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Episode 38: Microbes that break down mucus and milk to benefit the host, with Dr. Clara Belzer PhD

/in Podcast, Season Three /by Laura

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We discuss microbes, mucus, and milk with Dr. Clara Belzer PhD from Wageningen University in the Netherlands in this episode. Dr. Belzer, a molecular geneticist, specializes in studying the microorganisms that are equipped to break down the glycans in mucus and human milk within the host environment.

Key topics from this episode:

  • Dr. Belzer’s research focuses on the microbes living in the host that survive on glycans (chains of sugars) produced by the host: milk oligosaccharides and mucus. The host is not good at digesting these sugars, but can use them when they’re separated into smaller components. These long chains of sugars end up in the large intestine, where certain microbes begin to digest them.
  • There seems to be an evolutionary adaptation that sustains the symbiotic relationship between human milk and bacteria in the infant gut; many immune molecules in the human milk suppress pathogens, so the human milk oligosaccharides (HMOs) are available to the bacteria in the infant gut that can break them down. The bacteria are not suppressed by the acidic environment in the infant gut.
  • Human milk is the best food for infants, but innovations in infant formula may make it more similar to human milk.
  • Akkermansia is a genus of bacteria mostly found in adults, but also sometimes in infants, which grows in the mucosal layer of the intestines. (It doesn’t survive on dietary glycans.) Dr. Belzer’s hypothesis is that the environment created by human milk in the infant gut also fosters bacteria that can grow on mucus, creating a succession of host-benefitting bacteria. They found that HMOs, in addition to mucus, can support the growth and survival of Akkermansia, potentially helping it build a microbial network.
  • There’s a genetic component to the HMOs contained in human milk; similarly, the sugar content in the mucosal glycans is related to host genetics.
  • Lean individuals have a higher abundance of Akkermansia; these bacteria improve metabolism (for example, increasing insulin sensitivity) and have effects on the immune system, which both contribute to a lean phenotype. The root of these effects may be the strengthening of the gut barrier, which dampens signals from the lumen.
  • Dr. Belzer has used both omics and culture-based approaches in her research. As part of her research she tries to make microbial synthetic communities, growing them in the lab and stimulating them with different glycans. This technique yields insights about the functions and microbial ecology in the gut.
  • Killed Akkermansia are still able to bring health benefits to the host. Dr. Belzer had the idea that the pili structures on the bacteria were what communicated with the host, and sure enough, this was borne out in a study that showed the proteins in the pili (Amuc_1100) remained intact in the pasteurized bacteria and could stimulate the host immune system. This is a valuable finding because Akkermansia are difficult to culture.
  • When Akkermansia fails to occupy the niche in the mucus layer, Bacteroides species may occupy the niche instead, forming a different microbial community in the mucus. Research is ongoing about the effects of different microbes carrying out similar functions for the host. Furthermore, scientists have many more microbial functions to discover.

Episode abbreviations and links:

About Dr. Clara Belzer PhD:

Dr. Clara Belzer is Associate Professor Microbiology at the Laboratory of Microbiology of Wageningen University. The Belzer group is called ‘Microbes Mucus and Milk’ and the research is focused on the interaction of the gut microbiome with host mucus and milk. After obtaining her PhD at the Erasmus Medical Center Dr. Belzer did a postdoc at Harvard medical school. By now Dr. Belzer has years of experience on gut microbiome studies on anaerobes, including synthetic communities and different biotic concepts, with a special interest for the Akkermansia muciniphila. The group of Dr. Belzer works on several microbiome HMO and mucus related topics funded by national and international grants, some also in collaboration with medical centers and industry.

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.

New publication co-authored by ISAPP board members gives an overview of probiotics, prebiotics, synbiotics, and postbiotics in infant formula

/in News, ISAPP Science Blog /by KC

For meeting the nutritional needs of infants and supporting early development, human milk is the ideal food—and this is reflected in breastfeeding guidelines around the world, including the World Health Organization’s recommendation that babies receive human milk exclusively for the first six months of life and that breastfeeding be continued, along with complementary foods, up to two years of age or beyond. In certain cases, however, breastfeeding is challenging or may not even be an option. Then, parents rely on alternatives for feeding their infants.

A group of scientists, including three ISAPP board members, recently co-authored an article in the journal Nutrients entitled Infant Formula Supplemented with Biotics: Current Knowledge and Future Perspectives. In the review, they aimed to highlight the new technologies and ingredients that are allowing infant formula to better approximate the composition of human milk. They focused on four types of ingredients: probiotics, prebiotics, synbiotics, and postbiotics.

Co-author Gabriel Vinderola, Associate Professor of Microbiology at the Faculty of Chemical Engineering from the National University of Litoral and Principal Researcher from CONICET at Dairy Products Institute (CONICET-UNL) in Santa Fe, Argentina says, “Modern technologies have allowed the production of specific microbes, subtrates selectively used by the host microbes, and even non-viable microbes and their metabolites and cell fragments—for which scientific evidence is available on their effects on infant health, when administered in adequate amounts. Thus, this current set of gut modulators can be delivered by infant formula when breastfeeding is limited or when it is not an option.”

The authors say a well-functioning gut microbiota is essential for the overall health and proper development of the infant, and components of human milk support the development of this microbiota. They list important human milk components and the novel ingredients that aim to mimic the functions of these components in infant formulas:

  • Human milk oligosaccharides (HMOs)

HMOs are specialized complex carbohydrates found in human milk, which are digested in the infant colon and serve as substrates for beneficial microbes, mainly bifidobacteria, residing there. In recent years, prebiotic mixtures of oligosaccharides (e.g. short-chain GOS and long-chain FOS) have been added to infant formula to recapitulate the effects of HMOs. But now that it’s possible to produce several types of HMOs synthetically, some infant formulas are enriched with purified HMOs: 2’-fucosyllactose (2’FL) or lacto-N-neotetraose (LNnT). Even 3′-galactosyllactose (3′-GL) can be naturally produced by a fermentation process in certain infant formulas.

  • Human milk microbiota

Human milk has a complex microbiota, which is an important source of beneficial bacteria to the infant. Studies support the notion that the human milk microbiota delivers bioactive components that support the development of the infant’s immune system. Probiotic strains are sometimes added to infant formula in order to substitute for important members of the milk microbiota.

  • Bacterial metabolites

Human milk also contains metabolic byproducts of bacteria called “metabolites” in addition to the bacteria themselves. These components have not been fully studied to date, but bacterial metabolites such as butyrate and other short-chain fatty acids may have important health effects for the overall development of the infant. A future area of nutritional research is likely to be the addition of ‘postbiotics’ — non-viable cells, their metabolites and cell components that, when administered in adequate amounts, promote health and well-being — to infant formulas. (ISAPP convened a scientific consensus panel on the definition of postbiotics, with publication of this definition expected by the end of 2020.)

 

The precise short- and long-term health benefits of adding the above ingredients to infant formula are still under study. One pediatric society (the ESPGHAN Committee on Nutrition) examined the data in 2011 and at that time did not recommend the routine use of infant formulas with added probiotic and/or prebiotic components until further trials were conducted. A systematic review concluded that evidence for the health benefits of fermented infant formula (compared with standard infant formula) are unclear, although improvements in infant gastrointestinal symptoms cannot be ruled out. Although infant formulas are undoubtedly improving, review co-author Hania Szajewska, MD, Professor of Paediatrics at The Medical University of Warsaw, Poland, says, “Matching human milk is challenging. Any alternative should not only match human milk composition, but should also match breastfeeding performance, including how it affects infant growth rate and other functions, such as the immune response.”