# Fecal microbiota transplantation from gestational diabetes mellitus patients induces glucose intolerance and subclinical inflammation in mice

## TL;DR

Transplanting gut microbes from women with gestational diabetes into mice causes diabetes-like symptoms and inflammation, offering a new way to study the condition.

## Contribution

A novel fecal microbiota transplantation model that accurately replicates gestational diabetes features in mice.

## Key findings

- GDM-FMT mice showed glucose intolerance, insulin resistance, and increased inflammation.
- Gut microbiota diversity was reduced, with higher Firmicutes/Bacteroidota ratios in GDM-FMT mice.
- The FMT model outperformed traditional methods in replicating GDM metabolic and microbial features.

## Abstract

The pathogenesis of gestational diabetes mellitus (GDM) is not fully understood, with gut microbiota dysbiosis emerging as a potential contributing factor. Existing animal models primarily mimic type 1 or type 2 diabetes, inadequately representing GDM. This study aimed to investigate whether fecal microbiota transplantation (FMT) from GDM patients is associated with the development of GDM-like phenotypes in mice, comparing this approach to traditional modeling methods.

Fecal microbiota from GDM patients and healthy controls were transplanted into antibiotic-treated pregnant mice, creating trimester-specific FMT models. Control groups included mice on a high-fat diet (HFD) and HFD combined with streptozotocin (STZ). Metabolic phenotypes were assessed via glucose and insulin tolerance tests, fasting blood glucose, and insulin measurements. Serum inflammatory markers were analyzed, and gut inflammation was evaluated. 16S rRNA sequencing was performed on key model groups.

Mice receiving FMT from mid-late trimester GDM donors or traditional treatments developed significant glucose intolerance, insulin resistance, and gestational weight gain. Serum levels of inflammatory factors (e.g., IL-1β, MMP-9) were elevated. 16S rRNA sequencing revealed markedly reduced gut microbiota diversity and increased Firmicutes/Bacteroidota ratio in both GDM-FMT and traditional model groups, with similar microbial community structures and alterations in metabolic and inflammation-related pathways.

Gut microbiota from GDM patients may disrupt glucose homeostasis and contribute to a pro-inflammatory state during pregnancy. The GDM-FMT model effectively recapitulates key metabolic, inflammatory, and microbial dysbiosis features of GDM, providing a novel and reliable experimental tool for mechanistic studies.

Compared with traditional methods, the FMT-induced model successfully recapitulated key features of GDM—glucose intolerance, subclinical inflammation, and gut dysbiosis—and thus serves as a viable method for GDM phenotype simulation.Diagram illustrating the experimental design for studying gestational diabetes mellitus (GDM) using mouse models. The top section shows two comparisons: Model-1 uses a high-fat diet versus maintenance chow, while Model-2 uses a high-fat diet plus streptozotocin versus maintenance chow plus sodium citrate buffer. The second section compares models 3 to 5, featuring fecal microbiota transplantation from GDM patients to ABX mice versus control. The process involves monitoring weight, glucose tolerance tests, Luminex assays, histological analysis, and 16S rRNA sequencing. Bullet points summarize findings related to gut dysbiosis, inflammatory factors, and pathogen transmission.

Compared with traditional methods, the FMT-induced model successfully recapitulated key features of GDM—glucose intolerance, subclinical inflammation, and gut dysbiosis—and thus serves as a viable method for GDM phenotype simulation.