Fructooligosaccharides (FOS) can selectively stimulate the growth of bifidobacteria. Here, we investigated the effect of maternal FOS ingestion on maternal and neonatal gut bifidobacteria. In a randomized, double-blind, placebo-controlled study, we administered 8 g/day of FOS or sucrose to 84 women from the 26th week of gestation to one month after delivery. The bifidobacteria count was detected using quantitative PCR in maternal (26 and 36 weeks of gestation) and neonatal (one month after delivery) stools. Maternal stool frequency was recorded from 24 to 36 weeks of gestation. The number of fecal Bifidobacterium spp. and Bifidobacterium longum in the FOS group was significantly higher than that in the placebo group at 36 weeks of gestation (2.7 × 10¹⁰/g vs. 1.1 × 10¹⁰/g and 2.3 × 10¹⁰/g vs. 9.7 × 10⁹/g). In their neonates, these numbers did not differ between the groups. Also, stool frequency in the FOS group was slightly higher than that in the placebo group two weeks after the intervention (1.0 vs. 0.8 times/day), suggesting a potential constipation alleviation effect. In conclusion, the maternal FOS ingestion showed a bifidogenic effect in pregnant women but not in their neonates.

We determined whether a potential probiotic bacterium, Bifidobacterium bifidum OLB6378 (BB6378), exerts beneficial effects on the mucosal immune system in a mouse intestinal explant model. The addition of heat‐inactivated BB6378 to intestinal explants prepared from embryonic day 18 BALB/c mice increased the expression of polymeric immunoglobulin receptor (pIgR) mRNA by two‐ to fivefold. These effects were observed on ileal and colonic explants but not on jejunal explants, suggesting that the BB6378‐induced pIgR upregulation is site‐specific within the mouse intestine. The upregulation of pIgR protein expression in colonic explants was also detected after 24 h of culture. The results of DNA microarray analysis of ileal and colonic samples indicated that BB6378 increased the gene expression of interleukin (IL)‐1α and IL‐1β, and IL‐1α content in colonic explants was significantly increased after 20 h of culture with BB6378. We then examined the involvement of endogenously induced IL‐1α in pIgR mRNA upregulation by using IL‐1α knockout (KO) mice. Contrary to our expectations, pIgR mRNA expression was equally upregulated by BB6378 in colonic explants from BALB/c and IL‐1α KO mice. Conversely, we examined the involvement of Toll‐like receptors in pIgR mRNA upregulation by using MyD88 KO mice. The upregulation of pIgR was completely suppressed in the explants derived from MyD88 KO mice. Taken together, we conclude that in a mouse intestinal explant model, the heat‐inactivated potential probiotic BB6378 increases intestinal pIgR expression in a site‐specific manner and that the upregulation of pIgR could be explained by a direct microbial effect on the epithelium via Toll‐like receptors.

The consumption of probiotics by pregnant and lactating women may prevent the onset of allergic disorders in their children by increasing the concentrations of immunoactive agents such as cytokines in breast milk. Prebiotics such as fructo-oligosaccharides (FOS) increase the number of beneficial organisms such as bifidobacteria. Thus, prebiotics may have an effect similar to that of probiotics. The objective of the present study was to carry out a comprehensive analysis of mRNA expression in human milk cells to identify changes in the concentrations of cytokines in breast milk after the consumption of FOS (4 g × 2 times/d) by pregnant and lactating women. The microarray analysis of human milk cells demonstrated that the expression levels of five genes in colostrum samples and fourteen genes in 1-month breast milk samples differed more than 3-fold between the FOS and control groups (sucrose group). The mRNA expression level of IL-27, a cytokine associated with immunoregulatory function, was significantly higher in 1-month breast milk samples obtained from the FOS group than in those obtained from the control group. In addition, the protein concentrations of IL-27 in colostrum and 1-month breast milk samples were significantly higher in the FOS group than in the control group. In conclusion, the consumption of FOS by pregnant and lactating women increases the production of IL-27 in breast milk. Future studies will address the association of this phenomenon with the onset of allergic disorders in children.

Human milk oligosaccharides (HMOs) have been positively associated with child neurodevelopment in some cohort studies. However, there is a lack of consistency in the association between HMOs and benefits to infants’ brains. Moreover, the quantification methods for HMOs have not yet been standardized. In this study, we developed a quantification method for evaluating eight HMOs (2′‐fucosyllactose [2′‐FL], 3′‐fucosyllactose [3′‐FL], 3′‐sialyllactose [3′‐SL], 6′‐sialyllactose [6′‐SL], lactosialyltetrasaccharide a [LSTa], lactosialyltetrasaccharide b [LSTb], lactosialyltetrasaccharide c [LSTc], and disialyllacto‐N‐tetraose [DSLNT]) in breast milk. After validating the method, we applied it to 1‐month breast milk samples ( n = 150) from the Tohoku Medical Megabank Project Birth and Three‐Generation Cohort Study to assess HMO profiles in breast milk and their possible association with changes in head circumference z‐score (ΔHCZ) and neurodevelopmental scores of children (as measured by the Ages and Stages Questionnaire, Third Edition). The validation demonstrated that the method had relative standard deviation ≤ 12.7% of precision and 79.5–110.9% of accuracy. Using this method, eight HMO levels (2′‐FL, 0–4.74 mg/mL; 3′‐FL, 0.02–1.52 mg/mL; 3′‐SL, 0.07–0.32 mg/mL; 6′‐SL, 0.01–0.70 mg/mL; LSTa, 0.002–0.043 mg/mL; LSTb, 0.02–0.31 mg/mL; LSTc, 0.001–0.47 mg/mL; and DSLNT, 0.09–0.71 mg/mL [min–max, all participants]) and the ratio of low secretors (16.0%) in the Japanese cohort were obtained. The obtained HMO levels in breast milk were subjected to multivariate analysis to screen for HMOs showing a positive association with ΔHCZ and neurodevelopmental scores. The results proposed that ΔHCZ was positively associated with LSTb and 2′‐FL levels, whereas neurodevelopmental scores were positively associated with 2′‐FL levels (among all participants) and 3′‐SL and DSLNT levels (among secretor participants). This study showed that the developed method provides HMO profiles in Japanese breast milk, as well as additional information on the associations between specific HMOs and neurodevelopment, reinforcing the sum of evidence for the role of HMOs in the brain.

Background: Recently, more attention has been paid to behavioral problems in children. However, for the most part, risk factors for these problems have yet to be determined. Objective: The current prebirth cohort study investigated the relationship between maternal calcium consumption during pregnancy and behavioral problems in five-year-old Japanese children. Methods: Subjects were 1199 mother-child pairs. Dietary intake during the preceding month was assessed using a self-administered diet history questionnaire. Emotional problems, conduct problems, hyperactivity problems, and peer problems were assessed using the Strengths and Difficulties Questionnaire. Logistic regression analysis was conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Compared with the lowest quartile of maternal calcium intake, the highest was significantly associated with decreased risk of childhood emotional problems: the adjusted OR (95% CIs) was 0.46 (0.27–0.79, P for trend = 0.01). Higher maternal calcium intake during pregnancy was also independently associated with decreased risk of childhood hyperactivity problems; the adjusted ORs (95% CIs) in the first, second, third, and fourth quartiles of maternal calcium intake during pregnancy were 1 (reference), 0.52 (0.31–0.84), 0.58 (0.35–0.93), and 0.60 (0.37–0.97), respectively (P for trend = 0.046). No such inverse associations were observed for childhood conduct problems or peer problems; the adjusted ORs (95% CIs) in the highest quartile of maternal calcium intake were 0.97 (0.64–1.47) for conduct problems and 1.11 (0.61–2.01) for peer problems. Conclusions: Maternal calcium intake during pregnancy may decrease the risk of childhood emotional and hyperactivity problems.