Study of the Week: Undeveloped Microbiota and Epithelial Barriers in Newborns Boost Bacterial Meningitis Risk

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

 

This week’s study is…

Neonatal susceptibility to meningitis results from the immaturity of epithelial barriers and gut microbiota

We previously published about this research in a story titled “New Study Has Demonstrated The Role of The Gut Microbiota in Neonatal Bacterial Meningitis” which can be found here. The study was originally published in the scientific journal Cell Reports. You can view the full text of the study here.

This research team was affiliated with the Institut Pasteur, Inserm, Université de Paris, and Necker-Enfants Malades Hospital.

What Happened?

Neonates (newborns) are known to be at a far greater risk of catching bacterial meningitis; in fact, they develop the disease at 30 times the rate of the overall population. Prior research has also indicated that newborn cases of the disease are predominantly triggered by Group B streptococcus (GBS), a bacterial strain that is almost never responsible for infection in older patients. In infants, the disease is generally the result of colonization of the intestine by GBS via translocation through the intestinal barrier.

In this study, the researchers sought to gain a greater understanding of why newborns are at such a high risk of bacterial meningitis. This study used mice of different ages who were orally inoculated with GBS at different ages. As the mice got older, the diversity of bacteria in their gut changed and increased. The researchers found that older mice saw a greater reduction of bacterial burden in the brain and gut, suggesting that a developed gut microbiota had a protective effect against GBS.

However, other factors were found to be involved as well. Outside of microbiota maturation, younger individuals still appeared more vulnerable. This was linked to Wnt activity in the choroid and intestinal plexus, which was characterized by less cell-cell junction polarization. These conditions favor bacterial translocation. Overall, immaturity of the microbiota and neonatal tissue growth developmental pathways in newborns were determined to be the primary reasons why they are more vulnerable to bacterial meningitis and are susceptible to GBS colonization in particular. 

About Bacterial Meningitis

Bacterial meningitis is a disease in which the protective membranes around the spinal cord and brain, known as the meninges, become inflamed. Because of how close the inflammation is to the spine and brain, meningitis constitutes a medical emergency that must be addressed in a timely fashion. Bacterial meningitis is the result of an infection with a pathogenic bacteria. Characteristic symptoms of the disease include headaches, stiff neck, and an altered state of consciousness. Other symptoms include fever, intolerance of loud noises and light, and vomiting. Without prompt treatment, bacterial meningitis can inflict long-term problems such as cognitive disability, deafness, and epilepsy. Treatment depends on the cause, but if the disease is suspected, antibiotics are recommended as soon as possible, even if the definite diagnosis hasn’t been confirmed. In the Western world, bacterial meningitis is rare. To learn more about meningitis, click here.

Why Does it Matter?

The results of this study demonstrate the decisive role that the gut microbiota can play in human health and how a fully developed and balanced microbiota can be a major contributor to immune system function. While newborns are considered at greater risk of infection due to their less fully developed immune systems, these findings add a new layer of complexity. In addition, it gives the medical community a much clearer and more specific explanation for why newborns are at such an elevated risk of GBS-related bacterial meningitis:

“In this study, we show how two factors associated with infancy—the immaturity of the gut microbiota and the growth of gut and choroidal epithelial tissues—play a role in the susceptibility of newborn infants to meningitis caused by GBS, at all stages of infection from gut colonization to dissemination in the brain.” – Marc Lecuit (university professor/hospital practitioner, Université de Paris and Necker-Enfants Malades Hospital), head of the Biology of Infection Unit at the Institut Pasteur and Inserm, last author

With this greater understanding now at hand, future research can focus on solutions that reduce the risk of bacterial meningitis in newborns or prevent it altogether. Such interventions may include methods that could help the gut microbiota reach a mature state more quickly, therefore reducing the period in which the gut is vulnerable to GBS colonization. This could perhaps be achieved through the use of prebiotics or probiotics. 

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