Fructooligosaccharide feeding during gestation to pregnant mice provided excessive folic acid decreases maternal and female fetal oxidative stress by increasing intestinal microbe-derived hydrogen gas.

Fructooligosaccharide (FOS) is fermented by intestinal microbes to generate intestinal microbe-derived hydrogen gas (IMDH). Oxidative stress increases during gestation, whereas hydrogen gas has antioxidant effects with therapeutic benefits. We have previously reported that the offspring from a pregnant, excessive folic acid mouse model (PEFAM) had abnormal glucose metabolism after growth. We hypothesized that IMDH by FOS feeding during gestation in PEFAM would suppress maternal and fetal oxidative stress. C57BL/6J mice on day 1 of gestation were divided into 3 groups and dissected at gestational day 18. The control (CONT) diet was AIN-93G containing folic acid 2 mg/kg diet; PEFAM was fed with an excessive folic acid (EFA) diet containing folic acid 40 mg/kg diet, and the EFA-FOS diet was replaced half of the sucrose in the EFA diet. Hydrogen gas concentrations in maternal livers and whole fetuses in EFA-FOS were significantly higher than those in CONT and EFA, respectively (P < .05). Maternal and fetal 8-hydroxy-2'-deoxyguanosine in EFA-FOS were not significantly different from those in the CONT group, whereas those in the EFA group were significantly increased compared with CONT and EFA-FOS (P < .05). In EFA-FOS, expression of protein and mRNA of superoxide dismutase and heme oxygenase 1 in mothers and superoxide dismutase in fetuses were not significantly different from those in CONT, whereas those in EFA were significantly increased (P < .05). The protein expression of Nrf2 in mothers and fetuses were not significantly different between EFA-FOS and CONT. Therefore, FOS feeding to PEFAM during gestation decreases maternal and fetal oxidative stress through IMDH.