Gut microbiome changes precede eczema development in infancy

Key takeaways:

• Infants with eczema had enriched Clostridium sensu stricto 1 and Finegoldia and depleted Bacteroides.
• The biggest changes in the gut microbiome occurred between ages 6 and 12 months.

Changes in the gut microbiota of infants preceded the development of eczema, according to a study published in mSystems.

Interventions that target key bacteria may prevent or mitigate later eczema, Paul Chan, MD, professor of microbiology at The Chinese University of Hong Kong, and colleagues wrote.

“The problem of eczema is increasing, and our study shows it could be a result of unwanted changes in the gut bacterial content,” Chan said in a press release. “The first year of life could be a critical period to restore the gut bacteria to a more desirable composition.”

The Stool Microbiome and Allergic ReacTion (SMART) Baby Study used 16S rRNA gene sequencing to characterize the gut microbiome of 112 children (50.9% boys) in China born at term from birth through age 3 years. The cohort included 85 (75.9%) born vaginally, with a mean gestational age at birth of 39.3 weeks and mean maternal age of 32.5 years.

Also, 57 of the mothers (50.9%) had received intrapartum antibiotics, and 24 infants (21.4%) had been exclusively breastfed through age 6 months, with 64 infants (57.1%) consuming solid food before age 6 months.

At age 6 months, 48 infants (42.9%) had physician-diagnosed eczema. At age 12 months, 34 infants (30.4%) had physician-diagnosed eczema. Mean age of onset was 2.7 months. More than 70% of these cases were mild or moderate.

Differences in microbiota

The researchers collected 713 stool samples at nine time points between birth and age 3 years, over which time the researchers found gradual increases in the richness and Shannon diversity of the gut microbiota.

The researchers noted the biggest changes between age 6 and 12 months, with enrichment of the genera (Ruminococcus) gnavus group, Blautia and Faecalibacterium and depletion among Bifidobacterium, Escherichia-Shigella and Enterococcus. Several amplicon sequence variants (ASVs) changed as well.

During the first month of life, the main determinant of the gut microbiota was mode of delivery, followed by intrapartum antibiotics use. The effect size of these variables fell through age 12 months, with feeding mode surpassing them at age 6 months.

Compared with infants born via cesarean section, infants born vaginally had gut microbiota that were significantly enriched with Bacteroides and Parabacteroides through age 6 months.

The microbiota of infants born via cesarean section were significantly enriched with Clostridium sensu stricto 1 and Enterobacter at ages 1 and 3 months, Enterococcus and Veillonella at age 1 month and Klebsiella at ages 3 and 6 months.

Infants who were exclusively breastfed had microbiota enriched with Haemophilus and Staphylococcus at ages 3 and 6 months and with Limosilactobacillus, Bifidobacterium, Veillonella, Streptococcus, Lacticaseibacillus and Megasphaera at age 12 months.

The microbiota of infants who were exclusively fed formula were enriched with Intestinbacter at ages 3 and 6 months, Ruminococcaceae incertae sedis at age 6 months and Flavonifractor at age 12 months.

Infants of mothers who received intrapartum antibiotics during labor had microbiota enriched with an unclassified genus of Enterobacteriaceae at age 1 month and depleted Eubacterium at age 12 months.

Associations with eczema

Next, the researchers analyzed 188 stool samples collected at ages 1, 3, 6 and 12 months from 23 infants who had physician-diagnosed eczema at age 12 months and from 24 infants who did not have any eczema through age 12 months.

The researchers found no significant differences in gut microbiota alpha or beta diversity between the eczema and control groups at any time points.

However, the eczema group had enriched Clostridium sensu stricto 1 at age 3 months (P < .01) and depleted Bacteroides at all four time points (P < .05), in addition to other differentially abundant genera, according to the researchers.

The control group had a mean relative abundance of Bacteroides that was higher than the full cohort’s global mean between age 1 and 6 months, whereas the eczema group had lower mean relative abundance of Bacteroides compared with the global mean at age 1, 3 and 12 months.

The eczema and control cases both had lower mean relative abundance of Clostridium sensu stricto 1 compared with the global mean through age 6 months. Both groups also had differences in mean relative abundance as early as age 1 month, although these differences were not statistically significant, nor did they persist, according to the researchers.

The eczema cases also had an enriched Clostridium sensu stricto 1 ASV between age 1 and 6 months (P < .05). At age 12 months, eczema severity based on objective Scoring Atopic Dermatitis (oSCORAD) scores had a negative correlation with Shannon diversity (rho = –0.57; P = .017).

There also were positive correlations between relative abundance of Clostridium sensu stricto 1 at age 3 months and SCORAD (rho = 0.61; P = .016) and oSCORAD (rho = 0.62; P = .013) scores at age 6 months. Also at age 6 months, there was a trend for the relative abundance of Bacteroides to correlate negatively with the oSCORAD score (rho = –0.48; P = .068).

Similarly, another subset of 189 stool samples from 33 infants with physician-diagnosed eczema and 30 infants who never had any eczema collected at ages 1, 3 and 6 months did not exhibit any differences in alpha or beta gut diversity except for higher Shannon diversity among the infants with eczema at age 6 months (P < .05).

The eczema group also had enriched Clostridium sensu stricto 1 at 3 months. The eczema and control groups had similar mean relative abundances of this genus, the researchers said, and these abundances were lower than the global mean at age 1 month. However, this abundance remained high in the eczema group at age 3 months but decreased along with the global pattern in the control group.

Conclusions, next steps

Overall, the researchers found that alpha diversity increased and beta diversity changed in the gut microbiome through age 3 years, preceding the development of eczema. These bacteria may indicate potential microbial markers for early prognosis or diagnosis of eczema, they continued.

“Our study found that the gut bacterial content of babies changes drastically over the first 3 years of life. The mode of delivery and feeding, and the use of antibiotics around the time of delivery, affects the gut bacterial content,” Chan said in the press release.

“We observed characteristic changes in the gut bacterial content before the babies present with eczema,” he continued. “Remarkably, those bacterial changes were also observed in babies delivered by c-section. Nevertheless, the link between c-section and eczema requires further studies to verify. Gut bacteria may play a role in preventing or treating eczema.”

Additional studies with animal models may confirm the role that these taxa play in the development of eczema, the researchers wrote. Interventions that modulate the abundance of these bacteria during the first few months of age may prevent the onset or attenuate the severity of later eczema, they concluded.

Reference:

• Study reveals important associations between gut microbiome and eczema in infancy. https://asm.org/Press-Releases/2023/August/Study-Reveals-Important-Associations-Between-Gut-M. Published Aug. 30, 2023. Accessed Aug. 30, 2023.