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. 2023 Jan-Dec;15(1):2154552.
doi: 10.1080/19490976.2022.2154552.

Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans

Dewei Ye  1   2   3   4 , Jiating Huang  1   2   3   5 , Jiaming Wu  1   2   3   4 , Kang Xie  1   2 , Xiang Gao  1   2 , Kaixuan Yan  1   2   3   4 , Pengfei Zhang  1   2   3   4 , Ying Tao  6 , Yun Li  6 , Shufei Zang  7 , Xianglu Rong  1   2   3 , Jun Li  5   8   9 , Jiao Guo  1   2   3
Affiliations

Integrative metagenomic and metabolomic analyses reveal gut microbiota-derived multiple hits connected to development of gestational diabetes mellitus in humans

Dewei Ye et al. Gut Microbes. 2023 Jan-Dec.

Abstract

Gestational diabetes mellitus (GDM) is characterized by the development of hyperglycemia and insulin resistance during the second or third trimester of pregnancy, associated with considerable risks to both the mother and developing fetus. Although emerging evidence suggests an association between the altered gut microbiota and GDM, remarkably little is known about the microbial and metabolic mechanisms that link the dysbiosis of the gut microbiota to the development of GDM. In this study, a metagenome-wide association study and serum metabolomics profiling were performed in a cohort of pregnant women with GDM and pregnant women with normal glucose tolerance (NGT). We identified gut microbial alterations associated with GDM and linked to the changes in circulating metabolites. Blood metabolite profiles revealed that GDM patients exhibited a marked increase in 2-hydroxybutyric acid and L-alpha-aminobutyric acid, but a decrease in methionine sulfoxide, allantoin, and dopamine and dopaminergic synapse, when compared with those in NGT controls. Short-chain fatty acid-producing genera, including Faecalibacterium, Prevotella, and Streptococcus, and species Bacteroides coprophilus, Eubacterium siraeum, Faecalibacterium prausnitzii, Prevotella copri, and Prevotella stercorea, were significantly reduced in GDM patients relative to those in NGT controls. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented as the core species in GDM patients. These microbial and metabolic signatures are closely associated with clinical parameters of glucose metabolism in GDM patients and NGT controls. In conclusion, we identified circulating dopamine insufficiency, imbalanced production of SCFAs, and excessive metabolic inflammation as gut microbiota-driven multiple parallel hits linked to GDM development. This work might explain in part the mechanistic link between altered gut microbiota and GDM pathogenesis, and suggest that gut microbiota may serve as a promising target to intervene in GDM.

Keywords: Glucose intolerance; insulin resistance; metabolic inflammation; microbial metabolite.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Alterations in gut microbiome and blood metabolites in GDM patients and pregnant women with NGT.
Figure 2.
Figure 2.
Analysis of gut bacterial co-occurrence network in GDM patients and pregnant women with NGT.
Figure 3.
Figure 3.
Analysis of core species in gut bacterial co-occurrence network in GDM patients and pregnant women with NGT.
Figure 4.
Figure 4.
Association of gut microbial species with blood glucose level during oral glucose tolerance testing in GDM patients and pregnant women with NGT.
Figure 5.
Figure 5.
Association of representative gut microbial species and circulating metabolites with clinical indices.
Figure 6.
Figure 6.
Association of gut microbial species with circulating metabolites.
Figure 7.
Figure 7.
Schematic representation of mechanistic insights provided by the integrative metagenomic and metabolomic analyses in the present study of GDM development.
See this image and copyright information in PMC

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