Unique study on the role of fatty acids in infants' immune systems

Allergic diseases in children have increased dramatically over the past century. According to the hygiene hypothesis, this increase is due to young children encountering fewer microorganisms early in life, resulting in less training for the immune system. The gut flora in children is established during the first years of life and can provide important stimulation for the immune system.

Short-chain fatty acids (SCFAs) are produced by bacteria in the colon when breaking down carbohydrates and proteins. They serve as fuel for the gut cells and regulate inflammation and immunity. A high level of certain short-chain fatty acids in infants' stools has been linked to a reduced risk of developing allergies in previous studies. Small amounts of short-chain fatty acids can be absorbed from the gut content into the blood and can then be found in the breast milk of nursing women.

"But no one has previously investigated the significance of SCFAs in infants' blood. Different analytical methods are required since the concentration of these fatty acids in the blood is a thousand times lower than the concentration in the gut. With the help of a new highly sensitive methodology, we have now been able to measure these low levels in blood and breast milk," says Ann-Sofie Sandberg, Professor at the Division of Food and Nutrition Science at Chalmers and research leader of the study.

In the current study, researchers analysed the levels of seven different SCFAs in blood samples from 140 mother-infant pairs when the infants were four months old. They also analysed samples of the mothers' breast milk from the same day. The size of the study, and the fact that there are paired samples from mother and child, makes it unique.

Fatty acids are transported from blood to breast milk

Most of the fatty acids were found in lower concentrations in the mother's milk than in her blood, with two exceptions. Butyric acid and caproic acid were both found in concentrations a hundred times higher in the mother's breast milk compared to her blood. Butyric acid, which is used as energy by the cells in the intestinal mucosa, is also anti-inflammatory. The effects of caproic acid are relatively unknown.

"This means that butyric acid must be transported into the breast milk through an active process. We don't know the purpose of this, nor how it is transported. Perhaps butyric acid (and caproic acid) is beneficial for the child's mucous membranes in some way," says Agnes Wold, Professor at the Sahlgrenska Academy.

High levels of SCFAs - lower risk of developing allergies

When the children were 12 months old, they were examined by a specialist in paediatric allergic diseases, who diagnosed the children. At the same occasion, a skin prick test was performed to see if the children had IgE antibodies against food and other common allergens.

The results showed that children with high levels of several different SCFAs in their blood had a lower risk of being sensitized or allergic at one year of age. Sensitization is when the immune system develops a reaction to a substance that is normally harmless – it does not necessarily mean developed allergy.

"Our study provides further support that SCFAs could regulate the immune system and help with the development of physiological tolerance," says Ann-Sofie Sandberg.

Correlations between levels in childrens' and mothers' blood

The study also showed, somewhat surprisingly for the researchers, that the children's blood values could be correlated with the mothers. This means that high levels of SCFAs in the mother's blood could also be seen in the child.

"It was unexpected to find such a strong correlation between the mother's and the child's blood, as four-month-old infants do not have a fully developed gut flora. This leads us to believe that the strong correlation may be due to genetic factors, which would be very interesting to investigate further," says Ann-Sofie Sandberg.

 

More about the study

• In the birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment), 655 children and their families are followed from before birth to 6 years of age.
• Samples are collected from children and parents, and diet and lifestyle factors are mapped through questionnaires. The aim is to understand which factors govern the development of tolerance or allergy and to develop strategies for how allergies can be prevented, for example, through scientifically based dietary advice for pregnant and nursing women.
• Read about the study in eBioMedicine: Short-chain fatty acids (SCFA) in infants’ plasma and corresponding mother's milk and plasma in relation to subsequent sensitisation and atopic disease 
• Writers: Malin Barman, Léna Andrieux, Mia Stråvik, Robert Saalman, Rikard Fristedt, Hardis Rabe, Anna Sandin, Agnes E Wold and Ann-Sofie Sandberg. 

Contact

• Ann-Sofie Sandberg, Professor, Chalmers University of Technology: +46 739 687084 ann-sofie.sandberg@chalmers.se
• Agnes Wold, Professor, University of Gothenburg: +46 733-22 00 47,  agnes.wold@microbio.gu.se