# Gut microbiota contributes to gestational diabetes mellitus by interfering with bile acid metabolism and resistin

## TL;DR

This study shows that gut bacteria from gestational diabetes patients can cause metabolic issues in mice by affecting bile acids and inflammation.

## Contribution

The study establishes a causal link between gut microbiota from GDM patients and metabolic dysfunction in mice through microbiota transplantation.

## Key findings

- Gut microbiota from GDM patients induced glucose intolerance in mice.
- Microbiota changes included increased Akkermansia and Faecalibaculum and decreased Lachnospiraceae_FCS020_group.
- Bile acid levels and resistin were altered, correlating with metabolic markers like HOMA-IR and GTT-AUC.

## Abstract

Gestational diabetes mellitus (GDM) affects 6% to 15% of pregnancies globally, as a severe metabolic disorder that impairs offspring health. Mounting evidence highlights the critical role of gut microbiota in metabolic regulation, yet the causal relationship between gut microbiota and GDM pathogenesis remains unclear. This study aimed to clarify this causal link and explore the underlying mechanisms.

An innovative human microbiota transplantation approach was adopted. Gut microbiota from GDM patients was transplanted into antibiotic-treated C57BL/6J mice. 16S rRNA sequencing was used to analyze the structural changes of gut microbiota in recipient mice, and metabolomics was employed to detect changes in circulating bile acid levels. For mechanism exploration, Luminex assay was used to detect multiple inflammatory factors, enzyme-linked immunosorbent assay (ELISA) was applied to measure lipopolysaccharide (LPS) levels, and Western blot (WB) was utilized to determine the expression of intestinal barrier protein.

Transplantation of gut microbiota from GDM patients directly induced glucose intolerance in pregnant antibiotic-treated C57BL/6J mice. 16S rRNA sequencing showed significant structural reorganization of the gut microbiota in GDM microbiota recipients, characterized by decreased abundance of Lachnospiraceae_FCS020_group and increased abundance of Akkermansia, Faecalibaculum, and Bilophila. These microbiota dysregulations led to reduced expression of the intestinal barrier protein Claudin-1, elevated serum lipopolysaccharide (LPS) levels, and increased resistin and matrix metalloproteinase 9 (MMP-9) levels. Metabolomic analysis revealed decreased circulating primary bile acids (cholic acid [CA] and chenodeoxycholic acid [CDCA]) and secondary bile acid deoxycholic acid (DCA). Correlation analysis indicated a positive correlation between Faecalibaculum and DCA, CDCA, as well as resistin. DCA and CDCA were significantly negatively correlated with HOMA-IR, while resistin was significantly positively correlated with GTT-AUC, FINS, and HOMA-β%.

These findings suggest that the imbalance in bile acid metabolism and mild inflammatory response caused by dysregulated gut microbiota is an adjustable environmental driving factor in the pathophysiological process of GDM.

In this study, fecal microbiota transplantation (FMT) was employed to transfer the gut microbiota from patients with gestational diabetes mellitus (GDM) into antibiotic-treated mice. Techniques including 16S rRNA sequencing, liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis, Luminex-based inflammatory factor detection, ELISA, and Western blot were also applied to investigate the associations among gut microbiota, metabolomics, and inflammatory factors in GDM model mice.Scientific illustration shows the workflow of a gestational diabetes mellitus (GDM) research study involving human feces transplantation into antibiotic-treated (ABX) mice, followed by fecal, colon, and serum analyses using 16SrRNA sequencing, western blot, metabolomics, and Luminex. Data visualizations include bar charts, a cladogram, a heatmap, and correlation matrices to represent microbial and metabolite differences.

In this study, fecal microbiota transplantation (FMT) was employed to transfer the gut microbiota from patients with gestational diabetes mellitus (GDM) into antibiotic-treated mice. Techniques including 16S rRNA sequencing, liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis, Luminex-based inflammatory factor detection, ELISA, and Western blot were also applied to investigate the associations among gut microbiota, metabolomics, and inflammatory factors in GDM model mice.