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High ambient temperature exposure during late gestation disrupts glycolipid metabolism and hepatic mitochondrial function tightly related to gut microbial dysbiosis in pregnant mice.

ABSTRACT: As global warming intensifies, emerging evidence has demonstrated high ambient temperature during pregnancy negatively affects maternal physiology with compromised pregnant outcomes; however, little is known about the roles of gut microbiota and its underlying mechanisms in this process. Here, for the first time, we explored the potential mechanisms of gut microbiota involved in the disrupted glycolipid metabolism via hepatic mitochondrial function. Our results indicate heat stress (HS) reduces fat and protein contents and serum levels of insulin and triglyceride (TG), while increases that of non-esterified fatty acid (NEFA), β-hydroxybutyric acid (B-HBA), creatinine and blood urea nitrogen (BUN) (P < 0.05). Additionally, HS downregulates both mitochondrial genes (mtDNA) and nuclear encoding mitochondrial functional genes with increasing serum levels of malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) (P < 0.05). Regarding microbial response, HS boosts serum levels of lipopolysaccharide (LPS) (P < 0.05) and alters β-diversity (ANOSIM, P < 0.01), increasing the proportions of Escherichia-Shigella, Acinetobacter and Klebsiella (q < 0.05), while reducing that of Ruminiclostridium, Blautia, Lachnospiraceae_NK4A136_group, Clostridium VadinBB60 and Muribaculaceae (q < 0.05). PICRUSt analysis predicts that HS upregulates 11 KEGG pathways, mainly including bile secretion and bacterial invasion of epithelial cells. The collective results suggest that microbial dysbiosis due to late gestational HS has strong associations with damaged hepatic mitochondrial function and disrupted metabolic profiles.

SUBMITTER: He J

PROVIDER: S-EPMC8449678 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPhenylalanine is an indispensable amino acid and, via tyrosine, is the precursor for the neurotransmitters dopamine, norepinephrine, and epinephrine. Currently, dietary requirements for phenylalanine during pregnancy are unknown.ObjectivesThis study's aim was to determine phenylalanine requirements (in the presence of excess tyrosine) during early and late gestation using direct amino acid oxidation (DAAO; with l-[1-13C]phenylalanine) and indicator amino acid oxidation (IAAO; with l-[1-13C]leucine).MethodsTwenty-three healthy women (age: 30.4 ± 3.1 y, mean ± SD) were studied at a range of phenylalanine intakes (5.5-30.5 mg · kg-1 · d-1 in early and late pregnancy using DAAO, and 2.5-30.5 mg · kg-1 · d-1 in late pregnancy using IAAO) for a total of 76 study days. Test intakes were provided as 8 isocaloric and isonitrogenous meals with 1.5 g · kg-1 · d-1 protein and energy at 1.7 times the measured resting energy expenditure. Breath samples were analyzed on an isotope ratio mass spectrometer for 13C enrichment. Phenylalanine requirement was determined using a 2-phase linear regression crossover model to identify a breakpoint in 13CO2 production (representing the mean requirement) in response to phenylalanine intakes.ResultsPhenylalanine requirement during early pregnancy was determined to be 15 mg · kg-1 · d-1 (95% CI: 10.4, 19.9 mg · kg-1 · d-1); during late pregnancy, it was determined to be 21 mg · kg-1 · d-1 by DAAO (95% CI: 17.4, 24.7 mg · kg-1 · d-1) and IAAO (95% CI: 10.5, 32.2 mg · kg-1 · d-1).ConclusionsOur results suggest a higher requirement (40%) for phenylalanine during late pregnancy than during early pregnancy. Moreover, the early pregnancy requirements are higher than the previous adult male requirement (9.1 mg · kg-1 · d-1; 95% CI: 4.6, 13.6 mg · kg-1 · d-1), although the 95% CIs overlap. Both DAAO and IAAO methods provided similar breakpoints in late pregnancy, showing that the DAAO method was appropriate even though low phenylalanine intakes could not be tested. These results have potential implications for gestation stage-specific dietary phenylalanine recommendations in future.This trial was registered at clinicaltrials.gov as NCT02669381.

Project description:BackgroundPhenylalanine and tyrosine (referred to as total aromatic amino acids; TAAs) are essential for protein synthesis, and are precursors for important catecholamines. Current estimated average requirement (EAR) recommendations for TAA during pregnancy are 36 mg·kg-1·d-1, and has not been experimentally determined.ObjectivesThe aim was to determine TAA requirements (dietary phenylalanine in the absence of tyrosine) during early and late gestation using the indicator amino acid oxidation (IAAO, with L-[1-13C]leucine) technique.MethodsNineteen healthy pregnant women (age 22-38 y) were studied at a range of phenylalanine intakes (5 to 100 mg·kg-1·d-1) in early (13-19 wk) and/or late (33-39 wk) pregnancy for a total of 51 study days. Graded test intakes were provided as 8 hourly isonitrogenous and isocaloric meals. Breath samples were collected for 13C enrichment analysis on an isotope ratio mass spectrometer. A plasma sample was collected and analyzed for phenylalanine and tyrosine concentrations on an amino acid analyzer. The TAA requirement in early and late pregnancy was calculated using 2-phase linear regression crossover analysis that identified breakpoints in 13CO2 production (the requirement) in response to phenylalanine intakes.ResultsTAA requirement during early pregnancy was 44 mg·kg-1·d-1 (95% CI: 28.3, 58.8) and during late pregnancy was 50 mg·kg-1·d-1 (95% CI: 36.1, 63.1). In early and late pregnancy, plasma phenylalanine and tyrosine concentrations rose linearly in response to graded phenylalanine intakes.ConclusionsOur results suggest that the current EAR of 36 mg·kg-1·d-1 for TAAs is underestimated. When compared with results previously determined in nonpregnant adults, early pregnancy requirements were similar (43 compared with 44 mg·kg-1·d-1, respectively). During late pregnancy, a 14% higher TAA requirement was observed when compared with early pregnancy. The results from this study have potential implications for creating gestation stage-specific TAA recommendations.

Project description:BACKGROUND:Evidence suggests the possible impact of ambient high temperature on fetal growth and birth outcomes. However, little is known about the relative impact of exposure to heat and cold and the possible vulnerable window during pregnancy. METHODS:Data on a total of 237,585 pregnant women from January 1st, 2001 to December 31st, 2010 were acquired from the Queensland Health, Australia. Daily data on meteorological factors, including ambient temperature, relative humidity, barometric pressure, and air pollutants, such as PM10, SO2, NO2, and O3, were obtained from relevant government agencies. This study was to examine the associations of maternal exposure to ambient temperature (high and low temperatures, in early vs. late pregnancy) with the duration of gestation and birth weight. RESULTS:A J-shaped association between minimum temperature at conception and duration of gestation was observed after adjusting for seasonality and other confounders. Compared to women who were exposed to the minimum temperature of 15-20?°C in the first gestational week, exposure to the minimum temperature of >?20?°C significantly increased the duration of gestation by 0.029?weeks (95% CI: 0.008, 0.049). A cumulative effect was found when exposure across the first four weeks was examined. There was an inverted U-shaped relationship between minimum temperature at delivery and the duration of gestation. Compared to women exposed to 15-20?°C, exposure to minimum temperature of >?20?°C and???10?°C was associated with a shortened gestation by 0.030?weeks (95% CI: -0.052, -?0.008) and 0.018?weeks (95% CI: -0.057, -?0.004), respectively. By contrast, an inverse relationship between maximum temperature and birth weight was observed. Compared to exposure to the maximum temperature of >?30?°C in the last week of pregnancy, maternal exposure to 20-25?°C and?<?20?°C significantly increased birth weight by 0.011?kg (95% CI: 0.008, 0.018) and 0.018?kg (95% CI: 0.010, 0.031), respectively. Similarly, a mild cumulative effect was observed when maximum temperature exposure across the four weeks before delivery was evaluated. CONCLUSIONS:The finding emphasized the importance of keeping an optimal temperature range during pregnancy for reducing the risk of preterm birth and low birthweight.

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High ambient temperature exposure during late gestation disrupts glycolipid metabolism and hepatic mitochondrial function tightly related to gut microbial dysbiosis in pregnant mice.

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