2’-FL: Study uncovers impact of DuPont HMO on gut microbiota and metabolite production

09 Oct 2019 --- A new DuPont study has uncovered some of the prebiotic mechanisms behind its product Care4U 2’-Fucosyllactose (2’-FL). The study found that it beneficially changes microbiota composition and the production of microbial metabolites compared to galacto-oligosaccharides (GOS) and lactose. The effects elicited to microbiota and metabolite composition by 2’-FL were between the responses evoked by GOS and lactose, which indicates that 2’-FL is selectively fermented by the infant microbes.

“The data shows that 2’-FL gets fermented in the colon in a manner that is subtle and the fermentation that happens also produces beneficial metabolites, such as acetate, which is known to lower the gastrointestinal pH and decrease the growth of pathogenic bacteria in the gut. We could observe that there was no pathogenic bacterial growth and that there was some beneficial bacterial growth,” Dr. Heli Anglenius, Senior Scientist, DuPont Nutrition & Biosciences, tells NutritionInsight. 

The researchers used their EnteroMIX infant gut simulator to compare the fermentation of carbohydrates between each other. Previously, this same simulator had been used to study the effects of probiotics and prebiotics using adult faecal sample donors. However, this new study is the first usage of the model on infant colonic fermentation. 

“Our previous in vitro cultivation experiments, as well as literature, indicated that 2’-FL is selectively utilized by only certain types of bifidobacteria and Bacteroides species. This type of modeling with a complex microbiota is a step ahead in our journey to understand the prebiotic mechanisms of 2’-FL,” explains Krista Salli, Scientist at DuPont Nutrition & Biosciences. 

2’-FL is the most prevalent human milk oligosaccharide (HMO) naturally present in human breast milk, making up about 30 percent of all HMOs. HMOs are a structurally diverse group of carbohydrates with known health benefits and are highly abundant in and specific to human breast milk. Moreover, HMOs are resistant to hydrolysis, so once they reach the colon, they act as prebiotics. There, HMOs may promote the growth of beneficial bacteria, such as bifidobacterial species, which are often the predominant species in the microbiota of breastfed infants. 

DuPont researchers had previously tested the EnteroMIX gut simulator on studies on adults, but not yet on infants.In July, DuPont opened a new state-of-the-art probiotics fermentation unit at its Rochester, New York, facility. Construction of the unit was completed in March as part of an overall US$100 million investment to expand the company’s probiotics capacity. 

Results
In this study, 2’-FL generated a more diverse microbiota after the simulations than GOS or lactose did. Breastfed infants harbor less diverse microbiota compared with formula-fed infants, primarily due to a greater proportion of bifidobacteria and lactobacilli in the respective infants.

The study also revealed that microbial diversity has a dual role. Reduced diversity of infant microbiota is linked to various diseases, both in childhood and later in life, such as colic, necrotizing enterocolitis, eczema, asthma, diabetes and autism.

The increase in microbial diversity with 2′-FL compared with GOS and lactose as well as fast- versus slow-fermentation indicates the differential ability of 2′-FL and fast-fermentation have. These can promote the growth of microbes that are metabolically capable of utilizing 2′-FL efficiently in the gut modeling conditions.

“This [study on microbiota obtained from infants] is a great continuation for more than 20 years of expertise using our own preclinical modeling,” notes Dr. Heli Anglenius, Senior Scientist at DuPont Nutrition & Biosciences.

HMOs in infant formula
HMOs are unique in the fact that they promote the growth of certain beneficial bifidobacteria in the infant gut. Such bacteria are known for producing beneficial metabolites and for enhancing gut maturation and shaping the immune responses in a beneficial way. Although breastfeeding is the gold-standard for infant nutrition, there are cases where it is not possible. In such cases, inclusion of HMOs in infant formula can help bring it, nutritionally speaking, a step closer to human milk. 

“At the moment, the majority of the studies have focused on the growth and tolerance of HMOs in infants and in adults as well. Studies investigating the health parameters of the infants and , for example, following of the occurrence of various infectious diseases when consuming infant formula with HMOs in comparison to breastfed infants could be conducted as efficacy studies,” Dr. Anglenius says.

The study revealed that formula-fed infant microbiomes are more diverse than those of breastfed infants.What’s next?
While this study was done under simulated gut conditions, it showed the differences between carbohydrates, especially in the production of microbial metabolites. “These kinds of study approaches can give more understanding on the how HMOs can be utilized by the microbiota with a method that is not invasive, which is important especially in the case of infants,” says Dr. Ratna Mukherjea, Technical Fellow and Global Research and Development HMO at DuPont Nutrition & Biosciences. 

DuPont is currently in the process of replicating the study in a piglet model and will later conduct it in infants, Dr. Anglenius indicates. 

He encourages researchers to build upon the company’s study. “Further studies are needed, also in combination with other HMOs as well as with probiotics, such as with bifidobacteria. These studies would help us fully understand the complex process of fermentation,” he concludes.  

The infant microbiome is a platform that attracts a large amount of research. In September, Assembling a formula-fed infant’s microbiota is still an area that warrants more research, a study pinpointed the key proteins that deliver HMOs to nourish important bifidobacterium, contributing to a healthy infant gut microbiota. This could be used to guide milk formula producers in synthesizing new sugar additives to ensure that formula contains similarly beneficial sugars to breast milk. 

By Anni Schleicher