Meningitis is associated with high mortality and often causes severe sequelae. Newborns are particularly susceptible to this type of infection; they are 30 times more likely to develop meningitis than the general population. Group B streptococci (GBS) are the most common cause of neonatal meningitis, but they are rarely responsible for the disease in adults. Scientists from the Pasteur Institute, in collaboration with Inserm, Université de Paris and Necker-Enfants Malades Hospital (AP-HP), have tried to explain the susceptibility of newborns to GBS meningitis. In a mouse model, they showed that the immaturity of both the gut microbiota and epithelial barriers such as the gut and choroid plexus play a role in the susceptibility of newborns to bacterial meningitis caused by GBS. The results were published in the journal Cell Reports on June 29, 2021.
Newborns are more likely to develop bacterial meningitis than children and adults. Group B streptococci (GBS) are the pathogen responsible for a significant proportion of cases of neonatal meningitis. In most cases, the infection is preceded by bacterial colonization of the intestine. The commensal bacterial intestinal flora (so-called microbiota) plays an important physiological role as it is involved in digestion, offers protection against intestinal pathogens and contributes to tissue differentiation and immune development. Newborns have no gut microbiota; it develops gradually in the first few weeks after giving birth.
In a new study, scientists from the Pasteur Institute in collaboration with Inserm, Université de Paris and Necker-Enfants malades Hospital (AP-HP) have shown in a mouse model that the immaturity of the intestinal microbiota in newborns is involved in the susceptibility of newborns to one through GBS caused meningitis. In the absence of a mature microbiota, the bacteria can colonize the intestine over a large area. In the absence of a mature microbiota, the barrier function of the blood vessels in the intestine, which bacteria must cross to get to the brain via the bloodstream, is also less effective and the immune system is unable to control infections.
Unexpectedly, the scientists also showed that regardless of the microbiota, the epithelial barriers formed by the gut and choroid plexus (the interface between blood and the cerebrospinal fluid that flushes the brain) are not fully developed in newborns, making it easier for bacteria to access to the brain. The signaling pathway known as the Wnt pathway, which is involved in tissue growth and differentiation, is more active in newborns, which leads to a less effective barrier function at the intestinal and choroidal plexus level in newborns.
“In this study, we show how two factors in infancy – the immaturity of the gut microbiota and the growth of intestinal and choroidal epithelial tissue – play a role in the susceptibility of newborns to GBS-related meningitis at all stages of infection.” until it spreads in the brain, ”explains Marc Lecuit (university professor / clinician, Université de Paris and Necker-Enfants Malades Hospital), head of the department for infection biology at the Pasteur and Inserm Institute and last author of the study.
The results of this research illustrate the importance of the microbiota and its critical role in protecting against infection.