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
- Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury
- 解放军医学杂志（英文版） 2023年10卷第1期页码：78-93
- 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：
  
  the National Basic Research Program of China(2019YFB1311505);the National Natural Science Foundation of China(82073192;81773135)
- DOI：10.1186/s40779-022-00397-w
  中图分类号：
- 纸质出版：2023-02
- Accepted：
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Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury[J]. 解放军医学杂志（英文版）, 2023,10(1):78-93.

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.
Oral administration of asparagine and 3-indolepropionic acid prolongs survival time of rats with traumatic colon injury[J]. 解放军医学杂志（英文版）, 2023,10(1):78-93. DOI： 10.1186/s40779-022-00397-w.

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

Owens BD , Kragh JF Jr , Wenke JC , Macaitis J , Wade CE , Holcomb JB . Combat wounds in operation Iraqi Freedom and operation Enduring Freedom . J Trauma . 2008 ; 64 ( 2 ): 295 - 9 .

Belmont PJ Jr , McCriskin BJ , Sieg RN , Burks R , Schoenfeld AJ . Combat wounds in Iraq and Afghanistan from 2005 to 2009 . J Trauma Acute Care Surg . 2012 ; 73 ( 1 ): 3 - 12 .

Arafat S , Alsabek MB , Ahmad M , Hamo I , Munder E . Penetrating abdominal injuries during the Syrian war: patterns and factors affecting mortality rates . Injury . 2017 ; 48 ( 5 ): 1054 - 7 .

Feliciano DV , Rozycki GS . The management of penetrating abdominal trauma . Adv Surg . 1995 ; 28 : 1 - 39 .

Brady RR , O’Neill S , Berry O , Kerssens JJ , Yalamarthi S , Parks RW . Traumatic injury to the colon and rectum in Scotland: demographics and outcome . Colorectal Dis . 2012 ; 14 ( 1 ): e16 - 22 .

Tatebe LC , Jennings A , Tatebe K , Handy A , Prajapati P , Smith M , et al . Traumatic colon injury in damage control laparotomy-A multicenter trial: is it safe to do a delayed anastomosis? J Trauma Acute Care Surg . 2017 ; 82 ( 4 ): 742 - 9 .

Fouda E , Emile S , Elfeki H , Youssef M , Ghanem A , Fikry AA , et al . Indications for and outcome of primary repair compared with faecal diversion in the management of traumatic colon injury . Colorectal Dis . 2016 ; 18 ( 8 ): O283 - 91 .

Smith IM , Naumann DN , Marsden MER , Ballard M , Bowley DM . Scanning and war: utility of FAST and CT in the assessment of battlefield abdominal trauma . Ann Surg . 2015 ; 262 ( 2 ): 389 - 96 .

Metidji A , Omenetti S , Crotta S , Li Y , Nye E , Ross E , et al . The environmental sensor AHR protects from inflammatory damage by maintaining intestinal stem cell homeostasis and barrier integrity . Immunity . 2018 ; 49 ( 2 ): 353-62.e5 .

Wu Z , Huang S , Li T , Li N , Han D , Zhang B , et al . Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis . Microbiome . 2021 ; 9 ( 1 ): 184 .

Brown EM , Sadarangani M , Finlay BB . The role of the immune system in governing host-microbe interactions in the intestine . Nat Immunol . 2013 ; 14 ( 7 ): 660 - 7 .

Grosheva I , Zheng D , Levy M , Polansky O , Lichtenstein A , Golani O , et al . High-throughput screen identifies host and microbiota regulators of intestinal barrier function . Gastroenterology . 2020 ; 159 ( 5 ): 1807 - 23 .

van Konijnenburg DPH , Reis BS , Pedicord VA , Farache J , Victora GD , Mucida D . Intestinal epithelial and intraepithelial T cell crosstalk mediates a dynamic response to infection . Cell . 2017 ; 171 ( 4 ): 783-94.e13 .

Panpetch W , Hiengrach P , Nilgate S , Tumwasorn S , Somboonna N , Wilantho A , et al . Additional Candida albicans administration enhances the severity of dextran sulfate solution induced colitis mouse model through leaky gut-enhanced systemic inflammation and gut-dysbiosis but attenuated by Lactobacillus rhamnosus L34 . Gut Microbes . 2020 ; 11 ( 3 ): 465 - 80 .

McCormack SA , Tague LL , Gragoe EJ Jr , Johnson LR . Regulation of ornithine decarboxylase activity in LoVo cells . Am J Physiol . 1990 ; 258 ( 6 Pt 1 ): G934 - 41 .

Wang X , Liu Y , Li S , Pi D , Zhu H , Hou Y , et al . Asparagine attenuates intestinal injury, improves energy status and inhibits AMP-activated protein kinase signalling pathways in weaned piglets challenged with Escherichia coli lipopolysaccharide . Br J Nutr . 2015 ; 114 ( 4 ): 553 - 65 .

Chen S , Liu Y , Wang X , Wang H , Li S , Shi H , et al . Asparagine improves intestinal integrity, inhibits TLR4 and NOD signaling, and differently regulates p38 and ERK1/2 signaling in weanling piglets after LPS challenge . Innate Immun . 2016 ; 22 ( 8 ): 577 - 87 .

Zhu H , Pi D , Leng W , Wang X , Hu CA , Hou Y , et al . Asparagine preserves intestinal barrier function from LPS-induced injury and regulates CRF/CRFR signaling pathway . Innate Immun . 2017 ; 23 ( 6 ): 546 - 56 .

Zhao ZH , Xin FZ , Xue Y , Hu Z , Han Y , Ma F , et al . Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats . Exp Mol Med . 2019 ; 51 ( 9 ): 1 - 14 .

Xiao HW , Cui M , Li Y , Dong JL , Zhang SQ , Zhu CC , et al . Gut microbiotaderived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein . Microbiome . 2020 ; 8 ( 1 ): 69 .

Knott SRV , Wagenblast E , Khan S , Kim SY , Soto M , Wagner M , et al . Asparagine bioavailability governs metastasis in a model of breast cancer . Nature . 2018 ; 554 ( 7692 ): 378 - 81 .

Sogabe N , Mizoi L , Asahi K , Ezawa I , Goseki-Sone M . Enhancement by lactose of intestinal alkaline phosphatase expression in rats . Bone . 2004 ; 35 ( 1 ): 249 - 55 .

Pugine SMP , et al . Effect of indole-3-acetic acid administration by gavage and by subcutaneous injection on rat leukocytes . Cell Biochem Funct . 2007 ; 25 ( 6 ): 723 - 30 .

Hwang IK , Yoo KY , Li H , Park OK , Lee CH , Choi JH , et al . Indole-3-propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus . J Neurosci Res . 2009 ; 87 ( 9 ): 2126 - 37 .

Hirai H , Sootome H , Nakatsuru Y , Miyama K , Taguchi S , Tsujioka K , et al . MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo . Mol Cancer Ther . 2010 ; 9 ( 7 ): 1956 - 67 .

Lemke LE , Paine-Murrieta GD , Taylor CW , Powis G . Wortmannin inhibits the growth of mammary tumors despite the existence of a novel wortmannin-insensitive phosphatidylinositol-3-kinase . Cancer Chemother Pharmacol . 1999 ; 44 ( 6 ): 491 - 7 .

Gao M , Yeh PY , Lu YS , Hsu CH , Chen KF , Lee WC , et al . OSU-03012, a novel celecoxib derivative, induces reactive oxygen species-related autophagy in hepatocellular carcinoma . Cancer Res . 2008 ; 68 ( 22 ): 9348 - 57 .

Gao Y , Cai A , Xi H , Li J , Xu W , Zhang Y , et al . Ring finger protein 43 associates with gastric cancer progression and attenuates the stemness of gastric cancer stem-like cells via the Wnt-β/catenin signaling pathway . Stem Cell Res Ther . 2017 ; 8 ( 1 ): 98 .

Bauer C , Duewell P , Mayer C , Lehr HA , Fitzgerald KA , Dauer M , et al . Colitis induced in mice with dextran sulfate sodium (DSS) is mediated by the NLRP3 inflammasome . Gut . 2010 ; 59 ( 9 ): 1192 - 9 .

Turpin W , Lee SH , Raygoza Garay JAR , Madsen KL , Meddings JB , Bedrani L , et al . Increased intestinal permeability is associated with later development of Crohn’s disease . Gastroenterology . 2020 ; 159 ( 6 ): 2092-100.e5 .

Sinha SR , Haileselassie Y , Nguyen LP , Tropini C , Wang M , Becker LS , et al . Dysbiosis-induced secondary bile acid deficiency promotes intestinal inflammation . Cell Host Microbe . 2020 ; 27 ( 4 ): 659-70.e5 .

Wu H , Xie S , Miao J , Li Y , Wang Z , Wang M , et al . Lactobacillus reuteri maintains intestinal epithelial regeneration and repairs damaged intestinal mucosa . Gut Microbes . 2020 ; 11 ( 4 ): 997 - 1014 .

Shimokawa C , Kato T , Takeuchi T , Ohshima N , Furuki T , Ohtsu Y , et al . CD8 + regulatory T cells are critical in prevention of autoimmune-mediated diabetes . Nat Commun . 2020 ; 11 ( 1 ): 1922 .

Mattock E , Blocker AJ . How do the virulence factors of Shigella work together to cause disease? Front Cell Infect Microbiol . 2017 ; 7 : 64 .

Zamani S , Taslimi R , Sarabi A , Jasemi S , Sechi LA , Feizabadi MM . Enterotoxigenic Bacteroides fragilis: a possible etiological candidate for bacteriallyinduced colorectal precancerous and cancerous lesions . Front Cell Infect Microbiol . 2019 ; 9 : 449 .

Liu H , Zhu J , Hu Q , Rao X . Morganella morganii, a non-negligent opportunistic pathogen . Int J Infect Dis . 2016 ; 50 : 10 - 7 .

Barnett MPG , McNabb WC , Cookson AL , Zhu S , Davy M , Knoch B , et al . Changes in colon gene expression associated with increased colon inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus species . BMC Immunol . 2010 ; 11 : 39 .

Guo H , Chou WC , Lai Y , Liang K , Tam JW , Brickey WJ , et al . Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites . Science . 2020 ; 370 ( 6516 ): eaay9097 .

Franzosa EA , Sirota-Madi A , Avila-Pacheco J , Fornelos N , Haiser HJ , Reinker S , et al . Gut microbiome structure and metabolic activity in inflammatory bowel disease . Nat Microbiol . 2019 ; 4 ( 2 ): 293 - 305 .

Duan C , Kuang L , Xiang X , Zhang J , Zhu Y , Wu Y , et al . Activated Drp1-mediated mitochondrial ROS influence the gut microbiome and intestinal barrier after hemorrhagic shock . Aging (Albany N Y) . 2020 ; 12 ( 2 ): 1397 - 416 .

Alam A , Leoni G , Quiros M , Wu H , Desai C , Nishio H , et al . The microenvironment of injured murine gut elicits a local pro-restitutive microbiota . Nat Microbiol . 2016 ; 1 : 15021 .

He S , Guo Y , Zhao J , Xu X , Song J , Wang N , et al . Ferulic acid protects against heat stress-induced intestinal epithelial barrier dysfunction in IEC-6 cells via the PI3K/Akt-mediated Nrf2/HO-1 signaling pathway . Int J Hyperthermia . 2019 ; 35 ( 1 ): 112 - 21 .

Zhuang Y , Wu H , Wang X , He J , He S , Yin Y . Resveratrol attenuates oxidative stress-induced intestinal barrier injury through PI3K/Akt-mediated Nrf2 signaling pathway . Oxid Med Cell Longev . 2019 ; 2019 : 7591840 .

Lee H , Son YS , Lee MO , Ryu JW , Park K , Kwon O , et al . Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways . Theranostics . 2020 ; 10 ( 11 ): 5048 - 63 .

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