Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions

PLoS One. 2013 Oct 2;8(10):e76236. doi: 10.1371/journal.pone.0076236. eCollection 2013.

Abstract

Human milk oligosaccharides (HMO) are being studied by different groups exploring a broad range of potential beneficial effects to the breastfed infant. Many of these effects have been attributed to a growth promotion effect on certain gut organisms such as bifidobacteria. Additionally, evidence indicates that HMO are able to directly promote positive changes in gut epithelium and immune responses under certain conditions. This study utilizes a standardized ex vivo murine colon preparation to examine the effects of sialylated, fucosylated and other HMO on gut motor contractions. Only the fucosylated molecules, 2'FL and 3'FL, decreased contractility in a concentration dependent fashion. On the basis of IC50 determinations 3'FL was greater than 2 times more effective than 2'FL. The HMO 3'SL and 6'SL, lacto-N-neotetraose (LNnT), and galactooligosaccharides (GOS) elicited no effects. Lactose was used as a negative control. Fucosylation seems to underlie this functional regulation of gut contractility by oligosaccharides, and L-fucose, while it was also capable of reducing contractility, was substantially less effective than 3'FL and 2'FL. These results suggest that specific HMO are unlikely to be having these effects via bifidogenesis, but though direct action on neuronally dependent gut migrating motor complexes is likely and fucosylation is important in providing this function, we cannot conclusively shown that this is not indirectly mediated. Furthermore they support the possibility that fucosylated sugars and fucose might be useful as therapeutic or preventative adjuncts in disorders of gut motility, and possibly also have beneficial central nervous system effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colon / drug effects*
  • Colon / physiology*
  • Fucose / chemistry
  • Glycosylation
  • In Vitro Techniques
  • Lactose / chemistry
  • Male
  • Mice
  • Milk, Human / chemistry*
  • Muscle Contraction / drug effects*
  • Muscle Contraction / physiology*
  • Oligosaccharides / chemistry
  • Oligosaccharides / pharmacology*

Substances

  • Oligosaccharides
  • Fucose
  • Lactose

Grant support

This study was supported in part by a research grant from Abbott Nutrition who had no involvement in the conduct or execution of the project or the analysis of the data. Support was also provided by the The Giovanni and Concetta Giulietti Family Foundation, St Joseph's Healthcare Hamilton Foundation, NSERC 371513-2009 (PF) and NSERC 371955-2009 (WAK). The funders also had no role in study design or data collection, decision to publish, or preparation of the manuscript, but reviewed it before submission.