Study on the Clinical Mechanism of Tong-Xie-An-Chang Decoction in the Treatment of Diarrheal Irritable Bowel Syndrome Based on Single-cell Sequencing Technology

Overview

Journal Medicine (Baltimore)

Specialty General Medicine

Date 2020 Dec 22

PMID 33350782

Citations 2

Authors

Xiang Tan

Xing-Jie Zhao

Jun-Xiang Li

Chun-E Xie

Wen-Jing Pei

Lei Shi

Fu-Shun Kou

Ya-Li Yuan

Xiao-Xuan Xue

Affiliations

Soon will be listed here.

Abstract

Background: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a kind of functional gastrointestinal disorder with obscure pathogenesis, and exploration about differential gene expression and cell heterogeneity of T lymphocytes in peripheral blood in IBS-D patients still remains unknown. Clinicians tend to use symptomatic treatment, but the efficacy is unstable and symptoms are prone to relapse. Traditional Chinese Medicine (TCM) is used frequently in IBS-D with stable and lower adverse effects. Tong-Xie-An-Chang Decoction (TXACD) has been proven to be effective in the treatment of IBS-D. However, the underlying therapeutic mechanism remains unclear. This trial aims to evaluate the clinical efficacy and safety of TXACD in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXACD based on single-cell sequencing technology.

Methods/design: This is a randomized controlled, double-blind, double-simulation clinical trial in which 72 eligible participants with IBS-D and TCM syndrome of liver depression and spleen deficiency will be randomly allocated in the ratio of 1:1 to two groups: the experimental group and the control group. The experimental group receives Tong-Xie-An-Chang Decoction (TXACD) and Pinaverium bromide tablets placebo; the control group receives pinaverium bromide tablets and TXACD placebo. Each group will be treated for 4 weeks. The primary outcome: the rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes: TCM syndrome score, adequate relief and IBS-Quality of Life Questionnaire (IBS-QOL). Mechanistic outcome is the single-cell sequencing profiling of the T lymphocytes in peripheral blood from IBS-D participants before and after the treatment and healthy individuals.

Discussion: This trial will prove the efficacy and safety of TXACD with high-quality evidence and provide a comprehensive perspective on the molecular mechanism of IBS-D by single-cell sequencing profiling, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXACD.

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References

Guo Y, Li J, Wang Y, Mao T, Chen C, Xie T . Yinchen Linggui Zhugan Decoction Ameliorates Nonalcoholic Fatty Liver Disease in Rats by Regulating the Nrf2/ARE Signaling Pathway. Evid Based Complement Alternat Med. 2017; 2017:6178358. PMC: 5592414. DOI: 10.1155/2017/6178358. View

Wang Y, Huang Y, Zhu S, Zhang C, Chen X, Hou Q . Efficacy of Tong-Xie-Yao-Fang granule and its impact on whole transcriptome profiling in diarrhea-predominant irritable bowel syndrome patients: study protocol for a randomized controlled trial. Trials. 2020; 21(1):908. PMC: 7607547. DOI: 10.1186/s13063-020-04833-x. View

Hauser G, Tkalcic M, Pletikosic S, Grabar N, Stimac D . Erythrocyte sedimentation rate - possible role in determining the existence of the low grade inflammation in Irritable Bowel Syndrome patients. Med Hypotheses. 2012; 78(6):818-20. DOI: 10.1016/j.mehy.2012.03.020. View

Wong H, Qin H, Tsang S, Zuo X, Che S, Chow C . Early life stress disrupts intestinal homeostasis via NGF-TrkA signaling. Nat Commun. 2019; 10(1):1745. PMC: 6465335. DOI: 10.1038/s41467-019-09744-3. View

Djebali S, Davis C, Merkel A, Dobin A, Lassmann T, Mortazavi A . Landscape of transcription in human cells. Nature. 2012; 489(7414):101-8. PMC: 3684276. DOI: 10.1038/nature11233. View

Chadwick V, Chen W, Shu D, Paulus B, Bethwaite P, Tie A . Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002; 122(7):1778-83. DOI: 10.1053/gast.2002.33579. View

Ohman L, Simren M . New insights into the pathogenesis and pathophysiology of irritable bowel syndrome. Dig Liver Dis. 2007; 39(3):201-15. DOI: 10.1016/j.dld.2006.10.014. View

Longstreth G, Grant Thompson W, Chey W, Houghton L, Mearin F, Spiller R . Functional bowel disorders. Gastroenterology. 2006; 130(5):1480-91. DOI: 10.1053/j.gastro.2005.11.061. View

Rana S, Sharma S, Sinha S, Parsad K, Malik A, Singh K . Pro-inflammatory and anti-inflammatory cytokine response in diarrhoea-predominant irritable bowel syndrome patients. Trop Gastroenterol. 2013; 33(4):251-6. DOI: 10.7869/tg.2012.66. View

10.

Hungin A, Chang L, Locke G, Dennis E, Barghout V . Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Aliment Pharmacol Ther. 2005; 21(11):1365-75. DOI: 10.1111/j.1365-2036.2005.02463.x. View

11.

Francis C, Morris J, Whorwell P . The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther. 1997; 11(2):395-402. DOI: 10.1046/j.1365-2036.1997.142318000.x. View

12.

Fu R, Chen M, Chen Y, Mao G, Liu S . Expression and clinical significance of 5-HT and 5-HTR in the intestinal mucosa of patient with diarrhea-type irritable bowel syndrome. Exp Ther Med. 2019; 17(4):3077-3082. PMC: 6434247. DOI: 10.3892/etm.2019.7297. View

13.

Drossman D . Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016; . DOI: 10.1053/j.gastro.2016.02.032. View

14.

Sundin J, Aziz I, Nordlander S, Polster A, Hu Y, Hugerth L . Evidence of altered mucosa-associated and fecal microbiota composition in patients with Irritable Bowel Syndrome. Sci Rep. 2020; 10(1):593. PMC: 6969101. DOI: 10.1038/s41598-020-57468-y. View

15.

Moloney R, Johnson A, OMahony S, Dinan T, Greenwood-Van Meerveld B, Cryan J . Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome. CNS Neurosci Ther. 2015; 22(2):102-17. PMC: 6492884. DOI: 10.1111/cns.12490. View

16.

Moloney R, OMahony S, Dinan T, Cryan J . Stress-induced visceral pain: toward animal models of irritable-bowel syndrome and associated comorbidities. Front Psychiatry. 2015; 6:15. PMC: 4329736. DOI: 10.3389/fpsyt.2015.00015. View

17.

Cremon C, Gargano L, Morselli-Labate A, Santini D, Cogliandro R, De Giorgio R . Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms. Am J Gastroenterol. 2009; 104(2):392-400. DOI: 10.1038/ajg.2008.94. View

18.

Cash B, Pimentel M, Rao S, Weinstock L, Chang L, Heimanson Z . Repeat treatment with rifaximin improves irritable bowel syndrome-related quality of life: a secondary analysis of a randomized, double-blind, placebo-controlled trial. Therap Adv Gastroenterol. 2017; 10(9):689-699. PMC: 5598815. DOI: 10.1177/1756283X17726087. View

19.

Pan F, Zhang T, Zhang Y, Xu J, Chen F . Effect of Tongxie Yaofang Granule in treating diarrhea-predominate irritable bowel syndrome. Chin J Integr Med. 2009; 15(3):216-9. DOI: 10.1007/s11655-009-0216-7. View

20.

Marshall J, Thabane M, Garg A, Clark W, Meddings J, Collins S . Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario. Aliment Pharmacol Ther. 2004; 20(11-12):1317-22. DOI: 10.1111/j.1365-2036.2004.02284.x. View