Correlation study between high altitude IBS and intestinal barrier damage, inflammatory mediators and neurotransmitters

doi:10.11958/20230882

Abstract

Abstract:

Objective To analyzing changes of indicators related to intestinal barrier damage, neurotransmitters and inflammatory mediators in patients with irritable bowel syndrome (IBS) in the plateau environment, and explore the underlying pathogenesis of IBS. Methods A prospective cohort observation was conducted on 81 healthy male Han Chinese volunteers who were admitted to Lhasa of Tibe from plain. The study lasted for one year. During the one-year follow-up, 13 patients who developed IBS (Rome Ⅳ) were selected as the study subjects. Additionally 11 participants who remained healthy were randomly selected as the control group (named NC). Eleven participants who entered Lhasa from plain within one week and did not develop acute mountain sickness were randomly selected as the NC early group. Serum levels of diamine oxidase (DAO) and intestinal fatty acid-binding protein (I-FABP), 5-hydroxytryptamine (5-HT), interleukin (IL)-6, IL-17A and lipopolysaccharide (LPS) were measured using enzyme-linked immunosorbent assay (ELISA). At the end of the follow-up period, colonoscopy and intestinal mucosal biopsy were performed in 9 cases of IBS, while colonoscopy was performed in 4 cases of NC. Results Colonoscopy and pathological results of IBS patients in plateau environment suggested mild inflammation of intestinal mucosa. Compared to the NC early group, the NC group showed increased levels of 5-HT, DAO, I-FABP, IL-6, IL-17A and LPS at 3 months after entering Lassa, and increased levels of 5-HT, I-FABP, IL-6, and LPS at 6 months (P<0.05). Compared with the NC group, the IBS group showed decreased levels of 5-HT and LPS at 3 months after entering Lhasa (P<0.05). Serological indexes of NC group at 6 months were lower than those at 3 months in the NC group (P<0.05). There were no significant differences in serological indexes at 3 and 6 months of the IBS group. Conclusion Indicators of intestinal mucosal barrier damage, neurotransmitters and inflammatory mediators might be involved in the development of IBS in plateau environment.

Key words: irritable bowel syndrome, serotonin, fatty acid-binding proteins, interleukin 6, plateau environment

CLC Number:

R574.4

Figures/Tables 4

Tab.1 Comparison of baseline characteristics between three groups

组别	n	年龄/岁	BMI/（kg/m²）	学历（大专以下/大专及以上）	睡眠/h
NC早期组	11	19.73±1.27	23.33±3.11	3/8	8.64±0.55
NC组	11	20.09±1.22	22.19±2.33	4/7	8.00±0.71^a
IBS组	13	20.23±1.48	21.44±1.32	6/7	8.15±0.55^a
F或χ²		0.438	1.995	0.923	3.337^＊

Fig.1 Colonoscopic mucosal manifestations between the IBS group and the NC group at the last follow-up

Fig.2 HE staining of intestinal mucosa in patients with IBS (×100)

Tab.2 Comparison of serological parameters at different time points in plateau environment between three groups

References 30

[1]	ZHANG X G, XU W, ZHONG W L, et al. Exploring the links between gut microbiome changes and irritable bowel syndrome in Han populations in the Tibetan Plateau[J]. J Zhejiang Univ Sci B, 2023, 24(9):823-838. doi:10.1631/jzus.B2200509.
[2]	CHENG J F, SUN Y M, HE J X, et al. The mechanism of colon tissue damage mediated by HIF-1alpha/NF-kappaB/STAT1 in high-altitude environment[J]. Front Physiol, 2022, 13:933659. doi:10.3389/fphys.2022.933659.
[3]	WANG Y H, SHI Y, LI W H, et al. Gut microbiota imbalance mediates intestinal barrier damage in high-altitude exposed mice[J]. FEBS J, 2022, 289(16):4850-4868. doi:10.1111/febs.16409.
[4]	LI Y Y, WANG Y C, SHI F, et al. Phospholipid metabolites of the gut microbiota promote hypoxia-induced intestinal injury via CD1d-dependent γδ T cells[J]. Gut Microbes, 2022, 14(1):2096994. doi:10.1080/19490976.2022.2096994.
[5]	CALDERWOOD A H, SCHROY P C 3RD, LIEBERMAN D A, et al. Boston Bowel Preparation Scale scores provide a standardized definition of adequate for describing bowel cleanliness[J]. Gastrointest Endosc, 2014, 80(2):269-276. doi:10.1016/j.gie.2014.01.031.
[6]	邢征, 张根苗, 金志, 等. 高原地区炎症性肠病124例调查分析[J]. 临床消化病杂志, 2009, 21(4):245-246.
	XING Z, ZHANG G M, JIN Z, et al. Investigation and analysis of 124 cases of inflammatory bowel disease in plateau area[J]. Journal of Clinical Gastroenterology, 2019, 21(4):245-246. doi:1005-541X(2009)04-245-02.
[7]	李易, 韩盛玺. 肠易激综合征的结肠镜下表现[J]. 中国内镜杂志, 2008, 14(6):628-629.
	LI Y, HAN S X. Manifestation of irritable bowel syndrome under colonscope[J]. China Journal of Endoscopy, 2008, 14(6):628-629. doi:1007-1989(2008)06-0628-02.
[8]	颜君, 周国华, 余细球, 等. 肠易激综合征与结肠慢性炎症的相关性研究[J]. 中国实用医药, 2017, 12(8):47-49.
	YAN J, ZHOU G H, YU X Q, et al. Study on correlation between irritable bowel syndrome and colon chronic inflammation[J]. China Prac Med, 2017, 12(8):47-49. doi:10.14163/j.cnki.11-5547/r.2017.08.019.
[9]	FUKUI H. Increased intestinal permeability and decreased barrier function:does it really influence the risk of inflammation?[J]. Inflamm Intest Dis, 2016, 1(3):135-145. doi:10.1159/000447252.
[10]	KLEM F, WADHWA A, PROKOP L J, et al. Prevalence,risk factors,and outcomes of irritable bowel syndrome after infectious enteritis:a systematic review and meta-analysis[J]. Gastroenterology, 2017, 152(5):1042-1054.e1. doi:10.1053/j.gastro.2016.12.039.
[11]	王晓辉, 崔立红, 闫志辉, 等. 肠道感染病史及药物因素对肠易激综合征发病的影响[J]. 解放军医药杂志, 2014, 26(2):30-33.
	WANG X H, CUI L H, YAN Z H, et al. Effect of intestinal infection history and drug use factors on irritable bowel syndrome[J]. Med ＆ Pharm J Chin PLA, 2014, 26(2):30-33. doi:10.3969/j.issn.2095-140X.2014.02.010.
[12]	MARSHALL J K, THABANE M, GARG A X, et al. Eight year prognosis of postinfectious irritable bowel syndrome following waterborne bacterial dysentery[J]. Gut, 2010, 59(5):605-611. doi:10.1136/gut.2009.202234.
[13]	王子恺, 杨云生. 感染后肠易激综合征[J]. 胃肠病学和肝病学杂志, 2012, 21(10):966-970.
	WANG Z K, YANG Y S. Post-infectious irritable bowel syndrome[J]. Chin J Gastroenterol Hepatol, 2012, 21(10):966-970. doi:10.3969/j.issn.1006-5709.2012.10.026.
[14]	李榕娇, 郭维龙, 孙慧冰, 等. 肠易激综合征患者肠道菌群分布和炎症因子及血清NPY、SP、5-HT水平的变化[J]. 中国微生态学杂志, 2020, 32(9):1060-1064.
	LI R J, GUO W L, SUN H B, et al. The distribution of intestinal flora,levels of inflammatory factors and serum NPY,SP and 5-HT in patients with irritable bowel syndrome[J]. Chin J Microecol, 2020, 32(9):1060-1064. doi:10.13381/J.cnki.cjm.202009014.
[15]	代迎欢, 蓝程, 刘丹, 等. 感染后肠易激综合征患者临床特征和细胞因子的表达[J]. 中山大学学报(医学科学版), 2017, 38(2):260-266.
	DAI Y H, LAN C, LIU D, et al. Clinical features and expression of cytokine in post-infectious irritable bowel syndrome patients[J]. Journal of Sun Yat-Sen University(Medical Sciences), 2017, 38(2):260-266. doi:10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2017.0042.
[16]	BERG L K, GOLL R, FAGERLI E, et al. Intestinal inflammatory profile shows increase in a diversity of biomarkers in irritable bowel syndrome[J]. Scand J Gastroenterol, 2020, 55(5):537-542. doi:10.1080/00365521.2020.1754455.
[17]	YANG B, ZHOU X C, LAN C. Changes of cytokine levels in a mouse model of post-infectious irritable bowel syndrome[J]. BMC Gastroenterol, 2015, 15:43. doi:10.1186/s12876-015-0272-8.
[18]	陈思琪, 朱焰, 陈敏. 基于国家专利的中药复方治疗肠易激综合征用药规律及核心处方作用机制研究[J]. 中国中西医结合外科杂志, 2023, 29(2):197-203.
	CHEN S Q, ZHU Y, CHEN M. Study on the medication rule and mechanism of core prescription of Chinese herbal compound in the treatment of irritable bowel syndrome based on patent database[J]. Chinese Journal of Surgery of Integrated Traditional and Western Medicine, 2023, 29(2):197-203. doi:10.3969/j.issn.1007-6948.2023.02.012.
[19]	ZHU S, QIAN Y C. IL-17/IL-17 receptor system in autoimmune disease:mechanisms and therapeutic potential[J]. Clin Sci (Lond), 2012, 122(11):487-511. doi:10.1042/CS20110496.
[20]	LIEBREGTS T, ADAM B, BREDACK C, et al. Immune activation in patients with irritable bowel syndrome[J]. Gastroenterology, 2007, 132(3):913-920. doi:10.1053/j.gastro.2007.01.046.
[21]	SCHELLEKENS D H, GROOTJANS J, DELLO S A, et al. Plasma intestinal fatty acid-binding protein levels correlate with morphologic epithelial intestinal damage in a human translational ischemia-reperfusion model[J]. J Clin Gastroenterol, 2014, 48(3):253-260. doi:10.1097/MCG.0b013e3182a87e3e.
[22]	张梦, 陈超英, 胡玥, 等. 黏附连接及紧密连接与腹泻型肠易激综合征症状之间的关系[J]. 中华内科杂志, 2020, 59(1):40-46.
	ZHANG M, CHEN C Y, HU Y, et al. The relationship between adherens junction and tight junction and clinical symptoms in patients with diarrhea predominant irritable bowel syndrome[J]. Chin J Intern Med, 2020, 59(1):40-46. doi:10.3760/cma.j.issn.0578-1426.2020.01.007.
[23]	GONZALEZ-CASTRO A M, MARTINEZ C, SALVO-ROMERO E, et al. Mucosal pathobiology and molecular signature of epithelial barrier dysfunction in the small intestine in irritable bowel syndrome[J]. J Gastroenterol Hepatol, 2017, 32(1):53-63. doi:10.1111/jgh.13417.
[24]	WANG J B, LU S H, ZHAO S J. Post-infectious and non post-infectious irritable bowel syndrome:a comparative study[J]. Pak J Med Sci, 2016, 32(1):116-119. doi:10.12669/pjms.321.8628.
[25]	杨敏, 程雁. 血清二胺氧化酶和肠脂肪酸结合蛋白测定评价窒息新生儿胃肠功能障碍的临床研究[J]. 中国临床药理学杂志, 2022, 38(23):2803-2806.
	YANG M, CHENG Y. Clinical trial of serum diamine oxidase and intestinal fatty acid binding protein in evaluating gastrointestinal dysfunction in neonates with asphyxia[J]. Chin J Clin Pharmacol, 2022, 38(23):2803-2806. doi:10.13699/j.cnki.1001-6821.2022.23.003.
[26]	JI M, HUANG H, LAN X M. Correlation between intestinal microflora in irritable bowel syndrome and severity[J]. Dis Markers, 2022, 2022:1031844. doi:10.1155/2022/1031844.
[27]	MISHIMA Y, ISHIHARA S. Enteric microbiota-mediated serotonergic signaling in pathogenesis of irritable bowel syndrome[J]. Int J Mol Sci, 2021, 22(19):10235. doi:10.3390/ijms221910235.
[28]	NG Q X, SOH A Y S, LOKE W, et al. The role of inflammation in irritable bowel syndrome (IBS)[J]. J Inflamm Res, 2018, 11:345-349. doi:10.2147/JIR.S174982.
[29]	GAO J, XIONG T T, GRABAUSKAS G, et al. Mucosal serotonin reuptake transporter expression in irritable bowel syndrome is modulated by gut microbiota via mast cell-prostaglandin E2[J]. Gastroenterology, 2022, 162(7):1962. doi:10.1053/j.gastro.2022.02.016.
[30]	QIN H Y, CHENG C W, TANG X D, et al. Impact of psychological stress on irritable bowel syndrome[J]. World J Gastroenterol, 2014, 20(39):14126-14131. doi:10.3748/wjg.v20.i39.14126.