Human milk oligosaccharides (HMOs) are complex sugars that occur naturally in human breast milk and provide many beneficial functions. Most formula products lack HMOs or contain only the most abundant HMO, 2′-fucosyllactose; however, benefits of HMOs come from multiple sugars. We therefore developed a mixture of five HMOs (5HMO-Mix) mimicking the natural concentrations of the top five HMOs (5.75 g/L total, comprising 52% 2′-fucosyllactose, 13% 3-fucosyllactose, 26% lacto-N-tetraose, 4% 3′-sialyllactose, and 5% 6′-sialyllactose) representing the groups of neutral, neutral-fucosylated, and sialylated HMOs. We conducted the first multicenter, randomized, controlled, parallel-group clinical study assessing the safety, tolerability, and effect on growth of formula containing the 5HMO-Mix in healthy infants. We enrolled 341 subjects aged ≤14 days; 225 were randomized into groups fed either with infant formula containing 5HMO-Mix (5HMO-Mix) or infant formula without HMOs (IF) for 4 months, with the others exclusively breastfed. There were no differences in weight, length, or head circumference gain between the two formula groups. The 5HMO-Mix was well tolerated, with 5HMO-Mix and breastfed infants producing softer stools at a higher stool frequency than the control formula group. Adverse events were equivalent in all groups. We conclude that the 5HMO-Mix at 5.75 g/L in infant formula is safe and well tolerated by healthy term infants during the first months of life.

Background: Probiotics can modulate the immune system in healthy individuals and may help reduce symptoms related to respiratory infections.Objective:

Breastmilk is the optimal source of infant nutrition, with short-term and long-term health benefits. Some of these benefits are mediated by human milk oligosaccharides (HMOs), a unique group of carbohydrates representing the third most abundant solid component of human milk. We performed the first clinical study on infant formula supplemented with five different HMOs (5HMO-mix), comprising 2′-fucosyllactose, 3-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose and 6′-sialyllactose at a natural total concentration of 5.75 g/L, and here report the analysis of the infant fecal microbiome. We found an increase in the relative abundance of bifidobacteria in the 5HMO-mix cohort compared with the formula-fed control, specifically affecting bifidobacteria that can produce aromatic lactic acids. 5HMO-mix influenced the microbial composition as early as Week 1, and the observed changes persisted to at least Week 16, including a relative decrease in species with opportunistic pathogenic strains down to the level observed in breastfed infants during the first 4 weeks. We further analyzed the functional potential of the microbiome and observed features shared between 5HMO-mix-supplemented and breastfed infants, such as a relative enrichment in mucus and tyrosine degradation, with the latter possibly being linked to the aromatic lactic acids. The 5HMO-mix supplement, therefore, shifts the infant fecal microbiome closer to that of breastfed infants.

To evaluate the administration of Bifidobacterium animalis subsp. lactis, BB-12^® (BB-12) on infant colic in breastfed infants, a double-blind, placebo-controlled randomised study was conducted in Chengdu, China from April 2016 to October 2017 with 192 full-term infants less than 3 months of age and meeting the ROME III criteria for infant colic. After a 1-week run-in the infants were randomly assigned to receive daily BB-12 (1×10⁹ cfu/day) or placebo for 3 weeks. Crying/fussing time were recorded using a 24 h structured diary. The primary endpoint was the proportion of infants achieving a reduction in crying and fussing time of ≥50% from baseline. Parent’s/caregiver’s health related quality of life was measured using a modified PedsQL^™ 2.0 Family Impact Module and immunological biomarkers were evaluated from faecal samples at baseline and after the 21-day intervention. The percentage of infants achieving a reduction in the daily crying/fussing time ≥50% after the 21-day intervention was significantly higher in the infants supplemented with BB-12 (P<0.001). The mean number of crying episodes was significantly reduced in the BB-12 group compared to the placebo group (10.0±3.0 to 5.0±1.87 vs 10.5±2.6 to 7.5±2.8, respectively) (P<0.001) and the mean daily sleep duration was markedly increased from baseline to end of intervention in the BB-12 group compared to the infants in the placebo group (60.7±104.0 vs 31.9±102.7 min/day, respectively) (P<0.001). The faecal levels of human beta defensin 2, cathelicidin, slgA, calprotectin and butyrate were statistically higher in the BB-12 group compared to the placebo group after the 21-day intervention. At the end of the intervention the parent’s/caregiver’s physical, emotional and social functioning scores were significantly higher for the BB-12 group compared to the placebo group (all P<0.05). Supplementation of BB-12 is effective in reducing crying and fussing in infants diagnosed with infant colic.

We investigated the effects of two dosing regimens of two multi-strain probiotic products on the gut microbiota of breastfed infants, including the transfer of the dosed strains and clinical outcomes. In forty-seven dyads, infants were either exposed through maternal intake (MS) of Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, Lacticaseibacillus rhamnosus LGG, and Bifidobacterium longum subsp. infantis Bifin02 from gestational week thirty-three until four weeks after birth (n = 24) or dosed directly (IS) with the same strains except for LA-5 starting within 24 h after birth until day 28 (n = 23). Infant stool samples were collected on day 0, 14, 28, and 42 after birth. Gastrointestinal symptoms were assessed by parents using an electronic diary. Microbiota composition was determined using 16S rRNA sequencing, and strain recovery was analyzed by qPCR. Notably, 100% of the IS infants were colonized with Bifin02 after 14 days as opposed to only 25% of the MS infants. Mean stool frequency was significantly lower in IS infants compared to MS infants and IS infants had softer stools on day 14, 28, and 42. A significantly steeper slope of progression of inconsolable crying and fussing was observed in MS infants compared to IS infants. In conclusion, direct infant seeding induced a faster increase in fecal bifidobacteria abundancy and Bifin02 recovery compared to dosed through the maternal intake.