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1H-NMR based metabolomics on plasma shows that changes in Microbiota Correlate with Hyperglycemia in Gestational Diabetes

Gestational diabetes mellitus is a generally temporary form of diabetes that occurs in pregnant women. In this condition, hormones produced during pregnancy cause the body to lose its ability to use insulin, a peptide hormone that helps drive carbohydrate-derived glucose into cells to be used for energy. Common hormones during pregnancy that have been implicated in this include estrogen, cortisol, and lactogen.

The prevalence of gestational diabetes has risen dramatically in recent years, but the reasons for this increase have not been fully identified. In addition, the pathogenesis of gestational diabetes is not well understood.

The Link Between Gut Microbiota and Gestational Diabetes

Based on previous research, the investigators of a new metabolomics study suggest that the gut microbiota in pregnant women could be a source of gestational diabetes biomarkers. In the study, researchers from China examined the mediation effect of gut microbiota changes on circulating metabolites in women with and without gestational diabetes.

The study included 40 pregnant women with half of whom had gestational diabetes and entered a hospital in China. Overnight fasting feces samples were obtained to study and compare changes in the gut microbiome between patients with and without gestational diabetes.

Researchers used the Bruker 600 MHz AVANCE III nuclear magnetic resonance (NMR) spectrometer to perform 1H-NMR based untargeted metabolomics analysis on plasma samples.

Observed Microbiota Changes in Gestational Diabetes

The researchers were able to discriminate fecal microbiota of patients with gestational diabetes versus non diabetic mellitus (control group) by using PCA and OPLS-DA. According to the researchers, this finding indicates the existence of compositional changes along the vector of high-blood sugar, or hyperglycemia. Compared to the non-diabetes control group, there were significant changes in alpha diversity (p=0.039) and beta diversity (p=3.41 x 10-6) in the fecal microbiota of women with gestational diabetes

Additionally, the researchers found 98 members of fecal microbiota that contributed to the associations between fecal microbiota changes and the incidence of hyperglycemia. While Blautia was decreased in women with gestational diabetes, the following bacterial genera were increased in these women:

  • Phascolarctobacterium
  • Alistipes
  • Parabacteroides
  • Eubacterium coprostanoligenes_group
  • Oscillibacter
  • Paraprevotella
  • Ruminococcaceae NK4A214_group

A population of Firmicutes in the microbiota correlated with changes in the plasma metabolome that were associated with gestational diabetes. In total, there were 15 genera in this population, all of which positively correlated with each other.

Another analysis of the 1H-NMR plasma spectrashowed that 5 small molecule metabolites contributed to changes in the microbiota of patients with gestational diabetes. These plasma metabolites included glycerol, lactic acid, proline, galactitol, and methylmalonic acid. Lower levels of methylmalonic acid were observed in women with gestational diabetes relative to the non-diabetes controls. In addition, 4 out of the 5 metabolites were associated with hyperglycemia. These hyperglycemia-associated metabolites included lactic acid, proline, methylmalonic acid, and glycerol.

Impact of the Findings

In their study paper, the researchers wrote that their findings suggest that novel attributes of gut microbiota play a role in plasma metabolite variation in women with gestational diabetes. They added that the study also suggests that the correlations observed between metabolites and hyperglycemia in this population could have been impacted by diet and changes in metabolic health.

References:

  • Dong L, Han L, Duan T, et al. Integrated microbiome–metabolome analysis reveals novel associations between fecal microbiota and hyperglycemia-related changes of plasma metabolome in gestational diabetes mellitus. RSC Adv. 2020;10:2027-2036.
  • Rodrigo N, Glastras SJ. The Emerging Role of Biomarkers in the Diagnosis of Gestational Diabetes Mellitus. J Clin Med. 2018;7(6).
  • Wang J, Zheng J, Shi W, et al. Dysbiosis of maternal and neonatal microbiota associated with gestational diabetes mellitus. Gut. 2018;67(9):1614-1625.
  • Martineau MG, Raker C, Dixon PH, et al. The metabolic profile of intrahepatic cholestasis of pregnancy is associated with impaired glucose tolerance, dyslipidemia, and increased fetal growth. Diabetes Care. 2015;38(2):243-8.
  • Dudzik D, Zorawski M, Skotnicki M, et al. GC-MS based Gestational Diabetes Mellitus longitudinal study: Identification of 2-and 3-hydroxybutyrate as potential prognostic biomarkers. J Pharm Biomed Anal. 2017;144:90-98.

Bruker Avance III HD 600 MHz NMR Spectrometer. City University of New York. https://asrc.gc.cuny.edu/structbio/facilities/nmr-spectroscopy/instrument-list/bruker-avance-iii-hd-600-mhz-nmr-spectrometer/