Effects of addition of 2-fucosyllactose to infant formula on growth and specific pathways of utilization by Bifidobacterium in healthy term infants

Abstract

Oligosaccharides in human milk support health via intestinal microbiome. We studied effects of addition of 2-fucosyllactose (2′FL) to the infant formula on infant growth, occurrence of adverse events (AE), and infant microbiome, including expression of microbial genes that metabolize 2′FL. Our hypothesis was that while 2′FL would not affect growth, it would cause changes in microbiome metabolism. In a double-blinded randomized controlled study fashion, the infant formula ± 2′FL or human milk was fed to healthy term infants for 16 weeks. Fecal samples obtained at baseline and week 16 were analyzed for microbial populations, metagenomic species concept (MGS), and genetics of gut metabolic modules (GMMs). There were no effects of addition of 2′FL on growth or AEs. There were no significant differences by feeding group in MGS richness or Shannon diversity at baseline, but formula groups each had significantly greater richness (p < 0.05) and diversity (p < 0.05) after 16 weeks of feeding than the breastfed group. While two glycosyl hydrolase (GH) families (GH42 and GH112) were significantly increased, two other GH families (GH20 and GH2) were significantly decreased in the test formula group compared to the control formula group; although modest, addition of 2′FL resulted in changes in microbiome in the direction of breastfed infants, consistent with internal metabolism of HMOs by Bifidobacterium.

Clinical Studies on the Supplementation of Manufactured Human Milk Oligosaccharides: A Systematic Review

“…In the first group of studies, 2′-FL was added to infant formula alone [ 56 ] or in combination with other prebiotics such as GOS [ 40 ], fructooligosaccharides (FOS) [ 42 , 54 ], or a mixture of fermented GOS and FOS including 3′-GL [ 47 ]. It has also been combined with probiotic bacteria such as Bifidobacterium animalis ssp.…”

“…Growth was measured in all but one of the infant studies [ 59 ]. It was the primary outcome in 13 of 16 infant studies [ 39 , 40 , 43 , 46 , 47 , 49 , 50 , 51 , 52 , 54 , 56 , 57 , 58 ]. It was mostly assessed in terms of non-inferior weight gain per day in intervention groups compared to control formulas and breastfed groups throughout the intervention period.…”

“…It was mostly assessed in terms of non-inferior weight gain per day in intervention groups compared to control formulas and breastfed groups throughout the intervention period. Other anthropometric parameters measured included length, head circumference, weight, body mass index, and interval gains, which were assessed either by comparison with reference groups or WHO child growth standards [ 39 , 40 , 42 , 43 , 44 , 46 , 47 , 49 , 50 , 51 , 52 , 54 , 57 , 58 , 59 ]. All studies reported age-appropriate growth following HMO supplementation and the absence of significant growth differences between intervention groups and controls ( Table 2 and Table 3 ).…”

“…The most frequently studied HMO is 2 -FL, which has been investigated in 22 clinical trials (Table 6). IBS symptoms -No effect on gut microbiome composition [66] Follow-up analysis of [65] -----Effect on microbiome composition in fecal and mucosal colonic biopsies samples -Effect on fecal and plasma biomarkers [67] Adults with IBS (n = 317) Open-label, multicenter, single-arm trial In the first group of studies, 2 -FL was added to infant formula alone [56] or in combination with other prebiotics such as GOS [40], fructooligosaccharides (FOS) [42,54], or a mixture of fermented GOS and FOS including 3 -GL [47]. It has also been combined with probiotic bacteria such as Bifidobacterium animalis ssp.…”

Select human milk oligosaccharide supplementation in post‐weanling rats affects metabolism and gut microbiota into adulthood

“…Formula feeding tends to result in lower abundance of Bifidobacterium possibly because of the lack of the HMO component [12]. Infant formula fortified with HMOs, specifically 2'-O-fucosyllactose (2'FL), can create a gut microbiota profile with a higher abundance of Bifidobacterium similar to human milk-fed infants [13][14][15]. The most abundant HMO is 2'FL, but it should be noted that a subset of the population does not synthesize 2'FL; thus other HMOs also play an important role in the beneficial effects of breastfeeding [16][17][18].…”