The inconsolable crying of a child for no apparent reason at an early age is a source of excitement and anxiety for parents. Previous studies have reported that crying may be caused by discomfort associated with the occupation of the intestines of the newborn by microbiota and its vital activity. We conducted a prospective observational study in which 62 newborns and their mothers were recruited. The study comprised two groups, each consisting of 15 infants with colic and 21 controls. Colic and control groups were vaginally born and exclusively breastfed. Fecal samples from children were collected over time from day 1 to 12 months. Full metagenomic sequencing of fecal samples from children and their mothers was carried out. It was determined that the trajectory of the development of the intestinal microbiome of children with colic was different from the group without colic. In the colic group, a depleted relative abundance ofBifidobacteriumand enrichment ofBacteroides Clostridialeswas found, while the microbial biodiversity in this group was enriched. Metabolic pathway profiling showed that the non-colic group was enriched by amino acid biosynthetic pathways, while the feces microbiome of the colic group was enriched by glycolysis metabolic pathways that correlated with theBacteroidestaxon. This study shows that infantile colic has a definite relationship with the microbiome structure of infants.