By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: Breastfeeding is associated with less frequent bacterial infections and with less subsequent obesity. Using antibiotics reduces or removes these favorable effects of breastfeeding, perhaps via alterations in the intestinal microbiota.

SOURCE: Korpela K, Salonen A, Virta LJ, et al. Association of early-life antibiotic use and protective effects of breastfeeding: Role of the intestinal microbiota. JAMA Pediatr 2016;170:750-757.

The exact mechanisms by which breastfeeding reduces the frequency of infection and the risk of obesity are unknown. However, it is known that breastfeeding affects patterns of intestinal bacterial flora, and that microbiome patterns relate to risks of infection and obesity. Finnish investigators explored the links between early antibiotic use, breastfeeding, and intestinal microbiota.

The study cohort included 226 children, 142 of whom provided stool samples for microbiota analysis. Study subjects were generally healthy, attended day care, and resided in the same region of northern Finland.

The mean duration of breastfeeding was eight (range 0-18) months. By ages 1 and 2 years, respectively, 57% and 88% of children had received at least one course of antibiotic treatment. Half of children received antibiotics before weaning; the other half did not.

Breastfeeding was associated with a marked reduction in bacterial infections (as seen by the proxy of antibiotic use). Each month of breastfeeding related to a 6% reduction of antibiotic use during the first year of life. However, using antibiotics once reduced the effect of breastfeeding on subsequently reduced infections to just 4% per month. A favorable effect of breastfeeding on subsequent antibiotic use persisted, even after weaning.

Similarly, each month of breastfeeding was associated with a 0.08 unit reduction in BMI z score. However, this reduction was not seen in breastfed babies who received antibiotics.

Differences in microbiota composition in the 42 children who underwent full analysis were mainly driven by early antibiotic use and the duration of breastfeeding. Short duration breastfeeding and early antibiotic use similarly altered stool flora toward fewer bifidobacteria and more Clostridia. Early antibiotic use partially negated the otherwise favorable effects of breastfeeding on intestinal microbiota and, thus, on subsequent infections and obesity.

COMMENTARY

In 2014, Infectious Disease Alert reviewed evidence that use of antibiotics during infancy increases the risk of childhood obesity.1 These new data reinforce this idea and provide further understanding of a potential mechanism for the interaction. As elaborated in an editorial accompanying the Finnish paper, the intestinal microbiota composition regulates host metabolic status by producing short-chain fatty acids that then influence the secretion of various peptides that regulate motility, absorption, and satiety. Altering the intestinal microbiota can disrupt small bowel integrity and function in ways that translocate lipopolysaccharides (endotoxins) and trigger low-grade inflammation as is seen in chronic obesity.2

Bifidobacteria are present in human milk, and the predominance of these organisms in infant intestinal microbiota is associated with breastfeeding.3 These bacteria are less common in microbiota of pre-term babies and in babies delivered by cesarean section, perhaps explaining some of the increase in infection in these populations.3

Antibiotic use, either by the laboring mother3 or the baby, is associated with alterations in intestinal flora. These alterations, downgrading bifidobacteria and upgrading clostridial species, are associated with increases in subsequent bacterial infections. Clearly, antibiotics (especially broad-spectrum antibiotics) should be used judiciously.2 Further research is needed to see if the use of probiotics or supplementation of omega-3 fatty acids (as found in breastmilk) can maintain or restore the virginal intestinal microbiota.2

There are several factors that influence intestinal flora and the subsequent risk of infection (and even allergy and obesity).4 It has been suggested that rather than focusing on over-cleaning based on the “hygiene hypothesis,” we should advocate a combination of strategies to help restore the microbiome: natural childbirth, breastfeeding, social exposure through outdoor activities, diet, and appropriate antibiotic use.4 For those of us dealing with potentially infected children, these new data and discussions serve as yet another call to be judicious about our use of antibiotics in infants. 

REFERENCES

  1. Fischer PR, Bhatia R. Broad spectrum antibiotic use in infancy sets table for early childhood obesity. Infectious Disease Alert 2014;34:13-14.
  2. Paolella G, Vajro P. Childhood obesity, breastfeeding, intestinal microbiota, and early exposure to antibiotics — what is the link? JAMA Pediatr 2016;170:735-737.
  3. Lemas DJ, Yee S, Cacho N, et al. Exploring the contribution of maternal antibiotics and breastfeeding to development of the infant microbiome and pediatric obesity. Sem Fetal Neonatal Med 2016;in press. doi 10.1016/j.siny.2016.04.013.
  4. Bloomfield SF, Rook GA, Scott EA, et al. Time to abandon the hygiene hypothesis: New perspectives on allergic disease, the human microbiome, infectious disease prevention and the role of targeted hygiene. Perspect Public Health 2016;136:213-224.