The effect of enteral supplementation of a prebiotic mixture of non-human milk galacto-, fructo- and acidic oligosaccharides on intestinal permeability in preterm infants

Randomized placebo-controlled trial in preterm infants admitted to a level III NICU. Infants had gestational age up to 32 weeks and/or birth weight up to 1500 g; 55 infants were randomized to the prebiotic arm and 58 to placebo, with 113 total randomized.

The active regimen was an enteral prebiotic mixture consisting of 80% short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides plus 20% acidic oligosaccharides. It was started between days 3 and 30 of life, given to breast milk or preterm formula in increasing doses up to 1.5 g/kg per day; the mean dose during the first week was 0.73 g/kg per day. The comparator was maltodextrin placebo.

The prebiotic mixture did not improve intestinal permeability in the first week of life. The lactulose-to-mannitol ratio decreased from t0 to t2 in both groups (P<0.001), but there was no additional effect of SC GOS/LC FOS/AOS on the decrease in L/M ratio (effect 0.34, 95% CI 0.22, 0.51; P<0.001). Baseline L/M ratios were 0.21 (0.03-2.16) in the prebiotic group and 0.34 (0.06-1.86) in the placebo group, and lactulose and mannitol concentrations did not differ between groups. Breast milk feeding during the first week was associated with lower intestinal permeability, suggesting any infection-related benefit of the prebiotic mixture would need another mechanism rather than a permeability effect.

Follow-up was short, with intestinal permeability assessed only during the first week of life, so later effects were not evaluated. The trial was single-center and relatively small, and most infants were predominantly breast milk fed, which may limit generalizability and reduce the ability to isolate the intervention effect. Outcomes were based on a surrogate permeability test rather than clinical endpoints such as infection prevention.