Antibiotic exposure during first six years of life disrupts gut microbiota and impairs child growth

Newborns subjected to antibiotic therapy reportedly exhibit an altered gut microbiota composition. However, the clinical or microbiological long-term consequences of this exposure remain unknown. Given the causal links between the intestinal microbiota and growth, obesity, and metabolic disease, researchers have suggested that neonatal antibiotic exposure might exert a long-lasting effect on childhood growth by disrupting the natural gut microbiota colonization process.

Altered development...

A study on 12,422 children born from singleton pregnancies at full term provided a host of information. The infants studied had no known growth abnormalities and did not require long-term prophylactic antibiotic treatment. 9.3% of the neonates in the study were exposed to antibiotics (sidenote: Combination of intravenous benzylpenicillin and gentamicin for most infants )  within the first 14 days of life. Among exposed newborns, only boys had significantly lower weights compared to non-exposed children throughout the first six years of life. They also exhibited a significantly lower height and body mass index (BMI) between the ages of 2 and 6 years. This result was confirmed in a German cohort of 1,707 children followed from birth to 5 years. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with a significantly higher BMI in both boys and girls.

...and a modified gut microbiota

To study the effect of neonatal antibiotic exposure on the gut microbiota, fecal samples were collected at the ages of 1, 6, 12, and 24 months from a separate group of 33 newborns, 13 of whom received intravenous benzylpenicillin and gentamicin within the first 48 hours of life. Twenty healthy newborns not exposed to antibiotics in the neonatal period were chosen as controls. The fecal microbiota was analyzed via 16S rRNA gene sequencing. Significant differences between the gut microbiota composition of the antibiotic-treated and control groups were observed after 1 and 6 months, demonstrating the persistence of the effect of antibiotic exposure on the microbiota. The genus Bifidobacterium was most substantially affected, with its content significantly reduced up to 24 months after antibiotic exposure.

Gut dysbiosis in question?

To establish whether causal relationships exist between neonatal antibiotic exposure, gut dysbiosis and child growth, the researchers conducted a complementary study in germ-free mice (sidenote: Germ-free mice mice that have no microbes at all, raised in sterile conditions. ) . The mice received a fecal microbiota transplant (FMT) with feces obtained from antibiotic-exposed children 1 month and 2 years after the antibiotic treatment. A significant reduction in weight gain was observed in male mice that received FMT from antibiotic-exposed infants, as compared to male mice that received FMT from non-exposed infants. In contrast, growth in female mice was not affected.

These findings suggest a causal link between exposure to antibiotics during the first six years of life and growth disorders during childhood which could be caused by the gut dysbiosis that appears during the development of the gut microbiota.