Plenary Session - Life Course Effects of Maternal Diabetes
Gut microbes and metabolic adaptations to pregnancy
Thursday, February 13, 2020
9:45 AM – 10:00 AM
Location: Husky Great Hall (1st Floor Kinnear Centre)
Introduction: Maternal metabolic adaptations occur during pregnancy to support fetal growth, including a decrease in maternal insulin sensitivity and compensatory increase in insulin secretion. Until recently, these changes were thought to be primarily endocrine-mediated. The gut microbiota has emerged as a modulator of host glucose metabolism, but its role in pregnancy-associated metabolic adaptations is unclear. We have shown that maternal gut microbial populations change over the course of pregnancy and in the current study, investigated whether microbiota are necessary for glycemic adaptations to pregnancy.
Methods: Non-pregnant (NP) and pregnant (gestational day 14.5; GD14.5) specific-pathogen free (SPF; NP, n = 10; GD14.5, n=11) and germ-free (GF; NP, n = 6; GD14.5, n = 5) C57BL/6N female mice received an oral glucose tolerance test (oGTT; 3.5g/kg). Mice were sacrificed post-oGTT and blood and pancreatic tissue collected. Serum insulin was measured by ELISA. Pancreatic β-cell mass was quantified by immunohistochemical staining of insulin (abcam, ab7842) in fixed tissue sections. Data were analyzed using a Bonferonni-corrected two-way ANOVA.
Results: Pregnant SPF and GF mice had a lower fasting blood glucose than non-pregnant SPF and GF mice (ppregnancy = 0.0078). Although glucose tolerance was similar between SPF and GF mice at GD14.5, serum insulin increased with pregnancy in SPF mice (p = 0.0095), but not in GF mice, where GF mice have decreased serum insulin overall (pmicrobes = 0.0087). Moreover, GF mice overall, demonstrated lower pancreatic β-cell mass compared to SPF mice (pmicrobes = 0.0265).
Conclusion: Lower serum insulin levels in pregnant GF mice suggests that pregnancy doesn’t impact insulin sensitivity and other insulin-independent glucose-lowering mechanisms may operate in GF pregnant mice. It appears that pancreatic β-cell expansion is hindered in GF mice, suggesting that the gut microbiota may be necessary for increased insulin production during pregnancy. Importantly, this study may inform interventions in maladaptive metabolic states during pregnancy.