October 28, 2022 9 min read
The moment we are born, we become a sitting target for invasion. Waiting to pounce is a myriad of potentially harmful pathogens ready to pass on a variety of communicable diseases. At this point, one of our main sources of defence is the gut microbiota that we have acquired from our mother before and during birth.
There are several factors that will influence these microbial colonies, including the route of birth, be it vaginal or caesarean section, the level of cleanliness of the environment, and how we will be fed, either by breast or formula. For our microbiota to operate and fully protect us, they will need reinforcements which come from the “food” we consume as neonates[i].
As we grow and develop, our intestinal microbiota consists of a variety of species, but in the short period after birth, it is dominated by Bifidobacteria and Bacteroides. Both are friendly to the host, but their growth and establishment will be determined by several factors, especially nourishment in the form of the foods we receive[ii].
After giving birth, the mother will begin to lactate and produce milk. It is this product that not only provides essential nutrition but also feeds the bacteria within the gut. The process enables existing commensal colonies to grow and flourish.
There is an accumulating amount of research evidence that has established human milk oligosaccharides (HMOs), the third most abundant nutrient within human milk, as the main component for the feeding and development of these very important colonies.
In this article, we will use a short review conducted by Spicer et al.(2022) to understand how HMOs can fight bad bacteria.
The review investigates the bacterial resistance to antibiotics that has evolved since the 1940s when they were first prescribed and how antimicrobial properties of HMOs are being developed to combat this[iii].
The World Health Organisation (WHO) recommends that neonates should be fed on a diet of human milk for the first six months. From around six months, an infant’s diet should be supplemented with solid foods until the age of two.
The importance of human milk consumption by neonates is reiterated by the United States Centre for Disease Control, which states that ‘human milk is the cornerstone of infant nutrition.’ However, globally only around 40% of babies receive human milk as their primary nutrition source.
According to a study by Ogbuanu et al. (2009), the reasons for this include:
In the absence of human milk, the infant is more susceptible to health issues, both as a child and into adulthood. Even formula-fed babies, compared to breastfed babies, have been shown to have an elevated risk of obesity, type 2 diabetes, and respiratory illnesses like asthma[v].
Yet, human milk is packed full of molecules that help control inflammation, invasion from pathogens, and the immune system in general, as well as hundreds of species of friendly bacteria. The review by Spicer et al. (2022) helps to highlight the role HMOs have in fighting bad bacteria and ultimately promoting human health.
So far, around 200 HMOs have been characterised, each containing between 3 and 22 monosaccharides (sugars). Each one also has lactose, a sugar present in milk, at the end of the molecule, also known as the reducing end. HMOs change over the course of lactation; this is also from mother to mother. The mother’s Lewis blood group and secretor status appear to control the fucosylation (the process of transferring fructose) and sialylation, which is essential in cell functions, signal recognition, cell adhesion, and also pathogen recognition by the HMOs[vi][vii].
The composition of human milk changes to meet the needs of the neonate. For example, during the first week of life, colostrum, a non-nutritious early breast milk, is produced to aid immunity. However, by week four, the infant’s diet consists of mature nutritious breast milk. During this early period, HMOs are at their peak and are a vital energy source for commensal bacteria and help keep pathogens at bay.
Further studies have demonstrated the protective advantages breastfed babies have. For example, a study by the American Academy of Paediatrics (AAP) showed that breastfed infants had a lower prevalence of gastrointestinal and respiratory diseases, such as asthma as well as diabetes, compared to formula-fed babies.[viii]
Babies who are delivered vaginally are introduced to their first microbes as they enter the world, also known as a bacterial baptism.Human milk is the second introduction and develops the early gut microbiota. The gut flora of babies who are formula-fed is different to those who are breastfed by their mother. Although formula bottle-fed babies may have increased diversity, the probiotic genus Bifidobacterium often dominates the gut microbiomes of breastfed infants. HMOs, help to change this during the later stages of lactation to Bacteroides[ix].
A human milk gut microbiome reduces infection through the:
The review by Spicer et al. (2022) describes how HMOs can promote the growth of beneficial bacteria but limit or prevent the growth of pathogens, such as Streptococcus agalactiae, also known as Strep B, and Clostridiodes difficile.
Some mothers, approximately 15-30%, are carriers of Group B Streptococcus (GBS).Although many go on to deliver healthy babies, there is a risk that this pathogenic bacterium can be passed to the infant which is responsible for sepsis and meningitis[xiii][xiv].
In the western world, pre-natal screening for GBS is offered to expectant mothers, and if present, antibiotics are prescribed. In a study by Ackerman et al. (2017), HMOs were shown to possess antimicrobial activity against GBS, highlighting their potential as an alternative to traditional antibiotics[xv].
C. difficileinfection is commonly caused by an imbalance in the microbiome after antibiotic use. The infection is caused Clostridiodes difficile, a gram-positive and spore-forming bacteria. The symptoms of the infection vary, but its recurrence rates are high, between 25 and 60% following the first infection, and severe cases can cause life-threatening colitis[xvi].
Interventions such as intestinal microbiota transplantation have been successful and highlight how important the microbiome of the host is. But further research has investigated if and how HMOs can control dysbiosis and prevent the growth of C. difficile.
In a study by Bajic et al. (2021), HMOs were shown to have antimicrobial activity against C Difficile[xvii]. Although the reasons for this are unclear, the authors suggested that the production of short-chain fatty acids (SCFAs) and secondary bile acids, both of which are major bacterial metabolites within the colon[xviii], may explain the role of HMO in modulating dysbiosis.
Pathogens have developed a mechanism of protection and a way to infiltrate cells, this is called a biofilm. Biofilm is a state in which pathogenic bacteria cells can exist in an extracellular matrix where they are protected from antibiotics and can lead to antibiotic resistance. In other words, a biofilm is where microbial cells stick to each other and to another surface[xix], tooth plaque is an example of a visible biofilm.
Antibiotic resistance has become a serious threat to human health, and so there is a need for tools to disrupt the behaviours within pathogenic bacteria that can promote it. HMOs have already been shown to have antiadhesive antimicrobial capabilities, so let’s look at how they could be used to be biofilm disruptors[xx].
S. aureus is a gram-positive bacterium commonly found in the upper part of the throat just behind the nose, called the nasopharynx and on the skin. Approximately 30% of people naturally carryS aureus,but as soon as it becomes pathogenically activated, it can cause:
Interestingly, in 1942 the first penicillin-resistant strain of S. aureus was discovered,[xxi] and its increasing incidence of antibiotic resistance means it is of particular interest. Mainly because the ability of bacteria to evade antibiotic therapy is a threat to human health.
S. aureusis a robust bacterial biofilm producer and is often the cause of medical device-related infections. In a landmark study, it was shown that HMOs can significantly prevent the growth of S. aureus. Additionally, a study by Jarzynka et al. (2022) found that although HMOs didn’t reduce the activity of S. aureus, they did demonstrate a reduction in the number of viable cells in its biofilm[xxii].
As well as being an inhabitant of the vagina, Strep B is also a good biofilm producer. So far, laboratory-based experiments using amine-modified HMOs, including the most common and a Layer Origin Nutrition favourite, 2’-fucosyllactose, have shown impressive antibiofilm activity against S. agalactiae or Strep B[xxiii].
Entero-pathogenic E. coli(EPEC) is a group of E. coliat the centre of a 1940s and 1950s epidemic of sporadic infant diarrhoea. In developing countries, it is a known contaminant of water sources and has a high death rate in infants. EPECis a pathogen that adheres to the gut lining, forming distinct colonies. In a study by Manthey et al. (2014), the antiadhesive properties of HMOs against this type of E. coliwere tested. It was found that in vitrosupplementation of HMOs into cell culture media significantly reduced the attachment of E.coli.The study also found that administering HMOs to newborn mice who were subsequently infected with EPEC saw a reduction in the colonisation of this pathogen[xxiv].
Acinetobacter baumannii is a gram-negative bacterium known for its multidrug resistance. Currently, it is classified as an urgent health threat and can cause numerous severe infections, including:
Once again, laboratory trials have shown that HMOs can disrupt and significantly reduce bacterial biofilms in A. baumannii[xxv].
From birth, HMOs are significant in gut microbiome development, immunity and overall protection. Current research shows that HMOs are pivotal in regulating the composition of the gut microbiome, preventing the growth of pathogens and modulating dysbiosis. However, they may also offer alternatives to antibiotics and could, in the future, help to combat antibiotic resistance.
As well as reducing the growth of pathogenic bacteria, ongoing research shows that HMOs are also important in biofilm reduction, particularly against urgent health threats like A. baumannii.
Remember, you can help to promote the diversity of your own gut microbiome with the PureHMO range from Layer Origin Nutrition.
Written by: Leanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome.
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