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Comparison of five diarrhea-predominant irritable bowel syndrome (IBS-D) rat models in the brain-gut-microbiota axis - 20/04/22

Doi : 10.1016/j.biopha.2022.112811 
Haomeng Wu a, b, c, d, 1, Kai Zhan b, 1, Kehan Rao b, 1, Huan Zheng b, d, Shumin Qin b, c, d, Xudong Tang a, , Shaogang Huang b, c, d, e,
a Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China 
b The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China 
c State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China 
d Collaborative Innovation Team of Traditional Chinese Medicine in Prevention and Treatment of Functional Gastrointestinal Diseases, Guangzhou 510120, China 
e Dongguan Hospital of Guangzhou University of Chinese Medicine, Dongguan 523000, China 

Corresponding author.⁎⁎Corresponding author at: The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.The Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou510120China

Abstract

The brain-gut-microbiota (BGM) axis is known to be essential for diarrhea-predominant irritable bowel syndrome (IBS-D). In order to evaluate the effects of IBS-D rat models (the central sensitization model, the peripheral sensitization model and the compound model) on the BGM axis, five models were induced in Wistar rats with 4% acetic acid (AD, dissolved 0.4 ml of AD in 9.6 ml of ultrapure water) + wrap restrain stress (WRS), 4% AD, colorectal distention (CRD), WRS, and neonatal maternal separation (NMS). Abdominal withdrawal reflex (AWR) scale scores and the moisture content of feces (MCF) were evaluated on the day of completing modeling. Body weight was measured every 7 days during modeling. Brain gut peptides, cytokine levels, the activity of spinal cord neurons, intestinal mucosal barrier function, and gut microbiota were determined after induction of IBS-D. We found intervention with 4% AD + WRS, 4% AD, CRD, WRS, and NMS induced a similar course of effects on the BGM axis. Among the five models, AWR scores (60 mmHg, 80 mmHg) were all increased. The levels of 5-hydroxytryptamine, corticotropin-releasing factor, substance P, and calcitonin gene-related protein in serum rapidly increased, whereas that of neuropeptide Y decreased. C-fos in the spinal cord showed increased neuronal activity. The intestinal permeability was increased and the composition and structure of gut microbiota were changed. In conclusion, the five models could cause changes in BGM axis, but the 4% AD + WRS model was closer to the changes BGM axis of post-inflammatory models of IBS-D.

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Highlights

The five IBS-D rat models had similar imbalances of the brain-gut-microbiota axis and similar measurable outcomes.
4% AD + WRS rat model was closer to the changes brain-gut-microbiota axis of post-inflammatory models of IBS-D.
The brain gut interaction induced by the 4% AD + WRS rat model is not dominant from the change of brain gut peptide alone.
The models induced by 4% AD + WRS and WRS may be easier to observe the alteration of gut microbiota involved in IBS-D.

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Abbreviations : IBS-D, BGM, AWR, CRF, CGRP, NPY, AD, WRS, NMS, CRD, MS, NNC, MCF, TNBS, VH, CNS, F-B ratio

Keywords : Diarrhea predominant-irritable bowel syndrome, Brain-gut-microbiota axis, Rat models, Acetic acid, Wrap restrain stress, Colorectal distention, Neonatal maternal separation


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