The Link between Different Types of Prebiotics in Infant Formula and Infection Rates: A Review

Abstract

Breastfeeding plays a protective role against infections, partially through the prebiotic effect of human milk oligosaccharides (HMOs). Aiming to mimic these beneficial capacities, there is an ongoing search to make infant formula closer to human milk, including by adding oligosaccharides. Over the past two decades, multiple studies have been published on different types of prebiotics and their role in reducing infection rates in infants. This review aims to answer the question of whether there is evidence that the addition of oligosaccharides to infant formula decreases the prevalence of infection, and whether the effect is influenced by the kind of oligosaccharide added. The review of the literature reveals an important heterogeneity, including different types and dosages of prebiotics, different intervention periods and inclusion criteria, etc., making it impossible to formulate a consensus about the efficacy of adding prebiotics to infant formula. We would cautiously suggest that supplementation with galactooligosaccharides (GOSs)/fructooligosaccharides (FOSs) seems to have a beneficial effect on infection rates. For HMOs, more studies about the different types of HMOs are necessary to make any deductions. GOSs alone, inulin, and MOSs (bovine-milk-derived oligosaccharides) do not reduce the incidence of infections. The combination of GOSs and PDX (polydextrose) was found to play a protective role in one study. The evidence of the effect of prebiotics in reducing the use of antibiotics is low. The many lacunas in the direction of study uniformity offer many opportunities for further research.

The Remaining Challenge to Diagnose and Manage Cow’s Milk Allergy: An Opinion Paper to Daily Clinical Practice

“…They bring the gastro-intestinal microbiota composition of these formula-fed infants closer to that of breastfed infants [58][59][60]. Secondary outcomes suggest an immunomodulatory effect, resulting in a decrease in inflammation, infections, and the prescription of antibiotics [61,62]. However, additional benefits on the efficacy of hydrolysates with added probiotics in the management of CMA have not been demonstrated [1].…”

Intestinal microbiota and health in infants and children

“…7 Galacto-oligosaccharides (GOS) and fructooligosaccharides (FOS) are historically the best studied, and supplementation with these seems to have a beneficial effect on infection rates. 8 However, it became recently possible to synthesize some of the ~200 HMOs chemically, via fermentation, and by enzymatic synthesis. Initially, two were added to infant formula: 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT).…”

“…Unfortunately, the designs of these clinical studies are quite different, with different inclusion criteria, duration and amount of administration of oligosaccharides. 6,8 The primary outcomes of these trials focus on safety and tolerance, which have been confirmed. Secondary outcomes suggest a decrease of infections and prescription of antibiotics.…”

“…More studies are needed regarding the optimal combination, duration and dosage of HMOanalogues in infant formula. 6,8 The administration of these HMO-analogues to infant formula are "attractive" because these molecules are identical to some of the oligosaccharides in human milk. However, they remain quite costly and no study has evaluated if there is an additional clinical benefit compared to non-human prebiotics such as FOS and GOS.6,8 One study showed beneficial levels in inflammatory cytokines if 2'-FL was added to infant formula supplemented with GOS.…”

“…Whether HMO-analogues offer a clinical benefit compared to non-human oligosaccharides still needs to be demonstrated. 6,8 While more studies are underway regarding the best oligosaccharides to be added and the duration and dosage of administration, there is enough evidence to recommend the supplementation of infant formula with prebiotic oligosaccharides because "more bifidobacteria bring the GI microbiota composition closer to that of the breastfed infant. "…”