Babies born during lockdown had different microbiomes, impacting allergic disease
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Key takeaways:
- These babies had more Bifidobacteria and less Clostridia.
- Prevalence of atopic dermatitis was lower than expected.
- Food and aeroallergen sensitizations were within previous ranges.
Babies born during the lockdown of March through May 2020 developed significant differences in their microbiome and less atopic dermatitis compared with babies born prior to this period, according to a study published in Allergy.
This environment also led to lower infection rates with less antibiotic use as well as prolonged breastfeeding, Katri Korpela, PhD, associate professor, human microbiome research program, faculty of medicine, University of Helsinki, and colleagues wrote.
The Impact of Corona Virus Pandemic on Allergic and Autoimmune Dysregulation in Infants Born During Lockdown (CORAL) study included 360 infants (55% boys; 96% white) born between March and May 2020. Also, 46% of these infants were the first born in their families, and 65% were born via spontaneous vaginal delivery.
The 4.7% of infants with a detectable antibody response to SARS-CoV-2 at age 12 months indicates the effectiveness of social distancing in minimizing exposure, the researchers said. So did the 17% who required antibiotics by age 12 months, compared with 80% requiring antibiotics in a pre-pandemic birth cohort, the researchers continued.
These infants also had medians of one in-person social contact outside the home at birth and four such contacts at age 6 months. Additionally, 25% of these infants had not met a child their own age before their first birthday.
The cohort’s microbiota
The researchers collected fecal samples from 351 infants at age 6 months and from 343 infants at age 12 months. Firmicutes, Bacteroidetes and Clostridia increased and Actinobacteria and Proteobacteria decreased in relative abundance with age.
Also, the researchers said cesarean delivery was associated with increased greater relative abundance of Firmicutes and Protobacteria and decreased relative abundance of Actinobacteria and Bacteroidetes at 6 months. Similar trends were found in vaginal birth with intrapartum antibiotic exposure.
The researchers additionally found associations between antibiotic exposure by 6 months and reduced relative abundance of Bifidobacterium breve, Clostridium neonatale and Veillonella and increased relative abundance of Bacteroides ovatus, Ruminococcus gauvreauii and Klebisella pneumoniae.
Diet was the primary driver of microbiota composition, the researchers continued, with significant positive and negative associations between breastfeeding and multiple taxa at both 6 and 12 months.
Diets including oil, beans and nuts resembled breastfeeding as they directed microbiota toward increased relative abundances of Bifidobacterium, Lactobacillus, Collinsella and Bacteroides, the researchers said. Cow’s milk and other animal-derived products moved the microbiota away from composition dominated by Bifidobacterium and Bacteroides.
Variance in microbial composition due to exposure to siblings grew from 1% at age 6 months to 9% at age 12 months. Also, pets accounted for 3% of the microbiota at age 6 months. Exposure to other children, rural vs. urban living environments, and environments outside the home such as daycare became significant by age 12 months.
Increases in the relative abundance of Clostridia were driven by pets at age 6 months and by siblings, daycare attendance and rural environments at age 12 months, representing the major driver of differences in microbiota at those ages.
Comparisons with pre-lockdown cohorts
Next, the researchers compared these profiles against data from 34 prior studies involving 3,825 infants and 5,732 fecal samples. The microbiota of the infants in CORAL had similar time-dependent abundances of Bacilli, Proteobacteria and Bacteroidia, compared with the earlier cohorts.
Levels of Clostridia were significantly lower in the CORAL cohort at ages 6 and 12 months (P < .001), the researchers said. The CORAL cohort also had an elevated relative abundance of Bifidobacterium (class Actinomycetia) at age 12 months (P < .0001).
Compared specifically with the INFANTMET cohort, CORAL had significantly less abundant Clostridia at ages 6 months and 12 months and significantly more bifidobacteria (P < .0001 for all), the researchers said.
Further, CORAL had greater microbial richness at age 6 months, but this pattern had reversed by age 12 months because this richness increased at a lower rate in the CORAL cohort, the researchers continued.
The researchers additionally created an exposure index including family members who were classified as essential workers, numbers of siblings, numbers of adults in the household, daycare attendance and pets.
After adjusting for birth mode and breastfeeding, the researchers said there was an association between the relative abundance of Clostridia in the CORAL cohort and the exposure index (P = .039) at age 6 months.
The trend between all Clostridial genera and the exposure index was positive with statistical significance (P < .05) for 27 of the 39 (69%) genera. There was a significant negative association between the exposure index and the relative abundance of Bifidobacterium as well (P < .0001).
Also, there was a positive association between the exposure index and microbial richness at age 6 months (P = .01) but not between the exposure index and Clostridia or richness at age 12 months.
Daycare attendance and babysitters who were not among the infant’s parents, which the researchers said were arguably the most important sources for exposures to microbes from outside the home, were associated with Clostridia at age 12 months (P = .029).
There was no association between breastfeeding and the exposure index at age 6 months, but there was an association between breastfeeding and lower exposure index values at age 12 months (P = .03).
Allergic diseases
Based on data from previous studies of AD in children in Europe, the researchers predicted that the prevalence of AD among children would be 26.8% in 2021.
The researchers diagnosed 87 infants (24.8%) in the CORAL cohort with atopic dermatitis at age 12 months, with a median Scoring Atopic Dermatitis (SCORAD) score of 10.1, and 68 children (19.5%) in the cohort with AD at age 24 months, with a median SCORAD score of 7.9.
Both rates were lower than the predicted prevalence and were within recently reported ranges for Europe, the researchers said.
Additionally, prevalence of AD as defined by UK Working Party criteria included 16% of those infants cared for by someone who was not their parent (n = 191) and 8% among those with maximal social isolation (n = 141) at age 12 months (P = .022).
Food allergen sensitization levels, determined by skin prick testing, included 6.7% at age 12 months and 4.5% at age 24 months. Aeroallergen sensitization levels, also determined by SPT, included 1.5% at age 12 months and 8.9% at age 24 months.
The researchers said that the food allergen sensitization levels also were within recently reported ranges for Europe and that that the aeroallergen sensitization was low, which is typical for this age group as well.
The prevalence of IgE-mediated food allergy included 4.7% at age 12 months and 1.7% at age 24 months. Additionally, the prevalence of non-IgE food reactions included 7.8% at age 12 months and 2.2% at age 24 months.
Specifically, the researchers noted negative associations between AD and SPT positivity and bifidobacterial levels at age 6 months and relative abundance of butyrate producers at age 12 months.
Conclusions, next steps
Considering the differences in gut microbiota between infants born before and during the lockdown, the researchers said they found associations between specific taxa and risk for allergic diseases.
Also, they said, the lack of an increase in the prevalence of allergen sensitization, food allergy or AD compared with pre-pandemic levels indicate that increases in the relative abundance of beneficial, maternally transmitted microbes and in plant-based dietary supports may protect infants against allergic diseases.
Conversely, the researchers continued, factors such as cesarean birth, a lack of breastfeeding and frequent antibiotic use may contribute to increases in the prevalence of allergic diseases.
The researchers said they hope to re-examine these children at age 5 years to examine the longer-term impacts that these changes in the gut microbiome may have on them.
Reference:
- New APC research reveals that lockdowns had an impact on gut microbes and allergies in newborns. https://www.ucc.ie/en/apc/news/apc-news/new-apc-research-reveals-that-lockdowns-had-an-impact-on-gut-microbes-and-allergies-in-newborns.html. Published Feb. 29, 2024. Accessed March 22, 2024.
Perspective
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This is a really interesting study. Kudos to the investigators, as it took a terrible situation (the pandemic and social distancing measures) and used it to further knowledge about the effects of relative social isolation on the microbiome and atopic diseases.
My expectation would have been to see decreased microbial diversity after the distancing, with a subsequent increase in atopic diseases. But they did not find this, so I do think it is a bit surprising.
I think this will help us better understand the relative impact of the environment on the microbiome. It suggests that breastfeeding, plant-based foods, siblings, rural environments, pets and smoking in the home have powerful impacts on the microbiome, presumably greater than socialization, at least when it comes to this particular set of outcomes. Diet especially stood out as the most dominant factor for gut microbiota, which is really striking, though not too surprising, I suppose.
As a clinician seeing lots of eczema patients and their families, it is often frustrating because people want to know the “root cause” that is driving these conditions. We have seen a huge increase in the number of patients with eczema and food allergies in the past decades, and this is far too rapid to be attributed to genetics. Clearly there is something environmental, in the largest sense, that explains this.
Diet has changed dramatically in the past few generations, to the point that books and articles about diet now must differentiate between “food” and “food-like substances,” ie, highly processed foods. We also understand that additives such as emulsifiers and preservatives are very likely having an impact on the microbiome as well as on overall health.
So, how can doctors use these findings to improve care? That is the multi-billion-dollar, translational question! I do not think we know yet. We are still, to some degree, stumbling around in the dark when it comes to the microbiome. I do not think we even yet have the tools to really understand the important interactions between strains of bacteria, let alone fungi and viruses, on the skin.
To me, at least, it seems likely that one day we will chuckle at how crude these analyses were, perhaps akin to trying to count the number of wires in a computer to understand it, failing to see that the wires serve only as connectors to the microchips. But, as with many things, the truth often seems like a platitude, and the authors’ conclusion helps us know the general direction to go: Encourage breastfeeding, be careful stewards of antibiotics, and eat plant-based, unprocessed diets when possible.
I think we need more and deeper understanding of how the microbiome works together. I think this is a big data problem that will require new ways of looking at the interactions between species and how these interactions affect the individual. In the meantime, I think we need more studies like this to help us understand where to look, and this has done a great job of pointing the arrow at particularly important areas.
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