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Episode 29: Human milk oligosaccharides in the infant gut

/in Podcast, Season Two /by Laura

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The Science, Microbes & Health Podcast 

This podcast covers emerging topics and challenges in the science of probiotics, prebiotics, synbiotics, postbiotics and fermented foods. This is the podcast of The International Scientific Association for Probiotics and Prebiotics (ISAPP), a nonprofit scientific organization dedicated to advancing the science of these fields.

Human milk oligosaccharides in the infant gut, with Dr. Simone Renwick PhD

Episode summary:

In this episode, the ISAPP hosts discuss human milk and the infant gut with Dr. Simone Renwick PhD from Mother-Milk-Infant Center of Research Excellence (MOMI CORE) at UC San Diego, USA. Dr. Renwick talks about her work investigating how communities of microbes versus individual microbes in the infant gut metabolize human milk oligosaccharide (HMO) structures, and what we know about the origin and functions of the microbes contained in human milk.

Key topics from this episode:

  • Dr. Renwick studies how components of human milk foster the development of the infant gut microbiota. These components include HMOs (special sugars found in human milk) and the milk microbiota.
  • HMOs cannot be metabolized by the human body, but when microbes in the infant gut break them down, it has health benefits for the infant (because infants who receive no human milk are predisposed to a range of diseases).
  • Dr. Renwick used in vitro models to mimic infant microbiota communities, and found that these communities rapidly degraded the HMOs. This metabolism increased microbes associated with health and suppressed potentially pathogenic microbes. 
  • Although most research on HMOs focuses on bifidobacteria that are specially equipped to break them down, she looked at individual strains within the infant gut community and found approximately 100 species capable of directly degrading HMOs.
  • Once breastfeeding ceases, some microbes in the infant gut adapt to different sources of sugars, but others greatly decrease in abundance.
  • Microbes act differently in a community than on their own. Within a complex community, microbes that are better equipped to degrade the HMOs will act quickly, producing byproducts that are then are available to other members.
  • All of the different in vitro models have their advantages and disadvantages. The spatial relationships of the human body are often missing in in vitro models.
  • Humans appear to have the highest concentration of milk oligosaccharides of any mammal.
  • The milk microbiota is another active area of investigation. Live microbes are present in the mammary gland, but their source is still unknown. They tend to resemble the composition of the microbiota on the skin as well as the infant oral cavity, but curiously, anaerobic bacteria are also found in the milk microbiota. Somehow these microbes may move from the mother’s gut to the milk. These microbes may not directly metabolize HMOs. (See this paper.)
  • Formula companies are beginning to put HMO structures into their products – mainly 2′-Fucosyllactose.

Episode links:

About Dr. Simone Renwick PhD:

Dr. Simone Renwick is the Milk & Microbes postdoctoral fellow at the Mother-Milk-Infant Center of Research Excellence (MOMI CORE) at the University of California, San Diego, USA. Her research focuses on understanding the role of human milk components, such as the human milk oligosaccharides (HMOs) and milk microbiota, in fostering the developing infant gut microbiota. She is also interested in the potential therapeutic applications of milk components in diseases that affect adults. Currently, Simone is supervised by Drs. Lars Bode, Rob Knight, Pieter Dorrestein, and Jack Gilbert. Prior to her postdoc, Simone completed her PhD in Molecular and Cellular Biology (MCB) at the University of Guelph, Canada, under the supervision of Dr. Emma Allen-Vercoe.

She was the recipient of the Students and Fellows Association poster prize at the ISAPP 2023 meeting in Sitges, Spain.

A pediatrician’s perspective on c-section births and the gut microbiome

/in Consumer Blog, ISAPP Science Blog /by KC

By Prof. Hania Szajewska, MD, Medical University of Warsaw, Poland and Kristina Campbell, MSc, ISAPP Consulting Communications Director

The decision to have a Cesarean section (C-section) should always depend on whether this is the best choice for the mother and baby, and it is never made by pediatricians. However, pediatricians are often asked about the consequences of C-section delivery for a child later in life and whether potential C-section-related harms may be reduced.

The data show that delivery by C-section is now more common than ever globally. The World Health Organization estimates the  C-section rate is around 21% of all births, and predicted to continue increasing. Although C-section rates are increasing both in developed and developing countries, Korea, Chile, Mexico, and Turkey have the highest rates in the world, with C-sections constituting 45% to 53% of all births. C-sections outnumber vaginal births in countries that include Dominican Republic, Brazil, Cyprus, Egypt, and Turkey.

Cesarean delivery is a medical procedure that can of course save an infant (or a mother) in a moment of danger, making birth less risky overall. But analyses have shown not all C-sections are initiated for safety reasons—some are driven by convenience and other non-medical factors. In areas with the highest C-section rates, only around half of the time are they required for life-saving reasons. Although the rate of medically necessary C-sections globally is difficult to establish, the WHO estimates it is between 10-15% of all births.

Non-essential C-sections would be perfectly reasonable if the health risks later in life were negligible. But are they? Scientific work in the past decade has shown that, in fact, there may be downsides to being born by C-section—and these health risks may manifest later in a child’s life.

By now, many observational studies have associated Cesarean births with an increased risk of various chronic health conditions that appear long after birth. C-section is associated with a higher risk of asthma and allergy, as well as obesity and type 2 diabetes. A systematic review and meta-analysis (incorporating 61 studies, which together included more than 20 million deliveries) also linked C-sections with autism spectrum disorders and attention deficit hyperactivity disorder (ADHD). Type 1 diabetes is also more prevalent in children born by c-section.

Since association is not the same as causation, scientists have looked at possible biological correlates of C-section and how they could be tied to future health problems. A leading hypothesis is that C-section deliveries cause health problems by disrupting the infant’s normal gut microbiota (i.e. the collection of microorganisms in specific ‘habitats’ on the infant’s body, such as the gut) within a critical time window for immune system development.

An altered microbiota in C-section births

One of the main clues about whether C-section births affect health via the microbiota is the consistent observation that infants born by C-section have a different collection of microorganisms in their digestive tracts and elsewhere on their bodies immediately after birth, compared with vaginally-born controls. Newborns delivered by C-section tend to harbor in their guts disease-causing microbes commonly found in hospitals (e.g. Enterococcus and Klebsiella), and lack strains of gut bacteria found in healthy children (e.g. Bacteroides species). Because it is known that gut microbiota are in close communication with the immune system, this difference in birth microbes may set the immune system up for later dysfunction.

However, an important confounding factor exists. Antibiotic administration is a recommended medical practice for C-section births in order to prevent infections. Antibiotics are potent disruptors of microbial communities – in this case the mother’s, or perhaps the infant’s if antibiotics are administered prior to umbilical cord clamping. It is not yet clear whether the timing of antibiotic administration can prevent such disruptions. (See conflicting evidence here and here; also see here.).

Gut microbiota disruption is associated with C-sections, but since C-section and antibiotics nearly always go together (with potential exposure of the infant to these drugs), it is not clear to what extent C-section and/or antibiotic treatments drive increased risk of chronic disease later in life. Antibiotic treatments within the first 2 years of life are independently associated with an increased risk of several conditions: childhood-onset asthma, allergic rhinitis, atopic dermatitis, celiac disease, overweight / obesity, and ADHD.

Options for microbiota ‘restoration’

If mechanistic studies continue to support the idea that the C-section-disrupted gut microbiota is the trigger for chronic diseases later in life, strategies could be proposed for ‘restoring’ or normalizing the infant gut microbiota after such births. Already some microbiota modifying interventions have been evaluated:

  • Probiotics: Undesired changes in microbiota composition and function caused by antibiotic treatments and/or caesarean birth may be addressed by probiotics—i.e. “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. In one study, a mixture of several probiotic strains along with at least partial breastfeeding shifted the infant gut microbiota toward a more favorable profile. Intriguingly, probiotics (of various strains) prevent IgE-associated allergy until age 5 years, specifically in cesarean-delivered children but not in all children.
  • Synbiotics: A study showed supplementation with scGOS/lcFOS and B. breve M-16V appeared to compensate for delayed Bifidobacterium colonization in the guts of C-section delivered infants.
  • Maternal vaginal microbial transfer (otherwise known as ‘vaginal seeding’ or ‘microbial bath’: This is a procedure in which infants born by C-section, immediately after birth, are swabbed with gauze that contains microbes from the mother’s vaginal tract. After the media attention given to early studies, there is increased demand from parents for this procedure. Although some studies have found it effective for normalizing the infant gut microbiota, safety is not completely established and it is too early for routine use of this procedure. Parents wishing to try this approach are advised to participate in a study as part of an institutional review board-approved research protocol.
  • Maternal fecal microbiota transplantation: This procedure involves fecal microbes from the mother, orally administered to C-section infants after birth. A proof-of-concept study showed that after this intervention the gut microbiota of C-section-born infants looked more similar to that of vaginally born infants. But for this procedure, as above, the risk of transmitting harmful microbes is a concern, making it too early to recommend the procedure unless it is part of an institutional review board-approved research protocol.
  • Breastfeeding: Breastfeeding is the gold standard for infant nutrition, and breast milk contains live microorganisms as well as other components that interact with the gut microbiota. Exclusive breastfeeding for about 6 months of C-section infants helps the gut microbiota shift toward a profile seen in vaginally born infants.

So far, probiotics, synbiotics, and microbiota ‘restoration’ are not sufficiently reliable solutions for correcting the microbiota disruptions that accompany C-section births. Further studies are needed to develop these approaches.

A leading strategy

At present, breastfeeding is the main strategy for supporting the infant gut microbiota after C-section for the greatest chance of avoiding negative health consequences. Breastfeeding has multiple benefits, but may be of increased importance after C-section birth. Mothers should be supported after giving birth by C-section to breastfeed the infant during this critical period of early life and immune system development.