A variety of causes for infant colic have been suggested, including abnormal gastrointestinal function, immaturity of the gut, spastic colon, accumulation of gas, allergic problems and lack of sufficient parent-to-child interaction. Despite this unclear and possibly multifactorial etiology, studies by independent research groups have correlated alterations in gut microflora with infant colic. This consideration has been growing in importance since the early observations of lower counts of intestinal lactobacilli and bifidobacteria in colicky infants compared to healthy ones. In contrast, evidence suggests that a high proportion of Bifidobacterium and Lactobacillus in the infant’s microbiota is protective against colicky crying and fussing. This protective effect might be related with the fact that mucosal Lactobacillus are able to induce the expression of antiinflammatory genes, improving gut function and motility and exerting a reduction of visceral pain. In addition, lactobacilli and bifidobacteria may protect against colic by modulating immune response.