Natural probiotic discovered in UK newborns’ microbiomes
In a very nice example of how humans and their gut microbiome have co-evolved, researchers from the Wellcome Sanger Institute, University College London (UCL), and the University of Birmingham, have identified a bacterium that helps digest breast milk and protects the baby from harmful pathogens.
As an example of intelligent [sic] design, this comes as close to a Heath-Robinson solution to a problem of the designer's own making as it's possible to imagine.
No designer who designed a baby's digestive system so it is susceptible to the harmful pathogens that it also designed, and created the baby to feed on breast milk that is difficult to digest, then solved those problems by creating another bacterium to fight the pathogens and help digest the milk, and infecting the baby with it, doesn't deserve the adjective 'intelligent'. 'Bloody stupid' would be a more appropriate term.
It's almost exactly as though the designer of these systems is a mindless automaton, simply obeying the natural laws of chemistry and physics and working without a plan!
The researchers have completed the largest study of UK baby microbiomes to date, carrying out whole genome sequencing to analyse stool samples from 1,288 healthy infants, all under one month old from the UK Baby Biome Study1.1.
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What can you tell me about how the human gut microbiome develops including how newborn babies acquire their gut microbes? The human gut microbiome is a complex community of trillions of microorganisms, including bacteria, fungi, viruses, and archaea, that reside in the gastrointestinal tract. It plays a crucial role in human health by aiding digestion, producing essential nutrients, supporting immune function, and protecting against harmful pathogens. The development of the gut microbiome begins at birth and continues to evolve throughout a person's life.
Development of the Gut Microbiome in NewbornsMaturation and Stability of the Gut Microbiome
- Initial Colonization at Birth:
Newborns begin acquiring their gut microbes during birth. The mode of delivery significantly influences this initial microbial colonization:
- Vaginal Birth: Babies born vaginally are primarily exposed to their mother's vaginal and fecal microbiota, which includes beneficial bacteria such as Lactobacillus and Bifidobacterium. These bacteria help to establish the infant’s gut microbiome.
- Cesarean Section (C-Section): Babies delivered by C-section tend to acquire microbes from the mother’s skin, the environment, and healthcare personnel, rather than from the birth canal. This can result in a different microbial profile, often with lower levels of Lactobacillus and Bifidobacterium and a delayed maturation of the gut microbiome.
- Influence of Feeding Practices:
After birth, feeding practices play a major role in shaping the infant's gut microbiome:
- Breastfeeding: Breast milk contains beneficial bacteria (such as Bifidobacterium species), human milk oligosaccharides (HMOs), and other bioactive components that promote the growth of beneficial microbes. HMOs, in particular, serve as prebiotics that selectively feed beneficial bacteria in the gut, such as Bifidobacterium.
- Formula Feeding: Formula-fed infants tend to have a more diverse microbiome with higher levels of Clostridium and Bacteroides species and lower levels of Bifidobacterium. The microbial composition in formula-fed babies can also be influenced by the specific formulation of the formula.
- Introduction of Solid Foods:
Around 4-6 months of age, when solid foods are introduced, there is a significant shift in the gut microbiome composition. The diversity of microbes increases, and bacteria that are better suited to digest a more complex diet (including Bacteroides and Firmicutes) become more prevalent. This period is crucial as it marks a transition from a milk-based diet to one that includes a variety of foods.
- Environmental Factors:
Several environmental factors also contribute to the development of the gut microbiome:
- Antibiotic Exposure: Antibiotics can disrupt the gut microbiome by killing both harmful and beneficial bacteria. Infants exposed to antibiotics (either directly or through the mother) tend to have a less diverse microbiome, and this disruption can have lasting effects on health.
- Family and Home Environment: The microbiome of family members, pets, and the overall home environment can influence the microbial diversity in infants. Early life exposures to various microorganisms from siblings, pets, and other household members can promote a more diverse and resilient gut microbiome.
- Geographic and Cultural Factors: Geographic location, cultural practices, and diet also play a role in the development of the infant gut microbiome. Studies have shown differences in the microbiomes of infants from rural versus urban settings, likely due to differences in diet, sanitation, and lifestyle.
As children grow, their gut microbiome continues to develop and stabilize, reaching an adult-like composition by around 3 years of age. The early years are critical because the composition and diversity of the microbiome can impact immune development, metabolism, and the risk of developing certain diseases later in life, such as allergies, asthma, obesity, and autoimmune disorders.
Key Takeaways
Would you like to know more about any specific aspect of the gut microbiome development?
- The gut microbiome begins developing at birth, influenced by delivery mode, feeding practices, and environmental exposures.
- The first few years of life are crucial for microbiome development, with significant changes occurring during birth, breastfeeding, the introduction of solid foods, and exposure to the environment.
- A diverse and balanced gut microbiome is essential for health, particularly for immune function, metabolism, and resistance to disease.
Natural probiotic discovered in UK newborns' microbiomes
In the largest genomic analysis of UK infant microbiomes to date, researchers have uncovered a type of bacterium that helps digest breast milk and protects a baby's gut from pathogens.
Newborn babies have one of three pioneer bacteria in their gut shortly after birth, one of which could be used to develop new personalised infant therapeutic probiotics, researchers show.
In the largest study of UK baby microbiomes 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 Study1.1.
This research, published today (6 September) in Nature Microbiology, found that one of these beneficial bacterial pioneers was genetically adapted to make full use of the nutrients in breast milk, suggesting that it is the most suited to thrive in a baby’s microbiome. The team uncovered that this bacterium can also block pathogens from colonising the babies’ gut, highlighting its significant potential as a natural probiotic.
The findings could support the development of infant formulas and therapeutic probiotics containing the most effective natural strains for the baby’s gut. Currently, most commercial infant probiotics contain a different bacterial strain not found in the early microbiomes of infants in industrialised societies like the UK and the US2.1,3.1.
In addition to the two beneficial pioneer bacteria, researchers highlighted a third bacterium that is considered risky as it can lead to the colonisation of antibiotic-resistant bacteria. This can interfere with the development of the infant microbiome and increase the risk of pathogens colonising the gut.
In the future, it could be possible to predict how a baby’s gut will develop by mapping their gut microbiome profile right after birth to assess which pioneer bacteria they have. If needed, a personalised probiotic could be provided to help 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.4.1 This project, co-led by the Wellcome Sanger Institute, is part of the Children Growing Up in Liverpool study involving 10,000 mothers and infants. This extensive research seeks to explore how factors such as the infant gut microbiome and early life feeding affect brain development, behaviour, emotions and mental health later in life.
The gut microbiome is a complex ecosystem of millions of microbes that are vital for human health and important in immune system development. As it begins to form immediately at birth, the first month is the earliest window for intervention with probiotics that could be used to restore or boost the microbiome. However, before this study, there was a lack of high-resolution data showing how the microbiome develops in this period of life, and which bacteria would be the most useful in healthy newborns.
Building on a previous UK Baby Biome Study that showed babies born by vaginal birth had a different microbiome compared to those born via caesarean5.1, this new research analysed an expanded dataset of 2,387 stool samples from 1,288 UK infants born in hospitals and some of their mothers. The team from the Wellcome Sanger Institute, UCL, and the University of Birmingham, found that all newborns fell into one of three microbiome profiles, each characterised by a different dominant pioneer bacterium.
Out of these pioneer bacteria, Bifidobacterium longum subsp. longum (B. longum) and Bifidobacterium breve (B. breve) are considered beneficial as they promote the stable colonisation of other beneficial microbes, and Enterococcus faecalis (E. faecalis) is considered risky.
B. longum was found to come from the mother’s gut during childbirth, however, the team found that B. breve was not transmitted in this way6.1. The team also uncovered that B. breve was genetically adapted to fully utilise the nutrients found in breast milk and can block potentially damaging pathogens from colonising the babies’ guts.
Around 85 per cent of the babies studied were breastfed in the first few weeks of life. Researchers found that breastfeeding versus formula feeding did not seem to influence the type of pioneer bacteria in the baby’s gut, however the use of antibiotics did7.1. Researchers highlight that other factors such as maternal age and how many times someone has given birth may also play a role, but further research is needed to investigate this and the impact on long-term health outcomes.
They also showed that a bacterium commonly found in commercial infant probiotics known as Bifidobacterium longum subsp. infantis (B. infantis) was not a pioneer bacterium, and is rare in UK infants. This finding is aligned with research from other Western industrialised countries that also shows a lack of naturally occurring B. infantis in early infant microbiomes2.1,3.1 and suggests 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 analysing 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. Being able to see the make-up of these ecosystems and how they differ is the first step in developing effective personalised interventions to help support a healthy microbiome.
Dr Yan Shao, first author
Wellcome Sanger Institute.Decisions around mode of childbirth 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 is 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 microbiome development and how this impacts 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 Louise Kenny,
Lead Investigator of the Children Growing up in Liverpool study
University of Liverpool.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 participants to give clues about this, and now even bigger cohorts are needed to investigate the role of the infant microbiome on health.
Professor Nigel Field, co-author
UCL.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. 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.
Dr Trevor Lawley, senior author
Wellcome Sanger Institute.
AbstractAs though to emphasise the hit and miss nature of what creationists will insist is an intelligently designed system, in their discussion, the authors say:
Human microbiota assembly commences at birth, seeded by both maternal and environmental microorganisms. Ecological theory postulates that primary colonizers dictate microbial community assembly outcomes, yet such microbial priority effects in the human gut remain underexplored. Here using longitudinal faecal metagenomics, we characterized neonatal microbiota assembly for a cohort of 1,288 neonates from the UK. We show that the pioneering neonatal gut microbiota can be stratified into one of three distinct community states, each dominated by a single microbial species and influenced by clinical and host factors, such as maternal age, ethnicity and parity. A community state dominated by Enterococcus faecalis displayed stochastic microbiota assembly with persistent high pathogen loads into infancy. In contrast, community states dominated by Bifidobacterium, specifically B. longum and particularly B. breve, exhibited a stable assembly trajectory and long-term pathogen colonization resistance, probably due to strain-specific functional adaptions to a breast milk-rich neonatal diet. Consistent with our human cohort observation, B. breve demonstrated priority effects and conferred pathogen colonization resistance in a germ-free mouse model. Our findings solidify the crucial role of Bifidobacteria as primary colonizers in shaping the microbiota assembly and functions in early life.
Main
Human gut microbiota colonization commences immediately at birth when neonates are exposed to microorganisms from the surrounding environment and maternal sources (for example, gut1,2,3,4,5, vagina2,3,4, skin3,4, breast milk3,6). We recently reported in the UK Baby Biome Study (BBS) that maternal transmission of primary colonizers, such as commensal Bifidobacterium and Bacteroides species, is disrupted in caesarean-section (CS) and antibiotic-exposed births, instead predisposing the neonatal gut microbiota (NGM) to colonization by antibiotic resistant healthcare-associated pathogens1. This observation suggests the possibility of ‘priority effects’ in human gut microbiota assembly, which posits the arrival order of primary colonizer species determines the outcome of the microbiota assembly during a primary ecological succession (from sterile to complex communities)7,8. The NGM represents the earliest window of opportunity for intervention with probiotics or prebiotics to prevent or restore impaired microbiota development. However, little is known about the ecological priority effects in the NGM assembly due to a lack of high-resolution, longitudinal human microbiome data from the neonatal period (that is, the first month of life).
DiscussionI wonder if i can tempt a creationist to try to explain the intelligence behind creating babies with a gut that can harbour harmful pathogens and designing them to live on breast milk which is hard to digest, then solving those design problems by designing bacteria to colonise the gut to keep the pathogens down and to help digest the milk.
In presumably the largest neonatal gut metagenome study ever undertaken, we discovered three distinct NGM community states in over 1,000 healthy, full-term neonates drawn from the general UK population, representing diverse ethnicities and sociodemographic backgrounds. Factors that may influence the maternal gut microbiota, such as maternal age, ethnicity and parity, as well as events that influence its vertical transmission to the neonatal gut during the perinatal period (for example, CS and maternal antibiotics), serve as independent determinants of the acquisition of primary colonizers. The presence of a highly unstable community state (EF) with AMR-enriched opportunistic pathogens underscores the hospital environments and practices, such as maternal antibiotics during labour and elective CS births, as important risk factors1,35,36,37,38. Although antibiotics after birth and breastfeeding are known important factors shaping the later infant-stage microbiome development13,15,39,40, these postnatal factors had no observable effect on very early NGM dynamics on either the acquisition or the switching of the NGM community states. Together, our findings highlight that the NGM assembly outcome is highly dependent on the succession of primary colonizer species, with prenatal and perinatal factors associated with birth exerting profound influences…
Would it not have been more intelligent not to design the problems in the first place, or are we supposed to admire the designer's ingenuity in its Heath-Robinson solution to problems it designed in the first place?
I'm assuming, of course, that a creationist would use the same definition of intelligence as that used by normal people in everyday speech and not a private one that means 'bloody stupid and incompetent' in normal English.
The Unintelligent Designer: Refuting The Intelligent Design Hoax
The Malevolent Designer: Why Nature's God is Not Good
Illustrated by Catherine Webber-Hounslow.
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