Interaction between orally administrated heparin and intestinal microbiota in mice.

Xue Zhou; Yi Wang; Dong HE; Wen Zeng; Chong Zhang; Zhenglian Xue; Xinhui Xing

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Interaction between orally administrated heparin and intestinal microbiota in mice.

Author: Xue ZHOU ¹ ; Yi WANG ^{2
,

3} ; Dong HE ^{2
,

3} ; Wen ZENG ^{2
,

3} ; Chong ZHANG ^{2
,

3} ; Zhenglian XUE ¹ ; Xinhui XING ^{2
,

3}
Author Information

1. College of Biological and Chemical Engineering, Anhui Polytechnic University, Wuhu 241000, Anhui, China.
2. Key Laboratory of Industrial Biocatalysis of Ministry of Education, Institute of Biochemical Engineering, Department of Chemical Engineering
3. Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China.
Publication Type:Journal Article
Keywords: degradation; gastrointestinal tract; gut microbiota; heparin; oral administration
MeSH: Animals; Gastrointestinal Microbiome; Heparin; Mice; Mice, Inbred C57BL; RNA, Ribosomal, 16S
From: Chinese Journal of Biotechnology 2019;35(9):1736-1749
CountryChina
Language:Chinese
Abstract: The development of orally administrated heparin drugs requires a systematic understanding of the interaction between heparin and gut flora. The in vivo distribution of fluorescein-labeled heparin that is orally administrated by mice was observed using fluorescein microscopy. In addition, the stability of heparin in simulated gastric and intestinal fluids, as well as the in vitro degradation of heparin by gut flora were detected by HPLC. The results show that orally administrated heparin was mainly distributed in the gastrointestinal tract of mice, and exerted structural stability under the condition of simulated gastric and intestinal fluids in vitro. However, heparin could be degraded by intestinal flora cultured in medium containing heparin. In order to further study the effect of orally administrated heparin on intestinal flora in mice, the fecal microbiota 16S rRNA fragment of C57BL/6J mice was tested by the Illumina Mi-Seq high-throughput sequencing technology. Compared with the gut flora of mice that orally administrated by saline, the biodiversity of gut flora in mice with orally administrated heparin was decreased. The difference of microflora structure was not significant at the phylum level, and the relative abundance of Alistipes, Parasutterella and Akkermansia was increased at the genus level, and the relative abundance of Bilophila, Enterorhabdus, Ruminiclostridium, Prevotellaceae_UCG_001, Ruminiclostridium-9, Bacteroides, Lachnoclostridium, Candidatus, Saccharimonas, Intestinimonas and Dubosiella was reduced. These findings indicate that heparin could influence the gut flora of mice. In addition, no obvious toxic and side effects were found in mice that orally administrated heparin, suggesting the safety of orally administrated heparin.