Cross-talk with the microbiota helps the neonatal oral mucosa to mature

The interaction between newborns’ epithelia and the microbiota is crucial to the balance of the oral mucosa and it can have long-term health consequences.
Share on facebook
Share on twitter
Share on linkedin
Share on telegram
Share on whatsapp
Share on email

• Early changes
• Microbial cross-talk

What is already known on this topic
The interaction between newborns’ epithelia and the microbiota can have long-term health consequences. The gut epithelium is known to be important for the early host-microbiota cross-talk, but the role of the mouth epithelium is poorly understood.

What this research adds
Working in mice, researchers studied the oral epithelium and its interactions with the microbiota. Unlike the gut, the oral cavity of newborn mice is home to high levels of microbes, which decline during weaning. Specific immune cells called neutrophils are already present in the oral epithelium before birth, and exposure to the microbiota after birth further recruits them to the mouth. These neutrophils disappear during weaning, when microbial levels in the mouth decrease as a result of increased antimicrobial molecules production in the saliva.

Conclusion

The findings show that the interaction between the microbiota and the oral epithelium after birth is crucial to the balance of the oral mucosa. Studying such cross-talk mechanisms could help to understand how oral illness arise when this maturation process goes awry.

The interaction between newborns’ epithelia and the microbiota can have long-term health consequences. Now, researchers have found that — immediately after birth — the cross-talk between the microbiota and the mouth epithelium is crucial to the balance of the oral mucosa.

The findings, published in Cell Host & Microbe, could help to understand how oral illness arise when the early interaction between the microbiota and the oral epithelium goes awry, the researchers say.

The gut epithelium is known to be important for the early host-microbiota interactions, but the role of the mouth epithelium is poorly understood. To address this question, Hovav Avi-Hai and his colleagues at the Hebrew University of Jerusalem set out to characterize the oral microbiota of laboratory mice from birth to adulthood.

Early changes

In 1-week-old mice, the most common oral bacteria belong mostly to the Pasteurellaceae family, followed by the Streptococcaceae family. During the third and fourth weeks of life, which correspond to the weaning period, the oral microbiota changes, with the Streptococcaceae outgrowing the Pasteurellaceae. During this period, the bacteria present in the mice’s oral cavity become more diversified. Finally, in adult mice, the microbial load decreases substantially and the microbiota returns to a composition more similar to that observed in 1-week-old mice.

The researchers found that specific immune cells called neutrophils are already present in the oral epithelium before birth, and exposure to the microbiota after birth further recruits them to the mouth. That’s because another type of immune cells, which produce a class of inflammatory molecules that attract neutrophils, increased during weaning and then declined to steady-state levels in 8-week-old mice.

Further experiments showed that the mouth epithelium of mice gradually thickens after birth and starts to show adult features during the weaning period, becoming less permeable to microorganisms and their products. This process is impaired in mice born and grown in the absence of microbes, which suggests that the microbiota is required for the efficient closure of the mouth epithelium.

Microbial cross-talk

By the fourth to eighth week of life, the oral epithelium of mice is substantially different from that of newborn mice, the researchers found. In particular, the neutrophils present at high levels after birth virtually disappear during weaning. During this period, microbial levels in the mouth decrease as a result of increased production of saliva and salivary antimicrobial molecules.

Compared to the adult epithelium, the neonatal epithelium has a slower turnover rate and it expresses different levels of specific genes, including those involved in the recognition of microbes and in the production of antimicrobial molecules, the researchers found. What’s more, the colonization of the oral epithelium by the microbiota after birth appears to be important for the upregulation of specific immunological pathways, including those involved in immunity against viral infections, as well as various cellular processes such as cell cycle, growth, and metabolism.

Understanding the mechanisms of interaction between the microbiota and the oral epithelium after birth is important for human health, the researchers say, “because a deficiency of this maturation process could translate into oral and systemic pathologies in adult life.”