Valuable protection: Is the variety of gut bacteria more important than immune system in newborns?
Published in Science journal, the work specifically suggests that Clostridia bacteria could provide significant protection against infection when transplanted to newborn subjects. Additionally, the study confirms that newborns do not have Clostridia in the gut - making them vulnerable to invading bacteria that cause sickness.
The World Health Organization (WHO) identifies one of the major causes of neonatal deaths worldwide are infections (36%, which include sepsis/pneumonia, tetanus and diarrhoea).
“Newborns are very susceptible to infections in the first year of life, including enteric, or gut, infections," explained Dr Gabriel Nunez, lead study author and professor of pathology at the University of Michigan.
"This work suggests that the lack of protective bacteria in the gut microbiota is a mechanism for that susceptibility, perhaps more than the age of the immune system."
The gut microbiota of neonates is less diverse than that of adult individuals and tends to lack Clostridiales and Bacteroidales, the dominant species found in the adult intestine, noted the team.
The work paves the way for new approaches that protect babies from frequent infection by orally acquired bacterial pathogens.
Most of the infection-related deaths could be avoided by treating maternal infections during pregnancy, ensuring a clean birth, care of the umbilical cord and immediate, exclusive breast-feeding.
Germ-free mice subjects
Along with colleagues from the PRESTO, Japan Science and Technology Agency, the team used newborn and adult mice bred with no microorganisms living in or on them (germ-free).
Faecal samples taken from 4-day-old, 12-day-old and 16-day-old normal mice were also analysed for use in the series of experiments.
Samples from the older mice showed a greater microbial diversity with species that included Clostridia and Bacteroides.
In contrast, samples from the younger mice did not contain these species obtaining nutrition from their mother's milk.
Bacterial samples from the 4-day or 16-day-old mice were transplanted to the germ-free mice. These mice were then exposed to a strain of Salmonella that can infect the gut but not spread throughout the body.
Around 50% of the mice that received the 4-day old transplantation died. However, those that received the 16-day old transplantation all survived.
The same procedure was repeated with Citrobacter rodentium - a strain of bacteria that can cause a variety of intestinal infections.
Here, germ-free mice with transplanted 4-day microbes got sick and many died.
However, when the bacteria from 16-day-old normal mice was transplanted, the population of C. rodentium in the gut of surviving mice decreased.
The team then gave germ-free mice that had been given a newborn mouse's microbes, an added dose of either Clostridia or Bacteroides bacteria.
Some of these mice were then exposed to the C. rodentium species. It was found that 90% of the mice that received the Clostridia, then were exposed to Salmonella, were still alive after 7 days.
In contrast only 50% of those that hadn't received the Clostridia dose remained alive.
Host immune system tested
Further experiments looked at the host's own immune system comparing its ability to fight infection against its own gut microbiome.
Here, the team also used germ-free mice with impaired immune systems. Gut microbes, from 4-day old normal mice, were then transplanted.
These mouse were still able to fight off the Salmonella infection without the immune system’s aid. This was only achieved by receiving a dose of added Clostridium first.
“Normally, we acquire Clostridia strains in our guts when we begin to eat solids, but this work suggests a window of vulnerability to enteric pathogens in the early stages of life," said Dr Nunez.
“If the protective role of added Clostridia for newborns bears out in further animal studies, it might be possible to propose a clinical trial in humans to test a combination of strains.”
The study once again highlights the role the gut microbiota plays in the development of the immune system.
Studies have shown the gut microbiota is active in immunoglobulin A secretions, as well as local T-helper 17 cells and regulatory T cells, all components that contribute to the immune response.
The microbiota’s role also extends towards protecting the host against colonisation by external pathogens, a phenomena known as ‘colonisation resistance.’
Published online ahead of print: DOI: 10.1126/science.aag2029
“Neonatal acquisition of Clostridia species protects against colonization by bacterial pathogens.”
Authors: Gabriel Núñez et al.