Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury

Bo Cao; Rui-Yang Zhao; Hang-Hang Li; Xing-Ming Xu; Hao Cui; Huan Deng; Lin Chen; Bo Wei

doi:10.1186/s40779-022-00397-w

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Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury

RESEARCH | Updated：2023-03-23

- Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury
- Military Medical Research Vol. 10, Issue 1, Pages: 78-93(2023)
- Affiliations：
  
  1.Department of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853 , China
  2.Medical School of Chinese PLA, Beijing 100853, China
- Author bio：
  
  * weibo@vip.163.com
- Funds：
- DOI：10.1186/s40779-022-00397-w
  CLC：
- Published：2023-02
- Accepted：
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Cao B, Zhao RY, Li HH, Xu XM, Cui H, Deng H, et al. Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury. Mil Med Res. 2022;9(1):37.
DOI：

Cao B, Zhao RY, Li HH, Xu XM, Cui H, Deng H, et al. Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury. Mil Med Res. 2022;9(1):37. DOI： 10.1186/s40779-022-00397-w.

摘要

Abstract

Background:

Traumatic colon injury (TCI) is a common disease during wartime. Prolongation of posttraumatic survival time is an effective approach to patient outcome improvement. However

there is a lack of basic research in this field. This study aimed to elucidate the mechanisms underlying TCI progression and to develop novel regimens to buy time for TCI patients on the battlefield.

Methods:

A total of 669 Sprague–Dawley rats were used in this study. Surgical colon incision was performed to generate the TCI rat model. The landscape of colon microbiota compositions was depicted using 16S rRNA sequencing and metabolites in the intestinal contents were detected by metabolomics profiling. The signaling transduction in the intestinal epithelium was investigated using antibody microarrays and Western blotting. The enzyme-linked immunosorbent assay (ELISA) was conducted to measure the levels of interleukin-6 and tumor necrosis factor-α in intestines and plasma for the detection of inflammatory responses. Diamine oxidase

D-lactate and endotoxin in plasma and protein expression of zonula occludens 1 and occludin were selected as the indicators of intestinal barrier permeability. To investigate alterations of microbiota symbiosis

the relative abundances of specific bacterial genera were detected using quantitative real-time PCR (qRT-PCR).

Results:

As a type of lethal injury

TCI induced acute disruption of intestinal homeostasis

characterized by inflammatory responses

intestinal barrier hyperpermeability and microbiota dysbiosis (

0.05). Significant alterations in bacterial metabolic patterns were detected with decreases in many metabolites. After a series of screenings

we found that oral administration of asparagine (Asn) and 3-indolepropionic acid (IPA) effectively prolonged posttraumatic survival time [Asn plus IPA

. Vehicle: hazard ratio (

)=0.105

95%CI 0.031–0.356

=0.0003] and restored intestinal homeostasis in TCI rats (

0.05). Mechanistically

this combinational strategy protected the rats against TCI through synergistic activation of Akt signaling in the intestinal epithelium (

0.05).

Conclusions:

Abrupt dysregulation of intestinal homeostasis plays a critical role in the progression toward TCI induced death. Oral administration of Asn plus IPA may serve as an effective regimen to restore intestinal functions and prolong the posttraumatic survival time.

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references

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