Gestational diabetes mellitus is growing in prevalence worldwide. It is characterized by the body’s temporary inability to use insulin effectively because of insulin-blocking placenta hormones.
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Research has found that the prevalence of gestational diabetes has nearly doubled from 2006 to 2016, it heightens the health burden and costs associated with pregnancy. The reasons for this increase are unknown.
Even though studies have supplied researchers with more knowledge about the risk factors for the disease, a thorough understanding of the pathogenesis of gestational diabetes is lacking.
Researchers from China found novel associations between microbiota and glucose-related changes of plasma metabolome in patients with gestational diabetes, during an integrated microbiome-metabolome analysis. If replicated, findings from this study provide greater insight into the relationship between risk of gestational diabetes and gut microbiota changes.
Gut microbiota and gestational diabetes: Is there a link?
Research has linked alterations in gut microbiota in pregnant women with hyperglycemia. It is suggested that the gut microbiota may be a source of biomarkers for gestational diabetes based on these findings.
Generally, via the production of hormones necessary for fetal development and transfer of nutrients between the mother and fetus, pregnancy exerts metabolic stress on the body. These placenta hormones – including cortisol, estrogen, and lactogen – can “block” insulin, which is needed for normal glucose metabolism and regulation.
Metabolomics studies have demonstrated associations between triglycerides, 3-hydroxyisovalerate, b-hydroxybutyrate, and 2-hydroxyisobutyrate with a higher incidence of gestational diabetes.
While these and other metabolites have been involved in the risk of gestational diabetes, little data exists to describe the mediation influence of gut microbiota alterations on circulating metabolites in this disease.
1H-NMR spectrometry study examines microbiota of women with gestational diabetes
Researchers enrolled a total of 40 pregnant women who entered a hospital in China in a microbiota-metabolome association study. Half of the women had gestational diabetes, the others were included as non-diabetic controls.
In order to conduct a multi-omics association study, the researchers collected overnight fasting feces samples. The study was conducted with a 16s rRNA sequencing based fecal microbiota analysis and proton nuclear magnetic resonance (1H-NMR) profiling of the plasma metabolome.
The Bruker 600 MHz AVANCE III nuclear magnetic resonance (NMR) spectrometer was employed to carry out 1-H-NMR analysis. This platform features an Oxford Actively Shielded 14.1 Tesla standard bore magnet, 5 mm room temperature probehead (TXI 1H-31P/13C-2H + Z), 5 mm triple resonance inverse triple resonance inverse CryoProbe (TCI 1H&19F-13C/15N-2H + Z), and TopSpin 3.5 software.
1H-NMR spectrometry was conducted using pulse sequence Carr–Purcell–Meiboom–Gill (CPMG), scanning times 64 scans, spectral width 1235.7 Hz, spectral size 65,536 points, pulse width 40.5 ms, and relaxation delay 1.0 s.
Significant changes seen in microbiota
Fecal microbiota of patients with gestational diabetes was differentiated from the non-diabetes control group using statistical analysis, suggesting compositional changes along the vector of hyperglycemia.
Relative to the control group, fecal microbiota from those with gestational diabetes exhibited significant changes in alpha diversity (p=0.039) and beta diversity (p=3.41 x 10-6).
A total of 98 members of fecal microbiota also contributed to the correlation between alterations in fecal microbiota and hyperglycemia. Blautia was decreased in women with gestational diabetes, whereas Phascolarctobacterium, Alistipes, Parabacteroides, Eubacterium coprostanoligenes_group, Oscillibacter, Paraprevotella, and Ruminococcaceae NK4A214_group were heightened in these patients.
Overall, a population of Firmicutes of the fecal microbiota contributed to alterations in the plasma metabolome which were associated with gestational diabetes. This population included 15 genera, which were correlated positively with each other.
This finding, according to the researchers, signified synergistic gut bacteria influence on the changes in patients’ plasma metabolome. The researchers identified 5 plasma metabolites in a redundancy analysis, which contributed to the alterations in fecal microbiota of women with gestational diabetes.
These included lactic acid, glycerol, galactitol, proline, and methylmalonic acid. Compared to healthy controls, women with gestational diabetes had lower levels of methylmalonic acid.
According to the researchers, gut microbiota contributes to a high amount of the substrate of circulating methylmalonic acid. In a spearman rank correlation analysis, four out of the five plasma metabolites correlated with hyperglycemia. These metabolites included lactic proline, acid, methylmalonic acid and glycerol.
The researchers stated that the findings from this study show that novel attributes of the gut microbiota contribute to variability in plasma metabolites in women with gestational diabetes.
In addition to the associations between gut microbiota and plasma metabolites in gestational diabetes, the study also shows that the observed correlations could be affected by diet or changes in a pregnant woman’s metabolic health.
Validation studies are required in order to assess the contribution of the gut microbiota in gestational diabetes to plasma metabolome. These studies should be adjusted for patients’ metabolic statuses and dietary considerations.
- 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/. Accessed April 13, 2020.
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