Severe Intestinal Dysbiosis in Rat Models of Short Bowel Syndrome with Ileocecal Resection

Huang, Yuhua; Chen, Aoxue; Guo, Fan; Wang, Jian; Li, Yousheng

doi:10.1007/s10620-019-05802-4

Cited by 14 publications

(20 citation statements)

References 46 publications

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“…In order to dissect the intestine-specific effects of Teduglutide, small bowel tissue was examined. ICR alone resulted in significantly increased villus length and crypt depth by ~ 50%, as seen in vehicle-treated animals and consistent with previous studies [48,49]. In wt animals, Teduglutide significantly increased villus length further by ~ 15%.…”

Section: Discussionsupporting

confidence: 90%

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

et al. 2020

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Background In short bowel syndrome, epithelial surface loss results in impaired nutrient absorption and may lead to intestinal insufficiency or intestinal failure. Nucleotide oligomerization domain 2 (Nod2) dysfunction predisposes to the development of intestinal failure after intestinal resection and is associated with intestinal barrier defects. Epithelial barrier function is crucial for intestinal absorption and for intestinal adaptation in the short bowel situation. Aims The aim of the study was to characterize the effects of the GLP-2 analogue Teduglutide in the small intestine in the presence and absence of Nod2 in a mouse model of short bowel syndrome. Methods Mice underwent 40% ICR and were thereafter treated with Teduglutide versus vehicle injections. Survival, body weight, stool water, and sodium content and plasma aldosterone concentrations were determined. Intestinal and kidney tissue was examined with light and fluorescence microscopy, Ussing chamber studies and quantitative PCR in wild type and transgenic mice. Results Teduglutide reduced intestinal failure incidence in Nod2 k.o. mice. In wt mice, Teduglutide attenuated intestinal insufficiency as indicated by reduced body weight loss and lower plasma aldosterone concentrations, lower stool water content, and lower stool sodium losses. Teduglutide treatment was associated with enhanced epithelial paracellular pore function and enhanced claudin-10 expression in tight junctions in the villus tips, where it colocalized with sodium-glucose cotransporter 1 (SGLT-1), which mediates Na-coupled glucose transport. Conclusions In the SBS situation, Teduglutide not only maximizes small intestinal mucosal hypertrophy but also partially restores small intestinal epithelial function through an altered distribution of claudin-10, facilitating sodium recirculation for Na-coupled glucose transport and water absorption. Keywords Short bowel syndrome • Mouse model • Ussing chamber • Teduglutide • Barrier function • Nucleotide oligomerization domain 2 Abbreviations GLP-2 Glucagon-like peptide 2 Nod2 Nucleotide oligomerization domain 2 RAAS Renin-angiotensin-aldosterone system PS Parenteral support

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Section: Discussionsupporting

confidence: 90%

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

et al. 2020

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“…Detailed analysis of the composition and structure of intestinal bacteria in SBS demonstrated that, in comparison with Sham group, the relative abundance of 9 out of 11 phyla changed significantly, suggesting a thorough dysbiosis of intestinal bacteria in SBS rats. In line with previous studies, there existed a dramatic overabundance of Proteobacteria and its family Enterobacteriaceae in colonic contents of SBS rats, which contains a great number of pathogenic bacteria [ 2 , 25 , 26 ].…”

Section: Discussionsupporting

confidence: 83%

“…In the present study, we comprehensively described the intestinal bacterial and fungal dysbiosis in type 2 SBS rats with ileocecal resection, and found that GLP-2 treatment could partially attenuate the disturbance of intestinal microbiota. Although our previous studies have disclosed severe intestinal bacterial dysbiosis in animal models and patients with ileocecal resection [ 2 , 7 ], there is still no comprehensive assessment of intestinal fungal dysbiosis accompanied by intestinal bacterial dysbiosis in SBS. Due to the interkingdom interaction between bacteria and fungi, intestinal bacterial dysbiosis is likely to cause intestinal fungal dysbiosis, which may further aggravate the intestinal bacterial dysbiosis, and even exacerbate the intestinal inflammation and thus worsen the prognosis of the disease [ 19 – 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Short bowel syndrome (SBS), a main cause of intestinal failure, refers to a kind of disease presented as severe malnutrition, diarrhea, water and electrolyte disorder mainly resulting from massive small bowel resection [ 1 , 2 ]. The treatment of SBS is facing multiple challenges.…”

Section: Introductionmentioning

confidence: 99%

“…Unfortunately, intestinal flora dysbiosis in SBS can lead to intestinal mucosal inflammation, delayed enteral nutrition and prolonged use of parenteral nutrition, impaired intestinal adaptation, and finally resulting in poor prognosis [ 4 – 6 ]. Our Previous studies have also 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 ].…”

Section: Introductionmentioning

confidence: 99%

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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

Cheng

Fan

et al. 2021

BMC Infect Dis

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Background Previous 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. Methods 8-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. Results The 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. Conclusion Our study confirms the bacterial and fungal dysbiosis in type 2 SBS rats, and GLP-2 partially ameliorated these microbiota dysbiosis.

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Milk Fat Globule Membrane Enhances Colonic–Mucus‐Barrier Function in a Rat Model of Short‐Bowel Syndrome

Niu

et al. 2020

J Parenter Enteral Nutr

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Background Clinical research reveals that colon plays an important role in mitigating the effects of short‐bowel syndrome (SBS). Previously, we showed that the milk fat globule membrane (MFGM) had protective effects on gut barrier integrity in the rat SBS model. Here, we used the same rat model to investigate the effects of enteral MFGM supplementation on gut microbiota and colonic–mucus‐barrier function and its related mechanisms. Methods We randomly divided 24 male Sprague‐Dawley rats into 3 groups: Sham, SBS (rats with massive small‐bowel resection), and SBS+MFGM (SBS rats supplemented with 1.5 g/kg/d MFGM). We then evaluated gut permeability, crypt depth, goblet‐cell count, mucin 1 (MUC1), mucin 2 (MUC2), microbiota, short‐chain fatty acids, and protein expressions of nucleotide‐binding oligomerization domain, leucine‐rich repeat, and pyrin domain‐containing protein 6 (NLRP6) pathway of the colon. Results Compared with SBS rats, SBS+MFGM rats exhibited lower intestinal permeability, increased crypt depth, more goblet cells, and more MUC1/MUC2‐positive cells. The SBS+MFGM group also had greater Firmicutes abundance and lower acetate concentration (P < .05). Sham rats had significantly lower Bacteroidetes abundance than SBS rats, but SBS+MFGM and SBS groups did not differ. Additionally, the SBS+MFGM group had higher NLRP6 and interleukin (IL)‐18 expression but lower IL‐1β and Caspase‐1 (cysteinyl aspartate‐specific protease‐1) expression than the SBS group (P < .05). Conclusion Supplementation of MFGM modulates gut microbiota composition in SBS, possibly through strengthening the colonic mucus barrier and regulation of NLRP6 inflammasome.

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Severe Intestinal Dysbiosis in Rat Models of Short Bowel Syndrome with Ileocecal Resection

Cited by 14 publications

References 46 publications

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

Teduglutide Promotes Epithelial Tight Junction Pore Function in Murine Short Bowel Syndrome to Alleviate Intestinal Insufficiency

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

Milk Fat Globule Membrane Enhances Colonic–Mucus‐Barrier Function in a Rat Model of Short‐Bowel Syndrome

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