Natural probiotics discovered in UK newborn microbiomes

Researchers show that newborn babies have one of three pioneer bacteria in their gut shortly after birth. One of these bacteria could be used to develop new, personalized therapeutic probiotics for babies.

In the largest study of the infant microbiome in the UK to date, researchers from the Wellcome Sanger Institute, University College London (UCL) and the University of Birmingham used whole genome sequencing to analyse stool samples from 1,288 healthy infants, all under one month old from the UK Baby Biome Study.

This research, published in Nature Microbiologydiscovered that one of these beneficial bacterial pioneers was genetically adapted to make full use of the nutrients in breast milk, suggesting that it is best suited to thrive in a baby’s microbiome. The team found that this bacterium can also block pathogens from colonizing the baby’s gut, highlighting its considerable potential as a natural probiotic.

The findings could support the development of infant formulas and therapeutic probiotics that contain the most effective natural strains for the baby’s gut. Currently, most commercial probiotics for infants contain a different strain of bacteria that is absent from the early microbiomes of infants in industrialized societies such as the UK and US.

In addition to the two beneficial pioneer bacteria, researchers highlighted a third bacterium that is considered risky because it can lead to colonization of antibiotic-resistant bacteria. This can disrupt the development of the baby’s microbiome and increase the risk of pathogens colonizing the gut.

In the future, it may be possible to predict how a baby’s gut will develop by mapping their gut microbiome profile immediately after birth to assess which pioneer bacteria they have. If needed, a personalized probiotic could be provided to promote healthy microbiome development and protect against potentially pathogenic infections.

Further research such as the Microbes, Milk, Mental Health and Me (4M) project is needed to understand the impact of pioneer bacteria on health. This project, co-led by the Wellcome Sanger Institute, is part of the Children Growing Up in Liverpool study involving 10,000 mothers and babies. This large-scale study aims to investigate how factors such as the baby’s gut microbiome and nutrition in early life influence brain development, behaviour, emotions and mental health later in life.

The gut microbiome is a complex ecosystem of millions of microbes that are vital to human health and important for the development of the immune system. Because it begins to form immediately after birth, the first month is the earliest window for intervention with probiotics that can be used to restore or strengthen the microbiome. However, prior to this study, there was a lack of high-resolution data showing how the microbiome develops during this period of life and which bacteria would be most beneficial in healthy newborns.

Building on a previous UK Baby Biome Study which showed that babies born vaginally had a different microbiome to those born by caesarean section, this new research analysed a larger dataset of 2,387 stool samples from 1,288 British babies born in hospitals and some of their mothers. The team from the Wellcome Sanger Institute, UCL and the University of Birmingham found that all the newborns fell into one of three microbiome profiles, each characterised by a different dominant pioneer bacteria.

Of these pioneer bacteria, Bifidobacterium longum subsp. longum (B. longum) and Bifidobacterium breve (B. breve) are considered beneficial, as they promote stable colonization of other beneficial microbes. Enterococcus faecalis (E. faecalis) is considered risky.

B. longum was found to have originated in the mother’s gut during childbirth. However, the team found that B. breve was not transmitted in this way. The team also found that B. breve is genetically adapted to fully utilize the nutrients in breast milk and can block potentially harmful pathogens from colonizing the babies’ gut.

About 85 percent of babies studied were breastfed for the first few weeks of life. Researchers found that breastfeeding versus bottle feeding didn’t seem to affect the type of pioneer bacteria in the baby’s gut, but antibiotic use did. Researchers stress that other factors, such as the mother’s age and number of births, may also play a role, but more research is needed to investigate this and its impact on long-term health.

They also showed that a bacterium commonly found in commercial probiotics for babies, known as Bifidobacterium longum subsp. infantis (B. infantis), was not a pioneer bacterium and was rare in British babies. This finding is in line with research from other western industrialised countries that also shows a lack of naturally occurring B. infantis in early baby microbiomes and suggests that B. breve could be a more effective natural probiotic.

Dr Yan Shao, first author from the Wellcome Sanger Institute, said: “Thinking of a newborn baby’s gut as an ecosystem that begins to establish itself from birth, little was known about which and how microbes plant the very first seeds to establish themselves before the findings of the UK Baby Biome Study. By analysing high-resolution genomic information from more than 1,200 babies, we have identified three pioneer bacteria that drive the development of the gut microbiome, allowing us to group them into baby microbiome profiles. Being able to see the composition of these ecosystems and how they differ is the first step in developing effective personalised interventions to support a healthy microbiome.”

Professor Louise Kenny, lead researcher on the Children Growing up in Liverpool study from the University of Liverpool, added: “Decisions about mode of birth and breastfeeding are complex and personal, and it’s important to note that there is no one-size-fits-all approach when it comes to what the best options are for you and your baby. It’s also important to note that we still have an incomplete understanding of how the role of mode of birth and different methods of infant feeding influence the development of the microbiome and how this affects later health. That’s why this research is vital. We must continue to find new ways to ensure that all children are supported to have the best possible start in life.”

Professor Nigel Field, co-author of the study from UCL, commented: “While our study has selected three pioneer bacteria as important for the development of the baby microbiome, it remains to be established whether and how different pioneer bacteria influence health and disease, both in childhood and later in life. The UK Baby Biome Study is actively following participants to provide clues to this, and even larger cohorts are now needed to investigate the role of the baby microbiome in health.”

Dr Trevor Lawley, senior author from the Wellcome Sanger Institute, commented: “The development of a person’s microbiome early in life can have major implications for them later in life. It is also a time when using probiotics for babies can be very effective, if we know which bacteria are both important and relevant to the target group.

“Our study highlights a hugely beneficial pioneer bacterium that can fully digest breast milk and protect the newborn from harmful microbes. This has the potential to be a highly effective natural probiotic as it can already establish itself in the infant’s gut, and I hope our open access study will encourage rational selection of probiotic strains and the development of novel microbiome-based therapies based on genomic research.”