Episode 29: Human milk oligosaccharides in the infant gut

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.

vinderola in vitro blog

The need to improve in vitro testing of future probiotics

By Prof. Gabriel Vinderola, Instituto de Lactología Industrial (INLAIN, UNL-CONICET), National University of Litoral, Argentina and Prof. Seppo Salminen, Functional Foods Forum, Faculty of Medicine, University of Turku, Finland

In a recent review we compared the in vitro tests for probiotics to the in vivo studies to observe if correlations exist.

Lactobacilli and bifidobacteria have been traditionally accepted as probiotics with the basis of their long history of safe use and reported benefits. However, new species, some of them never previously consumed, are being proposed as probiotic candidates. Some basic tests have been suggested for probiotic candidates, but there is a lack of standardized in vitro protocols for the selection of new strains of probiotics. Additionally, safety assessment of new species may have to cover aspects never hitherto considered.

Vinderola and coworkers reviewed the common in vitro selection tests such as exposure to low pH and bile salts, adherence to intestinal mucus or cell lines and prokaryotic-eukaryotic co-cultures that have been traditionally used to predict the functional properties of probiotics.  At the end, the correlation of in vitro results with in vivo performance remained ambiguous. This poses challenges to research as newly proposed probiotics include often novel species never hitherto administered to humans.

The question of safety has been handled by the European QPS system and the US GRAS notifications but questions on efficacy, particularly concerning health claims, would benefit from predictive in vitro tests. These appear to predict more technological properties than safety and efficacy or health benefits.

New standardized systems need to be developed along with detailed sequencing information to be able to predict novel probiotic properties before they are tested in expensive human intervention studies. If the predictive capacity of in vitro tests fails, many potential probiotics will be left on the way from the laboratory to the application in humans and animals.

The lack of standardized protocols for in vitro and in vivo studies hampers comparison of the potential of new species and strains. There is thus a need to conduct selection of potential probiotics in a more robust manner and to focus on well-defined in vitro and in vivo (animal) studies able to predict health benefits that must still be confirmed in human interventions studies with the smallest possible error margin.

For additional perspective on this issue, see blog by Dr. Mary Ellen Sanders: Probiotic Screening: Are in vitro Tests Informative?



Reference: Vinderola G, Gueimonde M, Gomez-Gallego C, Delfredico L, Salminen S. Correlation between in vitro and in vivo assays in selection of probiotics from traditional species of bacteria. Trends in Food Sci Tech 2017: 68:83-90.