Can Human Milk Oligosaccharides Prevent NEC?

Can Human Milk Oligosaccharides Prevent NEC?

Any regular reader of this blog will know that human milk and the benefits derived from its consumption is a frequent topic covered. As the evidence continues to mount it is becoming fairly clear that the greater the consumption of mother’s own milk the better the outcomes appear to be with respect to risks of late onset sepsis or BPD as examples. Moving to an exclusive human milk diet has been advocated by some as being the next step in improving outcomes further. While evidence continues to come suggesting that replacement of fortification with a human based instead of a bovine based fortifier may improve outcomes, the largest studies have been retrospective in nature and therefore prone to the usual error that such papers may have.

What is evident though as the science pursues this topic further is that the risk of necrotizing enterocolitis or NEC is not zero even with a human milk diet. Why is that? It might be that some risks for NEC such as intestinal ischemia or extreme prematurity simply are too much to overcome the protective effect of breastmilk. Perhaps though it could be related to something intrinsic in the breastmilk that differs from one mother to another with some producing more protective milk than others.

Secretors vs Non-secretors

When it comes to the constituents of breastmilk, human milk oligosaccharides or HMOs are known to be secreted into breastmilk differently depending on whether a mother has a secretor gene or not. this has been demonstrated recently in HMOs affecting the microbiome in infants Association of Maternal Secretor Status and Human Milk Oligosaccharides With Milk Microbiota: An Observational Pilot Study. HMOs are capable of a few things such as stimulating growth of beneficial microbes and acting as “receptor decoys” for pathogenic bacteria. Previous rat models have also demonstrated their potential to reduce NEC in rat models. Essentially, mothers who have the secretor gene produce more diverse types of HMOs than mothers who are secretor negative.

The Type of HMO May Be the Key To Reducing NEC Wejryd E et al in 2018 published Low Diversity of Human Milk Oligosaccharides is Associated with Necrotising Enterocolitis in Extremely Low Birth Weight Infants This paper was an offshoot of the PROPEL study on the use of prophylactic probiotcs to reduce severe morbidities. Babies were all born between 23 + 0 to 27 +6 weeks and all infants received exclusive breastmilk. All fortification was with a bovine product. Breastmilk samples were obtained from 91 mothers of 106 infants at 2 weeks, 28 days after birth and finally at 36 weeks PMA and the HMO content analyzed.

What came out of the study were a couple very interesting findings. The first is that when analyzing the HMOs present in breastmilk at 2 weeks and comparing those who developed NEC to those who did not there was one significant difference. Lacto-N-difucohexaose I (LNDH I) had a median level of 0 (IQR 0-213) from the milk of those mothers who had infants affected by NEC. There were no differences observed for any other HMOs.

Also of interest was the greater diversity of HMOs present in the breastmilk samples of mothers whose infants did not develop NEC. This was present at all time points.

How Could This Be Useful?

If a broader array of HMOs is associated with less risk of NEC and the presence of LNDH I carries the same association it opens the door to the next phase of this research. Could provision of LNDH I in particular but moreover a wide array of HMOs to mother’s milk reduce the occurrence of NEC? This will need to be tested of course in well designed randomized trials but this type of fortification could be the next step in what we add to human milk to enhance infant outcomes. Given that it may be difficult to determine in short order whether women have these HMOs already a broad based fortification strategy assuming insufficient amounts of HMOs would be best. A quick search on clinicaltrials.gov shows that there are 101 trials in children looking at HMOs at the moment so more information on this topic is certainly on the way. Could HMOs be the magic bullet to help reduce NEC? Just maybe!