Influence of intestinal flora on serum inflammatory factors in patients with chronic urticaria

doi:10.3969/j.issn.1673-8640.2021.05.009

Abstract

Abstract:

Objective To investigate the influence of intestinal flora on serum inflammatory factors in patients with chronic urticaria. Methods Totally,60 patients with chronic urticaria and 60 healthy subjects were enrolled,and fasting venous blood and stool samples were collected. Gene 16S rDNA real-time fluorescence quantitative polymerase chain reaction（PCR） was used to determine the levels of Faecalibacterium prausnitzii,Clostridium leptum,Bifidobacterium and Lactobacillus. Gas chromatography was used to determine intestinal short chain fatty acid. Serum Toll-like receptor 4（TLR4）,nuclear factor（NF）-κB,tumor necrosis factor-alpha（TNF-α） and interleukin-6（IL-6） were determined by enzyme-linked immunosorbent assay（ELISA）. Spearman correlation analysis was used to analyze the relationship between intestinal flora,short chain fatty acid and serum TLR4,NF-κB,TNF-α and IL-6. Results Compared with the control group,the levels of Faecalibacterium prausnitzii,Clostridium leptum,Lactobacillus and butyric acid in the intestine of patients with chronic urticaria were decreased（P<0.05）. Serum TLR4,NF-κB,TNF-α and IL-6 levels were increased（P<0.05）. Correlation analysis showed that Faecalibacterium prausnitzii,Clostridium leptum,Lactobacillus and butyric acid were negatively correlated with serum TLR4,NF-κB,TNF-α and IL-6（P<0.05）. Conclusions The increase of serum inflammatory factors in patients with chronic urticaria may be related to the decrease of intestinal butyric acid-producing bacteria,leading to a decrease in intestinal butyric acid levels and up-regulation of TLR4/NF-κB signaling pathway.

Key words: Intestinal flora, Short chain fatty acid, Toll-like receptor 4, Tumor necrosis factor-alpha, Interleukin-6, Chronic urticaria

CLC Number:

R446.5

REN Yuan, ZHANG Min, YIN Xiang, ZENG Qianwen. Influence of intestinal flora on serum inflammatory factors in patients with chronic urticaria[J]. Laboratory Medicine, 2021, 36(5): 504-509.

Figures/Tables 5

References 25

[1]	BAIOUMY S A, ESAWY M M, SHABANA M A. Assessment of circulating FCεRIa in chronic spontaneous urticaria patients and its correlation with clinical and immunological variables[J]. Immunobiology, 2018,223(12):807-811. DOI URL
[2]	LU T, CHEN Y, GUO Y, et al. Altered gut microbiota diversity and composition in chronic urticaria[J]. Dis Markers, 2019,2019:6417471.
[3]	李琳琳, 杨浩, 王烨. 肠道菌群代谢产物短链脂肪酸与2型糖尿病的关系[J]. 新疆医科大学学报, 2017,40(12):1517-1521.
[4]	TRINH H K, PHAM D L, BAN G Y, et al. Altered systemic adipokines in patients with chronic urticaria[J]. Int Arch Allergy Immunol, 2016,171(2):102-110. DOI URL
[5]	ATWA M A, EMARA A S, YOUSSEF N, et al. Serum concentration of IL-17,IL-23 and TNF-α among patients with chronic spontaneous urticaria:association with disease activity and autologous serum skin test[J]. J Eur Acad Dermatol Venereol, 2014,28(4):469-474. DOI URL
[6]	周雪峰, 陆其明. 微生态制剂治疗缺血性肠炎的疗效观察[J]. 预防医学, 2017,29(12):1256-1257.
[7]	杨浩, 王烨, 王蟾月, 等. 新疆维吾尔族2型糖尿病人群肠道中Faecalibacterium prausnitzii的定量研究[J]. 中国微生态学杂志, 2017,29(9):1005-1008.
[8]	AMINI-KHOEI H, HAGHANI-SAMANI E, BEIGI M, et al. On the role of corticosterone in behavioral disorders,microbiota composition alteration and neuroimmune response in adult male mice subjected to maternal separation stress[J]. Int Immunopharmacol, 2019,66:242-250. DOI URL
[9]	NABIZADEH E, JAZANI N H, BAGHERI M, et al. Association of altered gut microbiota composition with chronic urticaria[J]. Ann Allergy Asthma Immunol, 2017,119(1):48-53. DOI URL
[10]	REZAZADEH A, SHAHABI S, BAGHERI M, et al. The protective effect of Lactobacillus and Bifidobacterium as the gut microbiota members against chronic urticaria[J]. Int Immunopharmacol, 2018,59:168-173. DOI URL
[11]	WANG D, GUO S, HE H, et al. Gut microbiome and serum metabolome analyses identify unsaturated fatty acids and butanoate metabolism induced by gut microbiota in patients with chronic spontaneous urticaria[J]. Front Cell Infect Microbiol, 2020,10:24. DOI URL
[12]	XU J, LIANG R, ZHANG W, et al. Faecalibacterium prausnitzii-derived microbial anti-inflammatory molecule regulates intestinal integrity in diabetes mellitus mice via modulating tight junction protein expression[J]. J Diabetes, 2020,12(3):224-236. DOI URL
[13]	BYNDLOSS M X, OLSAN E E, RIVERA-CHÁVEZ F, et al. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion[J]. Science, 2017,357(6351):570-575. DOI URL
[14]	MANRIQUE VERGARA D, GONZÁLEZ SÁNCHEZ M E. Short chain fatty acids(butyric acid) and intestinal diseases[J]. Nutr Hosp, 2017,34(Suppl 4):58-61.
[15]	陈兆桂, 于成功. Faecalibacterium prausnitzii对实验性结肠炎中TLR4/NF-κB信号通路的影响[J]. 胃肠病学, 2016,21(11):644-649.
[16]	NI W W, ZHANG Q M, ZHANG X, et al. Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in β-lactoglobulin-induced allergic mice model[J]. Allergol Immunopathol(Madr), 2020,8(2):149-157.
[17]	SETH R K, KIMONO D, ALHASSON F, et al. Increased butyrate priming in the gut stalls microbiome associated-gastrointestinal inflammation and hepatic metabolic reprogramming in a mouse model of Gulf War Illness[J]. Toxicol Appl Pharmacol, 2018,350:64-77. DOI URL
[18]	JI X, ZHANG X, LI H, et al. Nfa34810 facilitates Nocardia farcinica invasion of host cells and stimulates tumor necrosis factor alpha secretion through activation of the NF-κB and mitogen-activated protein kinase pathways via Toll-like receptor 4[J]. Infect Immun, 2020,8(4):e00831-19.
[19]	KRASOVSKA V, DOERING L C. Regulation of IL-6 secretion by astrocytes via TLR4 in the fragile X mouse model[J]. Front Mol Neurosci, 2018,11:272. DOI URL
[20]	DE MONTJOYE L, CHOTEAU M, HERMAN A, et al. IL-6 and IL-1β expression is increased in autologous serum skin test of patients with chronic spontaneous urticaria[J]. Allergy, 2019,74(12):2522-2524. DOI URL
[21]	SHARMA P, SHARMA P K, CHITKARA A, et al. To evaluate the role and relevance of cytokines IL-17,IL-18,IL-23 and TNF-α and their correlation with disease severity in chronic urticaria[J]. Indian Dermatol Online J, 2020,11(4):594-597.
[22]	SAND F L, THOMSEN S F. Off-label use of TNF-alpha inhibitors in a dermatological university department:retrospective evaluation of 118 patients[J]. Dermatol Ther, 2015,28(3):158-165. DOI URL
[23]	KOLKHIR P, ALTRICHTER S, MUNOZ M, et al. New treatments for chronic urticaria[J]. Ann Allergy Asthma Immunol, 2020,124(1):2-12. DOI URL
[24]	DEZA G, RICKETTI P A, GIMÉNEZ-ARNAU A M, et al. Emerging biomarkers and therapeutic pipelines for chronic spontaneous urticaria[J]. J Allergy Clin Immunol Pract, 2018,6(4):1108-1117. DOI URL
[25]	NETTIS E, LEO E D, PASTORE A, et al. Probiotics and refractory chronic spontaneous urticaria[J]. Ann Allergy Clin Immunol, 2016,48(5):182-187.

指标	TLR4		NF-κB		TNF-α		IL-6
指标	r值	P值	r值	P值	r值	P值	r值	P值
普拉梭菌	-0.813	0.004	-0.773	0.009	-0.721	0.019	-0.705	0.023
柔嫩梭菌	-0.650	0.042	-0.749	0.013	-0.787	0.007	-0.698	0.025
双歧杆菌	0.214	0.553	0.140	0.699	-0.061	0.868	0.041	0.911
乳酸杆菌	-0.724	0.018	-0.648	0.043	-0.620	0.056	-0.727	0.017
乙酸	0.019	0.959	-0.104	0.774	-0.328	0.356	-0.396	0.257
丙酸	-0.246	0.494	-0.159	0.662	-0.024	0.948	0.273	0.445
丁酸	-0.739	0.015	-0.876	0.001	-0.661	0.038	-0.760	0.011

指标	TLR4		NF-κB		TNF-α		IL-6
指标	r值	P值	r值	P值	r值	P值	r值	P值
普拉梭菌	-0.813	0.004	-0.773	0.009	-0.721	0.019	-0.705	0.023
柔嫩梭菌	-0.650	0.042	-0.749	0.013	-0.787	0.007	-0.698	0.025
双歧杆菌	0.214	0.553	0.140	0.699	-0.061	0.868	0.041	0.911
乳酸杆菌	-0.724	0.018	-0.648	0.043	-0.620	0.056	-0.727	0.017
乙酸	0.019	0.959	-0.104	0.774	-0.328	0.356	-0.396	0.257
丙酸	-0.246	0.494	-0.159	0.662	-0.024	0.948	0.273	0.445
丁酸	-0.739	0.015	-0.876	0.001	-0.661	0.038	-0.760	0.011

变量	β值	标准误	Wald值	P值	OR值	95%可信区间
普拉梭菌	-2.085	0.730	8.165	0.004	0.124	0.030~0.520
柔嫩梭菌	-1.886	0.772	5.962	0.015	0.152	0.033~0.689
双歧杆菌	0.499	0.748	0.446	0.504	1.648	0.381~7.131
乳酸杆菌	-2.260	0.970	5.430	0.020	0.104	0.016~0.698
乙酸	-0.023	0.023	0.977	0.323	0.978	0.935~1.022
丙酸	-0.165	0.111	2.217	0.136	0.848	0.683~1.053
丁酸	-0.304	0.127	5.733	0.017	0.738	0.575~0.946

变量	β值	标准误	Wald值	P值	OR值	95%可信区间
普拉梭菌	-2.085	0.730	8.165	0.004	0.124	0.030~0.520
柔嫩梭菌	-1.886	0.772	5.962	0.015	0.152	0.033~0.689
双歧杆菌	0.499	0.748	0.446	0.504	1.648	0.381~7.131
乳酸杆菌	-2.260	0.970	5.430	0.020	0.104	0.016~0.698
乙酸	-0.023	0.023	0.977	0.323	0.978	0.935~1.022
丙酸	-0.165	0.111	2.217	0.136	0.848	0.683~1.053
丁酸	-0.304	0.127	5.733	0.017	0.738	0.575~0.946