“Total” folate in blood has usually been measured to evaluate the folate status of pregnant women. However, folate is composed of many metabolites. The main substrate is 5-methyltetrahydrofolate (5-MTHF), with folic acid (FA) representing a very small component as an unmetabolized species in blood. We longitudinally evaluated 5-MTHF, FA and total homocysteine in maternal and cord blood from Japanese pregnant women. Subjects were 146 pregnant women who participated in the Chiba study of Mother and Child Health (C-MACH) prospective cohort study. Sera were obtained in early and late pregnancy, at delivery, and from cord blood. Species levels were measured by isotope-dilution mass spectrometry. Both 5-MTHF and FA levels were lower than reported levels from pregnant women in populations from countries with mandatory FA fortification. As gestational age progressed, serum 5-MTHF levels decreased, whereas serum FA levels were slightly reduced only at delivery compared to early pregnancy. A significant negative association between serum 5-MTHF and total homocysteine was shown at all examined times, but no associations with FA were evident. At delivery, cord 5-MTHF was significantly higher than maternal levels, while FA again showed no significant correlation. These results suggest that 5-MTHF is actively transported to the fetus through placental transporters and may reflect folate status during pregnancy as a physiologically important species.

The prenatal maternal microbiome, including the gut microbiota, has been suggested to influence the incidence of allergies in offspring. Moreover, epidermal barrier dysfunction in early infancy has been attributed to the development of subsequent allergies. We hypothesized that the prenatal microbiome may affect the gut microbiota, acting as an initial trigger to alter immune development in the foetus. The maternal microbial composition may be linked to the prevalence of dermatitis in early infancy (DEI) of the offspring, leading to subsequent allergic symptoms. This study was conducted as part of the Chiba Study of Mother and Child Health (C-MACH) birth cohort that was initiated in 2013; 434 healthy pregnant women at < 13 weeks of gestation were recruited. DEI was assessed for up to 4 months after birth, and allergic symptoms were determined in 10-month-old infants using questionnaires. Other information related to the maternal microbiome was obtained from questionnaires filled out during pregnancy. Stool samples were collected from pregnant women at 12 (n = 59) and 32 weeks (n = 58) of gestation, which were used for gut microbiota analysis using barcoded 16S rRNA gene sequencing. Symptoms of allergy, especially of inherited allergies, show a higher prevalence at 10 months after birth in the DEI group. DEI occurrence was negatively correlated with family size and cat ownership. The diversity of Proteobacteria at 12 weeks of gestation and the relative abundance of Actinobacteria at 32 weeks of gestation in maternal feces were lower at both time points of gestation in the DEI group. In addition, the diversity of Proteobacteria in prenatal feces was negatively correlated with family size at 12 weeks, and with dog ownership at both gestational time points. The composition of the maternal microbiome may influence the risk of allergies in offspring, even before birth. Furthermore, the diversity of Proteobacteria and the relative abundance of Actinobacteria in maternal feces were negatively associated with DEI, which may be associated with the risk of allergy development in infancy. This early trigger may be a good predictor of allergy development during infancy and childhood.

Maintaining optimal one-carbon metabolism (OCM) is essential for health and pregnancy. In this cross-sectional study, folate status was assessed based on 5-methyltetrahydrofolate (5-MTHF) levels, and the association between 5-MTHF and OCM-related metabolites was investigated in 227 female Japanese university students aged 18–25 years. The participants were divided into high and low 5-MTHF groups based on their folate status. Serum samples of the participants were collected while they were fasting, and 18 OCM-related metabolites were measured using stable-isotope dilution liquid chromatography–electrospray tandem mass spectrometry. The association between serum 5-MTHF and OCM-related metabolite concentrations was assessed using Spearman’s rank correlation coefficient. Serum 5-MTHF concentrations were negatively correlated with total homocysteine (tHcy) concentrations and positively correlated with S-adenosylmethionine (SAM) and total cysteine (tCys) concentrations. Serum 5-MTHF concentrations demonstrated a stronger negative correlation with tHcy/tCys than with tHcy alone. The negative correlation between betaine and tHcy concentrations was stronger in the low 5-MTHF group than in the high 5-MTHF group. The 5-MTHF status could be linked to Hcy flux into the transsulfuration pathway via SAM. Therefore, the tHcy/tCys ratio may be a more sensitive indicator of the 5-MTHF status than tHcy alone. Furthermore, a low 5-MTHF status can enhance Hcy metabolism via betaine.

Background: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) sometimes present with stiffness of the cervical muscles. To investigate the pathophysiology of ME/CFS, this observational study compared patients with versus without recovery from ME/CFS through local modulation of the cervical muscles. Methods: Over a period of 11 years, a total of 1226 inpatients with ME/CFS who did not respond to outpatient care were enrolled in this study. All patients received daily cervical muscle physical therapy during hospitalization. Self-rated records documenting the presence or absence of ME/CFS, as well as the representative eight symptoms that frequently accompany it at admission and discharge, were compared. Pupil diameter was also measured to examine autonomic nervous system function involvement. Results: The recovery rate of ME/CFS after local therapy was 55.5%, and did not differ significantly by sex, age strata, and hospitalization period. The recovery rates of the eight symptoms were variable (36.6–86.9%); however, those of ME/CFS in the symptom subpopulations were similar (52.3–55.8%). The recovery rates of all symptoms showed strong associations with that of ME/CFS (p < 0.001). The pupil diameter was more constricted in the ME/CFS-recovered patients than in the ME/CFS-unrecovered patients in the total population and the subpopulations stratified by sex, age, and hospitalization period. Conclusions: There was a strong association between the recovery of ME/CFS and other related whole-body symptoms. The recovery of ME/CFS may be partly linked to amelioration of the autonomic nervous system in the cervical muscles. Trial registration: UMIN000036634. Registered 1 May 2019 - Retrospectively registered.