There is considerable agreement that the gastrointestinal microbiota contributes to the performance and health of the neonate, and this relationship includes an ability of the host animal to “sense” changes in the microbial community. Identifying the mechanisms used by the host to sense microbiota is one approach to developing methods to manipulate the microbiota to improve pig health and performance. Diet-independent microbial products are molecules unique to the microbial community and sensed by host pattern recognition receptors stimulating inflammation. Common among all members of the microbial community, their presence is unaffected by diet, but the nature of the response does depends on factors affecting the microenvironment in which the molecule is detected. Diet-dependent microbial products arise as products of fermentation of dietary components and include short-chain fatty acids, ammonia, phenols, hydrogen sulfide, amines, and many other compounds. A plethora of sensing mechanisms exists that include enzymatic metabolism as well as membrane receptors that have evolved to respond to microbial products (e.g., short-chain fatty acid receptors), or simply cross-react with microbial products. This review focuses on host mechanisms used to sense the intestinal microbiota and attempts to establish practical considerations for neonatal gut health based on current understanding.