The role of maternal gut hormones in normal pregnancy: fasting plasma active glucagon-like peptide 1 level is a negative predictor of fetal abdomen circumference and maternal weight change

Valsamakis, Georgios; Margeli, Alexandra; Vitoratos, N.; Boutsiadis, Anastassios; Sakkas, Evangelos; Papadimitriou, George; Al-Daghri, Nasser M.; Botsis, D.; Kumar, Sudhesh; Papassotiriou, Ioannis; Creatsas, George; Mastorakos, George

doi:10.1530/eje-10-0047

Cited by 29 publications

(25 citation statements)

References 44 publications

(49 reference statements)

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“…PYY was not altered during pregnancy, agreeing with Valsamakis et al (2010), although values were higher than non-pregnant. Fasted plasma PYY was 63% higher than controls at d10L, demonstrating elevated peripheral concentrations, following earlier peaks in d5L colon tissue.…”

Section: Discussionsupporting

confidence: 72%

Gastrointestinal capacity, gut hormones and appetite change during rat pregnancy and lactation

Johnson¹,

Saffrey²,

Taylor³

2019

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Pregnancy and lactation increase maternal appetite and adiposity, which in humans can lead to long-term body mass retention. Previous rat reproduction studies suggest that appetite-inhibiting gut hormone, peptide-YY (PYY), is elevated, despite hyperphagia also that gastrointestinal size increases. The present study characterised changes in orexigenic (appetite-stimulating) ghrelin and anorexigenic (appetite-inhibiting) PYY and glucagon-like peptide-1 (GLP-1), and gastrointestinal architecture during pregnancy and lactation, in matched fed and fasted plasma and gut tissue samples taken during the dark phase. Enteroendocrine cells were immunolabelled, and gut masses and lengths were measured. Fasted plasma ghrelin reduced during pregnancy: it was lowest by day 18, recovered to control values at parturition, then increased by the end of lactation. Ghrelin-immunoreactive stomach cells and stomach ghrelin concentrations were highest at birth, prior to the onset of lactation-associated hyperphagia. Plasma fed GLP-1 concentrations were elevated during pregnancy, and together with higher colon concentrations of PYY and GLP-1 during early lactation, they were associated with gastrointestinal tissue expansion, not satiety. Body mass increased during lactation, whereas white adipose tissue depots depleted. Extensive gut remodelling coincided with elevated colon concentrations of PYY and GLP-1. Modifications included stomach and caecum expansion, and duodenal, ascending and descending colon circumference increases, all peaking by day 10 of lactation; increased intestinal masses and lengths peaking at lactation day 10 for small intestine and lactation day 25 for large intestine. If these physical tissue increases persist post-partum, they could accelerate future nutrient assimilation and storage in dams, and may contribute to increased obesity risk.

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Section: Discussionsupporting

confidence: 72%

Gastrointestinal capacity, gut hormones and appetite change during rat pregnancy and lactation

Johnson¹,

Saffrey²,

Taylor³

2019

Reproduction

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“…In summary, we have demonstrated alterations in the intestinal microbiome and metabonome in pregnancy that could impair enterohepatic feedback on bile acid synthesis and contribute to the hypercholanemia of pregnancy. Particularly given that the secondary bile acids, DCA and lithocholic acid (LCA), are also potent ligands for the TGR5 receptor at enteroendocrine L cells, the altered microbial modification of bile acids in pregnancy may explain the increasing levels of GLP1 with advancing gestation . Future studies are needed to establish precisely how gestational signals are capable of dramatically impacting the gut microbiome during pregnancy, and whether these gestational signals can be manipulated to enhance beneficial metabolic changes for the pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Microbial Bile Acid Deconjugation and Impaired Ileal Uptake in Pregnancy Repress Intestinal Regulation of Bile Acid Synthesis

et al. 2019

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Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia, and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF) 19/15 protein and mRNA levels, and 7α‐hydroxy‐4‐cholesten‐3‐one. Terminal ileal farnesoid X receptor (FXR)‐mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole‐genome sequencing and ultra‐performance liquid chromatography tandem mass spectrometry were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary CA supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy because of elevated bile salt hydrolase‐producing Bacteroidetes. CA supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. Conclusion: The altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15‐mediated hepatic repression of hepatic bile acid synthesis, resulting in hypercholanemia.

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“…In obese pregnant women, the concentrations of fasting glucose, insulin, and leptin at 16 weeks' gestation resemble those in the third trimester of nonobese, nondiabetic pregnant women (13,14). Moreover, obesity is associated with a higher proportion of the major bacterial phylum Actinobacteria and a lower proportion of the phylum Tenericutes.…”

Section: Discussionmentioning

confidence: 98%

Connections Between the Gut Microbiome and Metabolic Hormones in Early Pregnancy in Overweight and Obese Women

et al. 2016

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Overweight and obese women are at a higher risk for gestational diabetes mellitus. The gut microbiome could modulate metabolic health and may affect insulin resistance and lipid metabolism. The aim of this study was to reveal relationships between gut microbiome composition and circulating metabolic hormones in overweight and obese pregnant women at 16 weeks' gestation. Fecal microbiota profiles from overweight (n = 29) and obese (n = 41) pregnant women were assessed by 16S rRNA sequencing. Fasting metabolic hormone (insulin, C-peptide, glucagon, incretin, and adipokine) concentrations were measured using multiplex ELISA. Metabolic hormone levels as well as microbiome profiles differed between overweight and obese women. Furthermore, changes in some metabolic hormone levels were correlated with alterations in the relative abundance of specific microbes. Adipokine levels were strongly correlated with Ruminococcaceae and Lachnospiraceae, which are dominant families in energy metabolism. Insulin was positively correlated with the genus Collinsella. Gastrointestinal polypeptide was positively correlated with the genus Coprococcus but negatively with family Ruminococcaceae. This study shows novel relationships between gut microbiome composition and the metabolic hormonal environment in overweight and obese pregnant women at 16 weeks' gestation. These results suggest that manipulation of the gut microbiome composition may influence pregnancy metabolism.The increasing prevalence of maternal obesity and its subsequent health outcomes are a significant public health concern and a major challenge for obstetrics practice. In early pregnancy, overweight and obese women are at an increased risk of metabolic complications that affect placental and embryonic development (1). Metabolic adjustments, such as a decline in insulin sensitivity and an increase in nutrient absorption, are necessary to support a healthy pregnancy (2,3); however, these metabolic changes occur on top of preexisting higher levels of insulin resistance in overweight and obese pregnant women, increasing the risk of overt hyperglycemia because of a lack of sufficient insulin secretion to compensate for the increased insulin resistance (3).The potential role of the gut microbiome (the composite of the bacteria present in the gastrointestinal tract) in pregnancy has become the subject of considerable interest. In normal pregnancy, the maternal gut microbiota changes from first to third trimester with a decline in butyrate-producing bacteria and an increase in Bifidobacteria, Proteobacteria, and lactic acid-producing bacteria. Inflammation and weight gain that occurs during pregnancy might be the result of microbe-driven processes to increase energy supply for the fetus (4). These alterations might also be linked with the maternal metabolic profile and thereby contribute to the development of pregnancy complications (5,6) as well as affect the metabolic and immunological health of the offspring (7). In summation, modifications in the metabolic hormone milieu du...

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The role of maternal gut hormones in normal pregnancy: fasting plasma active glucagon-like peptide 1 level is a negative predictor of fetal abdomen circumference and maternal weight change

Cited by 29 publications

References 44 publications

Gastrointestinal capacity, gut hormones and appetite change during rat pregnancy and lactation

Gastrointestinal capacity, gut hormones and appetite change during rat pregnancy and lactation

Enhanced Microbial Bile Acid Deconjugation and Impaired Ileal Uptake in Pregnancy Repress Intestinal Regulation of Bile Acid Synthesis

Connections Between the Gut Microbiome and Metabolic Hormones in Early Pregnancy in Overweight and Obese Women

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