Glucagon-like peptide (GLP) -2 improved colonizing bacteria and reduced severity of ulcerative colitis by enhancing the diversity and abundance of intestinal mucosa

ABSTRACT

The global incidence of ulcerative colitis (UC) continues to increase while it’s clinical cure rate remains low. Intestinal mucosal ulcers have segmental distribution and variable severity. Intestinal bacteria are closely related to intestinal immunity and metabolism; however, the relationship between intestinal microbiome profile and the occurrence of UC, as well as the contribution of glucose metabolism, are not well understood. This was investigated in the present study using mucosal biopsies from patients with UC and healthy control subjects. We performed high throughput 16S rRNA gene sequencing to estimate microbiota composition and abundance as well as their association with clinical indices such as lesion severity. The results showed that the diversity and abundance of intestinal microbiota were significantly lower in patients with UC than in healthy subjects; however, these were unrelated to ulcer severity. Serum glucagon-like peptide 2 (GLP-2) level was associated with reduced microbiota diversity and abundance in UC. These results indicate that colonization by specific microbiota is not the main determinant of pathologic status in UC. Additionally, therapeutic strategies that increase GLP-2 levels in intestinal mucosa may be effective in the treatment of UC.

Graphical abstract

KEYWORDS:

• Glucagon-like peptide 2
• high-throughput 16S RNA sequencing
• glucose metabolism analysis
• intestinal microbiota
• ulcerative colitis

Data accessibility

Raw sequences generated by 16S rRNA sequencing have been deposited in the NCBI Sequence Read Archive (SRA: SUB8157907; Study PRJNA664267), and the relevant metadata can be found at https://www.ncbi.nlm.nih.gov/Traces/study/ under the SRA accession number.

Ethics approval and consent to participate

This study was approved by the Research Ethics Committee of the First Affiliated Hospital of Harbin Medical University (approval no. IRB-AF/SC-04/01.0). Experiments were performed in strict accordance with international guidelines regarding the conduct of clinical trials, and each patient provided written, informed consent.

Disclosure statement

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

Author contributions

Dongyue Li and Hongyu Kuang made substantial contributions to study conception and design and data acquisition. Youlin Yang performed quality control of clinical samples. Dongyue Li, Xunhai Yin, Ping Huang, Wenbo Ding, and Huichao Zhang collected samples. Hongyu Xu and Yu Ni performed clinical diagnosis and treatment. Dongyue Li and Sijia Niu performed bioinformatics and statistical analyses and interpreted the data. Dongyue Li wrote the manuscript. All authors read and approved the final manuscript.