Milk-linked Microbe Mitigates Effect of Antibiotics on Asthma Risk

Written by: Jyoti Madhusoodanan | SPLASH! Issue # 113 | 2023

Asthma, which affects 14% of children and their families around the world [1], is the most common chronic disease of childhood. Several studies have linked an early exposure to antibiotics to an increased risk of asthma [2].

In 2020, a microbiologist from the University of British Columbia, Charisse Petersen, and her colleagues reported that decreasing the use of antibiotics was correlated with lower rates of asthma, and the effect was likely because of a healthier gut microbial community [3]. Although reducing antibiotic use is important, it’s not an option for all children. “We can’t eliminate antibiotics,” Petersen said in an interview. “Some babies really need these medications.”

An effort to understand how to help these children led the researchers to investigate the links between breastfeeding and asthma. Thus far, the evidence has been murky: some studies suggested breastfeeding had a protective effect and reduced the risk of asthma, whereas others found no benefit. The confusion stems, in part, from the immense variability in the composition of breastmilk, antibiotic dosing, and other environmental exposures that can trigger asthma.

In a new study, the team turned to data from the CHILD cohort study, a project that observes the health of children from mid-pregnancy until adolescence [4]. For the current work [5], Petersen and her colleagues included 2,521 children from the larger cohort, 2,102 of whom received no antibiotics in the first year of life, 286 received systemic antibiotics while breastfeeding, and 133 received antibiotics but were not breastfed. The team found that compared with children who received no antibiotics, those who received the medicines without breastfeeding were three times more at risk of developing asthma by age five. “But if kids were being breastfed by when they received those antibiotics, this risk almost went away,” Petersen said. “We found that breastfeeding itself might be one of the most beneficial things if a child needs antibiotics in the first year of life.”

But the researchers did not just stop there. Knowing that not all children can be breastfed and there can be significant variations in the chemistry of milk that could contribute to the positive effect of breastfeeding on asthma development, Petersen and colleagues continued on to characterize why breastmilk appeared to be protective.

The team sequenced the gut microbiome of 1,338 children from samples collected in early infancy (~3 months) and at about 1 year of age to characterize microbial changes. Compared with children who received no antibiotics, those who received them but did not breastfeed had significantly lower diversity of their gut bacteria. But this decrease was absent in those who were also breastfed when receiving the medicines. Since the developing gut microbiome is sensitive to nutrients, drugs and other external forces, antibiotics can cause significant perturbations, Peterson explained. “Breastfeeding seemed to counteract some of the imbalance that the antibiotic was causing,” she added.

To confirm whether the positive effect of breastfeeding on asthma development was a result of the components of milk or because of maternal milk’s effects on gut microbes, the team compared the genetic diversity of bacterial strains across the samples. They found that breastfeeding was linked to an increase in the abundance of a species named Bifidobacterium longum. Comparing three subspecies, they narrowed the benefits down to one subspecies, B. longum infantis. The authors write in their paper that “B. infantis may act as a keystone species to buffer the effects of antibiotics on the functional infant.”

The subspecies B.infantis thrives on human milk, so the authors examined whether specific components of milk could boost levels of this bacteria. “It was very important for us to find a way to afford this same protection for kids who can’t be breastfed but still need antibiotics,” Peterson said.

The investigators found that some of the breastmilk fatty acids, such as linoleic acid and arachidonic acid, were negatively correlated with the abundance of the subspecies B. infantis in the infant gut. But many human milk oligosaccharides (HMOs) correlated with higher levels of B. infantis, suggesting that “these HMOs may increase B. infantis colonization and maintain functional diversity in the microbiome in children receiving antibiotics,” the authors wrote in the study. Although more research is needed, these data could eventually inform ways in which HMOs and B. infantis can be used together to reduce the risk of asthma in children who need antibiotics. “A hope of our study is to inform research that is moving in that direction, Peterson said.

References

1. Pearce N, Aït-Khaled N, Beasley R, Mallol J, Keil U, Mitchell E, Robertson C. Worldwide trends in the prevalence of asthma symptoms: phase III of the International Study of Asthma and Allergies in Childhood (ISAAC). Thorax. 2007 Sep 1;62(9):758-66.
2. Ni J, Friedman H, Boyd BC, McGurn A, Babinski P, Markossian T, Dugas LR. Early antibiotic exposure and development of asthma and allergic rhinitis in childhood. BMC Pediatrics. 2019 Dec;19(1):1-8.
3. Patrick DM, Sbihi H, Dai DL, Al Mamun A, Rasali D, Rose C, Marra F, Boutin RC, Petersen C, Stiemsma LT, Winsor GL. Decreasing antibiotic use, the gut microbiota, and asthma incidence in children: evidence from population-based and prospective cohort studies. The Lancet Respiratory Medicine. 2020 Nov 1;8(11):1094-105.
4. Subbarao P, Anand SS, Becker AB, Befus AD, Brauer M, Brook JR, Denburg JA, HayGlass KT, Kobor MS, Kollmann TR, Kozyrskyj AL. The Canadian Healthy Infant Longitudinal Development (CHILD) Study: examining developmental origins of allergy and asthma. Thorax. 2015 Oct 1;70(10):998-1000.
5. Dai DL, Petersen C, Hoskinson C, Del Bel KL, Becker AB, Moraes TJ, Mandhane PJ, Finlay BB, Simons E, Kozyrskyj AL, Patrick DM. Breastfeeding enrichment of B. longum subsp. infantis mitigates the effect of antibiotics on the microbiota and childhood asthma risk. Clinical Advances. 2023 4(2): 92-112.

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