Bifidobacterium adolescentis SBT2786 Improves Sleep Quality in Japanese Adults with Relatively High Levels of Stress: A Randomized, Double-Blind, Placebo-Controlled Study.

Sleep disorders associated with lifestyle changes and unhealthy habits are major public health concerns. Our previous study showed that Bifidobacterium adolescentis SBT2786 has a potent sleep-promoting effect on fruit flies. Fruit flies share many similarities with mammals, making them suitable model organisms for studying sleep. Thus, in the present study, we conducted a randomized, double-blind, placebo-controlled clinical trial to test whether SBT2786 has sleep-enhancing effects in humans. In this study, 61 participants in the SBT2786 group and 65 participants in the placebo group were analyzed. The results showed that SBT2786 increased sleep time; however, it predominantly increased light sleep and did not improve subjective sleep quality. Interestingly, mood improvement was observed. A subgroup analysis was conducted on participants with high stress levels, and results showed that these participants experienced an increase in sleep duration and an improvement in sleepiness upon waking up and reported feeling well-rested during the day. We concluded that SBT2786 may improve sleep quality, particularly in individuals experiencing high levels of stress, and that SBT2786 can be used as a dietary supplement to improve sleep and mood.

Behavioral screening of sleep-promoting effects of human intestinal and food-associated bacteria on Drosophila melanogaster.

Commensal microbes influence various aspects of vertebrate and invertebrate brain function. We previously reported that Lactiplantibacillus plantarum SBT2227 promotes sleep in the fruit fly, Drosophila melanogaster. However, how widely the sleep-promoting effects are conserved in gut bacterial species remains unknown. In this study, we orally administered human intestinal and food-associated bacterial species (39 in total) to flies and investigated their effects on sleep. Six species of bacteria were found to have significant sleep-promoting effects. Of these, we further investigated Bifidobacterium adolescentis, which had the greatest sleep-promoting effect, and found that the strength of the sleep effect varied among strains of the same bacterial species. The B. adolescentis strains BA2786 and BA003 showed strong and weak effects on sleep, respectively. Transcriptome characteristics compared between the heads of flies treated with BA2786 or BA003 revealed that the gene expression of the insulin-like receptor (InR) was increased in BA2786-fed flies. Furthermore, a heterozygous mutation in InR suppressed the sleep-promoting effect of BA2786. These results suggest that orally administered sleep-promoting bacteria (at least BA2786), may act on insulin signaling to modulate brain function for sleep.

Comparison of Vitamin D and 25-Hydroxyvitamin D Concentrations in Human Breast Milk between 1989 and 2016-2017.

BACKGROUND: Breast milk is considered the optimal source of nutrition during infancy. Although the vitamin D concentration in human breast milk is generally considered poor for infants, vitamin D in breast milk is an important source for exclusively breastfed infants. Increases in vitamin D insufficiency and deficiency in lactating mothers may reduce vitamin D concentrations in breast milk. This study aimed to compare vitamin D and 25-hydroxyvitamin D (25OHD) concentrations in breast milk collected in 1989 and 2016-2017 and simultaneously analyze them with liquid chromatography-tandem mass spectrometry (LC-MS/MS); the association between the lifestyle of recent lactating mothers (2016-2017) and vitamin D status in human breast milk was also evaluated. METHOD: Lactating mothers were recruited from three regions of Japan in 1989 (n = 72) and 2016-2017 (n = 90), and milk from 3-4 months was collected in summer and winter. The samples were strictly sealed and stored at -80℃ until measurement. Breast milk vitamin D and 25OHD concentrations were analyzed by LC-MS/MS. Vitamin D intake, sun exposure, and sunscreen use of the lactating mothers in 2016-2017 were assessed. RESULTS: Both vitamin D and 25OHD concentrations in breast milk were higher in the summer regardless of the survey year. Significantly lower vitamin D and 25OHD concentrations were observed in 2016-2017 compared with 1989 in summer, but no survey year difference was observed in winter. The stepwise multiple regression analyses identified season, daily outdoor activity, and suntan in the last 12 months as independent factors associated with vitamin D3 concentrations. CONCLUSION: The results suggest that low vitamin D status in recent lactating mothers may have decreased vitamin D and 25OHD concentrations in breast milk compared with the 1980s. These results are helpful for developing public health strategies to improve vitamin D status in lactating mothers and infants.

Cohort profile: Japanese human milk study, a prospective birth cohort: baseline data for lactating women, infants and human milk macronutrients.

PURPOSE: The Japanese Human Milk Study, a longitudinal prospective cohort study, was set up to clarify how maternal health, nutritional status, lifestyle and sociodemographic and economic factors affect breastfeeding practices and human milk composition. This would eventually determine factors affecting the growth and development of infants and children. PARTICIPANTS: A total of 1210 Japanese lactating women who satisfied the inclusion criteria, were invited across the country at various participating sites, between 2014 and 2019. Finally a total of 1122 women were enrolled in this study. FINDINGS TO DATE: Among 1122 eligible participants, mean age at delivery was 31.2 (SD 4.4) years and mean prepregnancy BMI was 20.8 (SD 2.7). Among these women, 35% were previously nulliparous and 77.7% had college, university or higher education. The mean gestational period was 39.0 (SD 1.3) weeks. Caesarean section was reported among 11.9%; mean infant birth weight was 3082 (SD 360) g. Of the infants, 53.7% were male. Overall, our participants appeared to be healthier than the general population in Japan. Analyses of the 1079 eligible human milk samples obtained at the first and second months postpartum showed the following composition: carbohydrate, 8.13 (SD 0.32) g/100 mL; fat, 3.77 (SD 1.29) g/100 mL; and crude protein, 1.20 (SD 0.23) g/100 mL. We also analysed osteopontin, fatty acid, vitamin D and phospholipid levels in limited subcohorts of the samples. FUTURE PLANS: Follow-up surveys will be conducted to obtain milk samples every 2 months for 12 months and to investigate mother and child health until the children reach 5 years of age. These will be completed in 2024. We plan to longitudinally analyse the composition of macronutrients and various bioactive factors in human milk and investigate the lifestyle and environmental factors that influence breastfeeding practices, maternal and child health, and child development. TRIAL REGISTRATION NUMBER: UMIN000015494; pre-results.

Maternal Health and Nutrition Status, Human Milk Composition, and Growth and Development of Infants and Children: A Prospective Japanese Human Milk Study Protocol.

It is unknown whether maternal health and nutrition are related to human milk composition or growth and development of infants and children. Here, we describe a protocol for a prospective five-year cohort study to clarify (i) how maternal health and nutrition, socioeconomic factors, and lifestyles affect human milk composition, and (ii) whether these are associated with growth and development of infants and children. In our study, we recruited 1210 Japanese mothers with singleton pregnancies from 73 obstetrics clinics and hospitals across Japan, between 2014 and 2019. We will measure the following: health information regarding maternal-child dyads using a self-administered questionnaire, maternal nutrition during breastfeeding using a Brief self-administrated Diet History Questionnaire, the development of infants and children using the Kinder Infant Development Scale, and the stress related to child rearing using the Mother's Child Care Stress Scale. Simultaneously, we will collect human milk every 2 months during the first year after birth to measure its composition and levels of macronutrients. This study will generate useful data to investigate whether health status, nutritional status, lifestyle, and socioeconomic factors affect human milk composition and the growth and development of infants and children.

Microwave treatment of breast milk for prevention of cytomegalovirus infection.

BACKGROUND: Breast milk (BM) is the best nutrition for very preterm infants (VPI), except when provided by human cytomegalovirus (HCMV)-seropositive mothers. Given that VPI are at high risk of developing a sepsis-like syndrome or cholestasis, methods for prevention of HCMV infection via BM have been investigated. Although Holder pasteurization (HP) is the gold standard, HP needs special instruments. Microwave (MW) is available anywhere, therefore, we performed this study to determine whether MW can be used for HCMV prevention. METHODS: Human cytomegalovirus Towne strain was added to formula, followed by heating procedure using HP or MW (at 500 W for 20, 30, 40, or 60 s). HFL-III cells were seeded in culture dishes. Aliquots of HCMV-milk samples after heating were inoculated onto susceptible cell monolayers. The number of plaques was counted to determine the viral titer. The determination of HCMV-DNA copies was also performed. RESULTS: Addition of HCMV for a viral load of 5.0 × 103 plaque-forming units (p.f.u.)/mL achieved 772 p.f.u./mL at baseline, with a decrease to 257 p.f.u./mL after MW radiation for 20 s. No plaque was detected after HP or MW for 30, 40, and 60 s. The temperature of the breast milk reached 60°C after MW radiation for 40 s. The number of HCMV-DNA copies did not change with MW. CONCLUSIONS: Microwave at 500 W for 40 s can be used as a prevention strategy for HCMV transmission. Further research including the loss of bioactive properties in BM is required prior to clinical application.

Osteopontin Levels in Human Milk Vary Across Countries and Within Lactation Period: Data From a Multicenter Study.

OBJECTIVES: Osteopontin (OPN) is a multifunctional protein expressed in many cell types, tissues and body fluids with the highest concentrations found in milk; significantly higher in human than in bovine milk. Intervention studies have indicated beneficial effects of supplementing infant formula with bovine OPN. In this multicenter study, we determined the OPN content in human milk samples from 629 Chinese, Danish, Japanese and Korean mothers. METHODS: At each study site, milk samples were collected and analyzed for OPN and protein concentration using ELISA and infrared spectroscopy, respectively. RESULTS: A total of 829 milk samples from 629 women were included. When delivering the first sample, mean maternal age was 31.4 years (SD 4.0), and median infant age was 13.4 weeks (interquartile range 4.6-17.9). The median OPN concentration varied across sites; from 99.7 mg/L in Danish, 185.0 mg/L in Japanese, 216.2 mg/L in Korean to 266.2 mg/L in Chinese mothers (P < 0.001), corresponding to 1.3%, 2.4%, 1.8% and 2.7% of the total protein content (OPN/protein%) (P < 0.05), respectively. Based on 75 Chinese and 33 Japanese mothers delivering more than 1 sample, multilevel (mixed model) linear regression analysis showed a decrease in OPN concentration with infant age (ß = (-11.3), 95% confidence interval (CI) = (-13.9) to (-8.8) and ß = (-2.1), 95% CI = (-3.2) to (-0.9), respectively). CONCLUSIONS: In this large multicenter study, we observed statistically significant differences in the OPN concentration and the OPN/protein% in human milk samples between countries. Based on mothers delivering more than 1 sample, a significant decrease within the lactation period was observed.