Therapeutic potential of an intestinotrophic hormone, glucagon-like peptide 2, for treatment of type 2 short bowel syndrome rats with intestinal bacterial and fungal dysbiosis

Xiuting Hu,Xi Chen,Yuhua Huang,Jian Wang,Zhiwei Jiang,Shengxian Fan,Wei Cheng

doi:10.1186/s12879-021-06270-w

Abstract

BackgroundPrevious studies showed that type 2 short bowel syndrome (SBS) rats were accompanied by severe intestinal bacterial dysbiosis. Limited data are available for intestinal fungal dysbiosis. Moreover, no effective therapeutic drugs are available for these microbiota dysbiosis. The aims of our study were to investigate the therapeutic potential of glucagon-like peptide 2 (GLP-2) for these microbiota dysbiosis in type 2 SBS rats.Methods8-week-old male SD rats which underwent 80% small bowel resection, ileocecum resection, partial colon resection and jejunocolostomy, were treated with saline (SBS group, n = 5) or GLP-2 (GLP2.SBS group, n = 5). The Sham group rats which underwent transection and re-anastomosis were given a saline placebo (Sham group, n = 5). 16S rRNA and ITS sequencing were applied to evaluate the colonic bacterial and fungal composition at 22 days after surgery, respectively.ResultsThe relative abundance of Actinobacteria, Firmicutes and proinflammatory Proteobacteria increased significantly in SBS group rats, while the relative abundance of Bacteroidetes, Verrucomicrobia and Tenericutes decreased remarkably. GLP-2 treatment significantly decreased Proteus and increased Clostridium relative to the saline treated SBS rats. The diversity of intestinal fungi was significantly increased in SBS rats, accompanied with some fungi abnormally increased and some resident fungi (e.g., Penicillium) significantly decreased. GLP-2 treatment significantly decreased Debaryomyces and Meyerozyma, and increased Penicillium. Moreover, GLP-2 partially restored the bacteria-fungi interkingdom interaction network of SBS rats.ConclusionOur study confirms the bacterial and fungal dysbiosis in type 2 SBS rats, and GLP-2 partially ameliorated these microbiota dysbiosis.

Highlights

Previous studies showed that type 2 short bowel syndrome (SBS) rats were accompanied by severe intestinal bacterial dysbiosis
glucagon-like peptide 2 (GLP-2) partially reversed intestinal bacterial dysbiosis in SBS rats Rarefaction analysis demonstrated that the estimated operational taxonomical units (OTUs) richness could approach saturation in each sample (Fig. 1C)
The OTU counts index in SBS and GLP2.SBS group were dramatically lower than that of Sham group, indicating SBS induced a significant decrease in intestinal flora diversity (Fig. 1C-D)

Summary

Introduction

Previous studies showed that type 2 short bowel syndrome (SBS) rats were accompanied by severe intestinal bacterial dysbiosis. The aims of our study were to investigate the therapeutic potential of glucagon-like peptide 2 (GLP-2) for these microbiota dysbiosis in type 2 SBS rats. Gut microbiota dysbiosis is another great challenge for SBS patients [3, 4]. Intestinal flora dysbiosis in SBS can lead to intestinal mucosal inflammation, delayed enteral nutrition and prolonged use of parenteral nutrition, impaired intestinal adaptation, and resulting in poor prognosis [4,5,6]. Our Previous studies have disclosed that the composition of intestinal flora was altered in type 2 SBS patients and rats, which have an enterocolonic anastomosis and without ileocecal region [2, 7]

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