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肠道微生物组作为外分泌胰腺功能不全猪模型中胰腺酶替代治疗的反应标志物。

Gut microbiome as a response marker for pancreatic enzyme replacement therapy in a porcine model of exocrine pancreas insufficiency.

机构信息

Biomedical Technology Center of the Medical Faculty, University of Muenster, Mendelstrasse 17, 48149, Muenster, Germany.

Institute of Hygiene, University of Muenster, 48149, Muenster, Germany.

出版信息

Microb Cell Fact. 2020 Dec 3;19(1):221. doi: 10.1186/s12934-020-01482-2.

DOI:10.1186/s12934-020-01482-2
PMID:33272255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7713139/
Abstract

BACKGROUND

Exocrine pancreatic insufficiency (EPI) is characterized by the loss of active pancreatic enzymes and a resulting severely reduced food digestion. EPI therapy requires orally applied pancreatic enzyme replacement. The gut microbiome is a known mediator of intestinal diseases and may influence the outcome of EPI and the effects of a pancreatic enzyme replacement therapy (PERT). Here, we analyzed the effects of EPI and PERT on the gut microbiome in the model of pancreatic duct ligated minipigs.

RESULTS

The microbial community composition in pig feces was analyzed by next generation sequencing of 16S rRNA amplicons. The data were evaluated for α- and β-diversity changes and changes at the different Operational Taxonomic Unit (OTU) levels by Shannon-Wiener and inverse Simpson index calculation as well as by Principal Coordinates Analysis based on Bray-Curtis dissimilarity. Microbial α-diversity was reduced after EPI induction and reverted to nearly healthy state after PERT. Analysis of microbial composition and β-diversity showed distinctive clusters of the three study groups and a change towards a composition comparable to healthy animals upon PERT. The relative abundance of possible pathobionts like Escherichia/Shigella, Acinetobacter or Stenotrophomonas was reduced by PERT.

CONCLUSION

These data demonstrate that EPI-induced dysbiosis could be reverted by PERT to a nearly healthy state. Elevated α-diversity and the reduction of bacterial overgrowth after PERT promises benefits for EPI patients. Non-invasive microbiome studies may be useful for EPI therapy monitoring and as marker for response to PERT.

摘要

背景

外分泌胰腺功能不全(EPI)的特征是活性胰腺酶的丧失,导致食物消化严重减少。EPI 治疗需要口服应用胰腺酶替代物。肠道微生物组是已知的肠道疾病的介质,可能会影响 EPI 的结果和胰腺酶替代治疗(PERT)的效果。在这里,我们分析了 EPI 和 PERT 对结扎胰管小型猪模型中肠道微生物组的影响。

结果

通过对 16S rRNA 扩增子的下一代测序分析了猪粪便中的微生物群落组成。通过 Shannon-Wiener 和倒数 Simpson 指数计算以及基于 Bray-Curtis 不相似性的主坐标分析,评估了 α-和β-多样性变化以及不同操作分类单元(OTU)水平的变化。EPI 诱导后微生物 α-多样性降低,PERT 后恢复到接近健康状态。微生物组成和β-多样性分析显示,三组研究之间存在明显的聚类,并且在 PERT 后,其组成向类似于健康动物的方向转变。PERT 降低了可能的条件致病菌如大肠杆菌/志贺氏菌、不动杆菌或嗜麦芽窄食单胞菌的相对丰度。

结论

这些数据表明,PERT 可使 EPI 诱导的肠道菌群失调恢复到接近健康的状态。PERT 后 α-多样性增加和细菌过度生长减少,为 EPI 患者带来了益处。非侵入性微生物组研究可能有助于 EPI 治疗监测,并作为对 PERT 反应的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/cc63435449ce/12934_2020_1482_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/10784f1dfa44/12934_2020_1482_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/fb2047d6a454/12934_2020_1482_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/59e819ba856e/12934_2020_1482_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/2abe4402f7cd/12934_2020_1482_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/cc63435449ce/12934_2020_1482_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/10784f1dfa44/12934_2020_1482_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/fb2047d6a454/12934_2020_1482_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/59e819ba856e/12934_2020_1482_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/2abe4402f7cd/12934_2020_1482_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52bb/7713139/cc63435449ce/12934_2020_1482_Fig5_HTML.jpg

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