Kazak faecal microbiota transplantation induces short-chain fatty acids that promote glucagon-like peptide-1 secretion by regulating gut microbiota in db/db mice

Abstract

Context

Faecal microbiota transplantation (FMT) from Kazak individuals with normal glucose tolerance (KNGT) significantly reduces plasma glycolipid levels in type 2 diabetes mellitus db/db mice. However, the mechanism behind this effect has not been reported.

Objective

To study the mechanism of improved glycolipid disorders in db/db mice by FMT from a KNGT donor.

Materials and methods

The normal diet group consisted of db/m mice orally administered 0.2 mL phosphate buffer saline (PBS) (db/m + PBS). For the db/db + PBS (Vehicle) and db/db + KNGT (FMT intervention group) groups, db/db mice received oral 0.2 mL PBS or faecal microorganisms from a KNGT donor, respectively. All mice were treated daily for 0, 6 or 10 weeks. Faecal DNA samples were sequenced and quantified using 16S rRNA gene sequencing and RT-qPCR, respectively. Short-chain fatty acid (SCFA) levels in the mouse faeces were determined by gas chromatography. G protein-coupled receptor 43 (GPR43) and glucagon-like peptide-1 (GLP-1) expression levels were determined.

Results

FMT intervention significantly increased the relative abundance of Bacteroides uniformis (0.038%, p < 0.05). Clostridium levels (LogSQ) were increased (p < 0.01), while Mucispirillum schaedleri levels (LogSQ) were decreased (p < 0.01). Acetate and butyrate levels in the faeces were significantly increased (acetate; butyrate: 22.68 ± 1.82 mmol/L; 4.13 ± 1.09 mmol/L, p < 0.05). GPR43 mRNA expression and GLP-1 protein expression increased in colon tissue (p < 0.05).

Discussion and conclusions

Mechanistically, FMT-KNGT could improve glycolipid disorders by changing the bacterial composition responsible for producing SCFAs and activating the GPR43/GLP-1 pathway.

Keywords:

• Kazak individuals
• type 2 diabetes mellitus
• short-chain fatty acids-producing bacteria

Acknowledgements

The work was completed in Central Laboratory of Xinjiang Medical University. We are also grateful to Kazaks donors for their help in this research and to the Laboratory Animal Centre of Xinjiang Medical University.

Disclosure statement

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

Additional information

Funding

This work was supported by the National Natural Science Foundation of China–Xinjiang Joint Fund under Grant [U1403322]; National Natural Science Foundation of China under Grant [No. 81360504].