spores of C. difficile are ingested by the host and germinate into vegetative cells upon stimulation by primary bile acids. When the microbiota is unperturbed by antibiotics, bacteria such as C. scindens are present and can convert primary bile acids into secondary bile acids, which inhibit vegetative cell growth. Succinate is a metabolic by-product of commensal bacteria, and sialic acid is a host-derived carbohydrate that is cleaved from epithelial cells by commensals and released into the intestinal lumen. At steady state, succinate and sialic acid support sustained growth of various commensal species, but when antibiotics are administered, the commensal species that would benefit from these factors are eliminated, leaving them to be used by vegetative C. difficile to facilitate its own growth instead. (C) Enterobacteriaceae are a family of bacteria that are adept at exploiting the antibiotic treated intestine by inducing inflammation, a setting in which Enterobacteriaceae can exploit to facilitate their own expansion. Commensal bacteria produce butyrate as a by-product of carbohydrate fermentation, which in turn prevents inflammation and also directly kills Enterobacteriaceae in the presence of acidified pH. Loss of butyrate production reduces PPARγ signaling in epithelial cells, inducing inducible nitric oxide synthase (iNOS) expression that can be used as a substrate for nitrogen respiration in Enterobacteriaceae. This increased availability of iNOS is exploited by Enterobacteriaceae, creating a positive feedback loop that enables expansion of these opportunistic pathogens since the increased presence of Enterobacteriaceae can in turn lead to increased expression of iNOS.