Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions

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.

Figure 1. Effects of lactose on peak pressures in colon motility experiments.

Lack of effect of β-Lactose (1mg/mL) on peak preasures of migrating motor complexes in 'before and after' experiments (n=6). ns=not significant.

Figure 2. Concentration response curves for effects of fucosylated HMO.

Effects of 3’FL (A), 2’FL (B) and L-Fucose (C) on peak pressure. Inset table indicates the number of points fitted to the curve and IC₅₀ values. * p values <0.05.

Figure 3. Effects of 0.5 mg/mL intraluminal 2’FL on colon motility.

Heat maps derived from black/white spatio-temporal video recordings of colon motility. (A) Shows regular migrating motor complexes (MMCs) during control recording. (B) Addition of 2’FL to the lumen decreased both the slope (MMC velocity) of the valleys and MMC frequency. (C, D) Summary statistics of before and after experiments showing that 2’FL significantly reduced both MMC velocity (C) and frequency (D).

Figure 4. Before and after results of effects of non-fucosylated HMO.

Lack of effects of 3’ SL (A), 6’SL (B), LNnT (C) and GOS (D). n=>6/oligosaccharide tested. ns= not significant. Concentrations of all HMO shown at 1mg/mL for comparison purposes. None had any effect on motility up to 5mg/mL.