Decoding the Infant Microbiome's Three Pioneers

Researchers discovered that newborns had one of three pioneer bacteria in their stomachs immediately after birth, one of which might be exploited to generate novel personalized infant therapeutic probiotics.

Researchers from the Wellcome Sanger Institute, University College London (UCL), and the University of Birmingham used whole genome sequencing to analyze stool samples from 1,288 healthy infants under the age of one month from the UK Baby Biome Study.

This study, published on September 6th, 2024, in Nature Microbiology, discovered that one of these beneficial bacterial pioneers was genetically modified to fully utilize the nutrients in breast milk, implying that it is best equipped to survive in a baby's microbiome. The researchers discovered that this bacteria can also prevent diseases from invading newborns' guts, indicating its potential as a natural probiotic.

The findings could help in the creation of newborn formulae and therapeutic probiotics with the most effective natural strains for the baby's gut. Currently, most commercial newborn probiotics include a different bacterial strain that is not prevalent in the early microbiomes of infants in industrialized cultures such as the United Kingdom and the United States.

In addition to the two good pioneer bacteria, researchers identified a third bacterium that is deemed dangerous because it can colonize antibiotic-resistant bacteria. This can disrupt the formation of the newborn microbiome and increase the likelihood of infections colonizing the gut.

In the future, it might be feasible to forecast how a baby's gut will grow by scanning its microbiome composition shortly after birth and determining which pioneer bacteria it has. If necessary, a personalized probiotic might be administered to encourage healthy microbiome growth and guard against potentially pathogenic infections.

Further study, such as the Microbes, Milk, Mental Health, and Me (4M) project, is required to understand the influence of pioneer microbes on health. This investigation, co-led by the Wellcome Sanger Institute, is part of the Children Growing Up in Liverpool study, which includes 10,000 mothers and infants.

This broad study aims to investigate how variables such as the newborn gut microbiota and early-life nutrition influence brain development, behavior, emotions, and mental health later in life.

The gut microbiome is a complex ecosystem containing millions of bacteria that are essential for human health and immune system development. Since it begins to form immediately after birth, the first month is the earliest opportunity to intervene with probiotics to repair or strengthen the microbiome.

However, prior to this study, there was a paucity of high-resolution data on how the microbiome develops throughout this period of life, as well as which bacteria would be most beneficial in healthy babies.

Building on a recent UK Baby Biome Study that found that babies delivered vaginally had a distinct microbiome than those born by caesarean5, this current study examined an extended dataset of 2,387 stool samples from 1,288 UK newborns born in hospitals and some of their mothers.

The researchers from the Wellcome Sanger Institute, UCL, and the University of Birmingham discovered that all babies fit into one of three microbiome profiles, each with a distinct dominating pioneer bacterium.

Bifidobacterium longum subsp. longum (B. longum) and Bifidobacterium breve (B. breve) are regarded as advantageous because they support the steady colonization of other beneficial microorganisms, but Enterococcus faecalis (E. faecalis) is considered dangerous.

B. longum was discovered to originate in the mother's stomach after delivery, whereas B. breve was not transferred in this manner6. The researchers also discovered that B. breve is genetically suited to use the nutrients provided in breast milk completely and can prevent potentially harmful infections from colonizing the newborns' stomachs.

Approximately 85 percent of the newborns investigated were breastfed in their first several weeks of life. Researchers discovered that breastfeeding, compared to formula feeding, did not appear to impact the type of pioneer bacteria in the baby's gut, but antibiotic usage did.

Researchers point out that other variables, such as maternal age and number of births, might have a role, but more study is needed to explore this and its influence on long-term health outcomes.

They also discovered that Bifidobacterium longum subsp. infantis, which is widely detected in commercial infant probiotics, was not a pioneer bacterium and is uncommon in UK newborns. This discovery is consistent with studies from other Western industrialized nations, which have similarly found a paucity of naturally occurring B. infantis in early infant microbiomes and implies that B. breve could be a more effective natural probiotic.

If we think of a newborn baby’s gut as an ecosystem that starts to establish right from birth, there was very little known about which and how microbes plant the very first seeds to establish themselves before the findings of the UK Baby Biome Study. By analyzing the high-resolution genomic information from over 1,200 babies, we have identified three pioneer bacteria that drive the development of the gut microbiota, allowing us to group them into infant microbiome profiles.”

Dr Yan Shao, Study First Author, Wellcome Sanger Institute

Dr Yan Shao added, “Being able to see the make-up of these ecosystems and how they differ is the first step in developing effective personalized interventions to help support a healthy microbiome.”

Professor Louise Kenny, Lead Investigator of the Children Growing up in Liverpool study from the University of Liverpool, stated, “Decisions around mode of childbirth and breastfeeding are complex and personal, and it is 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 is also important to note that we still have an incomplete understanding of how the role of the mode of birth and different methods of infant feeding influence microbiome development and how this impacts later health.”

Kenny added, “That is 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, study co-author from UCL, Further added, “While our study has shortlisted three pioneer bacteria as important for babies’ microbiome development, it remains to be determined if and how different pioneer bacteria affect health and diseases, both in childhood and later in life. The UK Baby Biome Study is actively following up with participants to give clues about this, and now even bigger cohorts are needed to investigate the role of the infant microbiome on health.”

Dr Trevor Lawley, Study Senior Author from the Wellcome Sanger Institute added, “The development of the microbiome at the beginning of a person’s life could have huge implications for them later on. It is also a time when the use of infant probiotics could be highly effective if we know what bacteria are both important and relevant to the target populations. Our study highlights a hugely beneficial pioneer bacterium that can fully digest breast milk and protect the newborn against harmful microbes.”

Lawley explained, “This has the potential to be a highly effective natural probiotic as it can already establish itself in the child’s gut, and I hope that our open-access study encourages the rational selection of probiotic strains and development of novel microbiome-based therapeutics built on genomic research.”