无症状高尿酸血症患者小肠细菌过度生长及炎症细胞因子表达水平

温倩颖; 张丽卿; 秦安霖; 李小峰

doi:10.19723/j.issn.1671-167X.2026.02.014

北京大学学报（医学版） >

2026 , Vol. 58 >Issue 2: 313 - 318

DOI: https://doi.org/10.19723/j.issn.1671-167X.2026.02.014

论著

无症状高尿酸血症患者小肠细菌过度生长及炎症细胞因子表达水平

温倩颖 ¹^,² ,
张丽卿 ^,¹^,* ,
秦安霖 ¹ ,
李小峰 ³

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1. 山西医科大学附属汾阳医院, 山西省汾阳医院风湿免疫科, 山西汾阳 032200
2. 临汾市妇幼保健院儿童医院, 山西临汾 041000
3. 山西医科大学第二医院风湿免疫科, 太原 030001

收稿日期: 2024-05-16

网络出版日期: 2026-03-12

基金资助

山西省吕梁市重点研发计划(社会发展)项目(2022SHFZ19)

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Small intestinal bacterial overgrowth and inflammatory factor expression levels in patients with asymptomatic hyperuricemia

Qianying WEN ¹^,² ,
Liqing ZHANG ^,¹^,* ,
Anlin QIN ¹ ,
Xiaofeng LI ³

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1. Department of Rheumatology and Immunology, Shanxi Fenyanq Hospital, Fenyang 032200, Shanxi, China
2. Linfen Maternal and Child Health Hospital Children's Hospital, Linfen 041000, Shanxi, China
3. Department of Rheumatology and lmmunology, Second Hospital of Shanxi Medical University, Taiyuan 030001, China

ZHANG Liqing，e-mail, zhanglq828@sohu.com

Received date: 2024-05-16

Online published: 2026-03-12

Supported by

Lvliang Key Research and Development Plan (Social Development) Project in Shanxi Province(2022SHFZ19)

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摘要

目的: 分析无症状高尿酸血症(hyperuricemia, HUA)患者小肠细菌过度生长(small intestinal bacterial overgrowth, SIBO)发生情况及无症状HUA合并SIBO患者血清中C-反应蛋白(C-reactive protein, CRP)、白细胞介素(interleukin, IL)-1β、IL-6和肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)表达水平。方法: 选取山西省汾阳医院2023年6月至2024年6月的87例无症状HUA患者和40例健康对照者为研究对象, 收集基线资料和实验室指标。采用乳果糖甲烷-氢呼气试验(lactulose methane-hydrogen breath test, LHBT)检测SIBO的发生情况, 并根据LHBT的检测结果将无症状HUA患者分为SIBO阳性组及SIBO阴性组, 分析无症状HUA患者SIBO阳性率, 比较无症状HUA患者与健康对照者各个时间点(0、30、60和90 min)H₂和CH₄浓度及CRP、IL-1β、IL-6、TNF-α水平, 以及SIBO阳性组和SIBO阴性组之间的CRP、IL-1β、IL-6、TNF-α水平。采用多因素Logistic回归分析无症状HUA患者发生SIBO的影响因素, 采用Spearman秩相关分析无症状HUA患者CRP、IL-1β、IL-6、TNF-α水平与SIBO的相关性。结果: 无症状HUA患者SIBO阳性率高于健康对照者, 差异有统计学意义(58.62% vs. 20.00%, χ²=16.431, P＜0.001)。无症状HUA患者与健康对照者呼出H₂浓度在各时间点差异均有统计学意义(P＜0.05), 但呼出CH₄浓度在各时间点差异均无统计学意义(P＞0.05)。无症状HUA患者CRP、IL-1β、IL-6、TNF-α水平高于健康对照者, 差异有统计学意义(P＜0.05)。无症状HUA患者SIBO阳性组血清CRP、IL-1β、IL-6水平均明显高于SIBO阴性组(P < 0.05), 但TNF-α水平在两组间差异无统计学意义(P＞0.05)。多因素Logistic回归分析分析表明, IL-1β升高(OR=1.332, 95%CI: 1.005~1.764, P=0.046)、IL-6升高(OR=1.586, 95%CI: 1.216~2.069, P=0.001)是无症状HUA患者发生SIBO的独立危险因素。无症状HUA合并SIBO患者中, LHBT集值与血清IL-1β成正相关(r=0.594, P＜0.001)。结论: 无症状HUA患者较健康人群更容易发生SIBO, 且SIBO的发生与炎症因子水平密切相关, 应重视无症状HUA患者SIBO的检测和干预。

关键词： 高尿酸血症; 无症状疾病; 小肠细菌过度生长; 炎症细胞因子; 胃肠道微生物组

本文引用格式

温倩颖 , 张丽卿 , 秦安霖 , 李小峰 . 无症状高尿酸血症患者小肠细菌过度生长及炎症细胞因子表达水平[J]. 北京大学学报（医学版）, 2026 , 58(2) : 313 -318 . DOI: 10.19723/j.issn.1671-167X.2026.02.014

Abstract

Objective: To analyze the incidence of small intestinal bacterial overgrowth (SIBO) in patients with asymptomatic hyperuricemia (HUA) and the serum levels of C-reactive protein (CRP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in patients with asymptomatic HUA and SIBO. Methods: A total of 87 asymptomatic HUA patients and 40 healthy controls from Shanxi Fenyang Hospital from June 2023 to June 2024 were selected as the study subjects, and the baseline data, laboratory indicators were collected. Lactulose methane-hydrogen breath test (LHBT) was used to detect the occurrence of SIBO, and the asymptomatic HUA patients was divided into SIBO-positive group and SIBO-negative group according to the test results of LHBT. The positive rate of SIBO in the asymptomatic HUA patients was analyzed, and the concentrations of H₂ and CH₄, the levels of CRP, IL-1β, IL-6 and TNF-α at each time point between the asymptomatic HUA patients and the healthy controls were compared, and the levels of CRP, IL-1β, IL-6 and TNF-α were compared between the SIBO-positive group and the SIBO-negative group. Multivariate Logistic regression analysis was performed to analyze the influencing factors of SIBO in asymptomatic HUA. Spearman rank correlation analysis was used to analyze the correlation between CRP, IL-1β, IL-6 and TNF-α levels and SIBO in asymptomatic HUA patients. Results: The positive rate of SIBO in the asymptomatic HUA patients was 58.62%, which was higher than that in the healthy controls (20.00%), and the difference was statistically significant (χ²=16.431, P < 0.001). There were significant differences in exhaled H₂ concentration between the asymptomatic HUA patients and the healthy controls at 0, 30, 60 and 90 min (P < 0.05), and there was no significant difference in exhaled CH₄ concentration at each time point (P>0.05). The levels of CRP, IL-1β, IL-6 and TNF-α in the asymptomatic HUA patients were significantly higher than those in the healthy controls (P < 0.05). The serum levels of CRP, IL-1β and IL-6 in the SIBO-positive group were significantly higher than those in the SIBO-negative group (P < 0.05), while the levels of TNF-α were not significantly different between the two groups (P>0.05). Multivariate Logistic regression ana-lysis of the influencing factors of SIBO in the asymptomatic HUA showed that increased IL-1β (OR=1.332, 95%CI: 1.005-1.764, P=0.046) and increased IL-6 (OR=1.586, 95%CI: 1.216-2.069, P=0.001) were independent risk factors for SIBO in the HUA patients. In asymptomatic HUA patients with SIBO, the LHBT set value was positively correlated with serum IL-1β (r=0.594, P < 0.001). Conclusion: Asymptomatic HUA patients are more likely to develop SIBO than healthy people, and SIBO in asymptomatic HUA patients is closely related to the level of inflammatory factors, so attention should be paid to the detection and intervention of SIBO in asymptomatic HUA patients.

Key words： Hyperuricemia; Asymptomatic diseases; Small intestinal bacterial overgrowth; Inflammatory cytokines; Gastrointestinal microbiome

无症状高尿酸血症(hyperuricemia，HUA)是指在正常嘌呤饮食条件下，血尿酸水平高于正常范围(>420 mmol/L)，但未出现痛风、关节炎等临床症状^[1]。据统计，我国HUA的患病率约为14%，且呈现出年轻化趋势^[2]。HUA的发生与肠道微生态的改变密切相关。小肠细菌过度生长(small intestinal bacterial overgrowth，SIBO)是肠道菌群失调的一种表现，其特征是细菌由远端结肠移位至小肠，导致小肠屏障功能受损，继而诱发全身性炎症反应^[3]。炎症反应是HUA进展中的关键病理机制，HUA不仅可导致炎症因子水平的升高，且炎症因子反过来会加剧HUA的发展。已有研究表明，肠道菌群失调与HUA之间存在潜在联系，但无症状HUA患者的肠道微生态变化及其与炎症因子水平的关系仍不清楚^[4]。本研究探讨无症状HUA患者中SIBO的发生情况并分析SIBO与炎症因子水平的关联，旨在为临床提供新的干预思路。

1 资料与方法

1.1 研究对象

以山西省汾阳医院2023年6月至2024年6月的体检人群为研究对象，根据纳入和排除标准筛选87例无症状HUA患者，同时选择40名年龄、性别、体重指数(body mass index，BMI)与之相匹配的血尿酸≤420 mmol/L者作为健康对照。

1.2 纳入和排除标准

无症状HUA患者纳入标准：(1)符合《中国高尿酸血症与痛风诊疗指南(2019)》诊断标准^[4]；(2)无临床症状，未进行降尿酸治疗；(3)年龄18~60岁。排除标准：(1)已知高血压、糖尿病、冠心病、脑卒中及正在治疗的血脂异常患者；(2)既往有痛风发作史；(3)近3个月内服用影响尿酸水平的药物；(4)近4周内因消化道病变而引发胃肠机能失调症状；(5)近2周内服用对肠道菌群存在影响的药物，如抗生素、活菌制剂、泻药等。本研究通过山西省汾阳医院医学伦理委员会审查(批准号：2022045)，所有受试者均签署知情同意书。

1.3 数据收集

收集患者和健康人群的一般资料，包括年龄、性别和BMI。采集空腹静脉血，采用日本SYSMEX全自动生化分析仪测定血常规及血生化指标，并计算中性粒细胞与淋巴细胞比值。采用双抗体夹心酶联免疫吸附法(enzyme-linked immunosorbent assay，ELISA)测定C-反应蛋白(C-reactive protein，CRP)、白细胞介素(interleukin，IL)-1β、IL-6和肿瘤坏死因子-α(tumor necrosis factor-α，TNF-α)水平。

1.4 乳果糖甲烷-氢呼气试验

采用QuinTron Breath Tracker^TM Digital MicroLyzer SC呼气仪(美国Quin Tron公司)进行乳果糖甲烷-氢呼气试验(lactulose methane-hydrogen breath test，LHBT)。先在空腹状态下进行第1次采样，然后快速口服乳果糖10 g，再进行3次取样，每次间隔30 min(共完成4次取样，取样时间点分别为0、30、60、90 min)。参照《北美共识：小肠细菌过度生长诊断与管理》^[5]，90 min内呼出气体中氢气(H₂)浓度较基线升高≥20 ppm(1 ppm=10^-6)或90 min内某一时间点的呼出气体中甲烷(CH₄)浓度≥10 ppm，即可诊断为SIBO。根据LHBT检测结果，将无症状高尿酸血症患者进一步分为SIBO阳性组与SIBO阴性组。将90 min内的4次H₂浓度之和作为LHBT集值，间接反映小肠内细菌生长情况^[6]。

1.5 统计学方法

应用SPSS 26.0软件进行统计学分析。数据正态性采用Shapiro-Wilk检验，方差齐性采用Levene检验进行评估。满足正态分布且方差齐性的计量资料用${\bar x}$±s表示，组间比较采用独立样本t检验；不符合正态分布的计量资料用M(P₂₅，P₇₅)表示，组间比较采用Mann-Whitney U检验；计数资料用n(%)表示，组间比较采用卡方检验。为探讨无症状HUA患者发生SIBO的独立影响因素，将单因素分析中具有统计学意义的变量纳入多因素Logistic回归模型进行分析。采用Spearman秩相关分析评估无症状HUA合并SIBO患者炎症因子(CRP、IL-1β、IL-6、TNF-α)水平与LHBT集值之间的相关性。P＜0.05为差异具有统计学意义。

2 结果

2.1 无症状HUA患者与健康对照者基本信息及SIBO阳性率比较

无症状HUA患者与健康对照者年龄、性别及BMI差异无统计学意义(P>0.05)。无症状HUA患者中有51例(58.62%)SIBO阳性，健康对照者中有8人(20.00%)SIBO阳性，差异有统计学意义(P < 0.001，表 1)。

表1 无症状HUA患者与健康对照者的基本信息及SIBO阳性率比较

Table 1 Comparison of basic information and SIBO positive rate between asymptomatic HUA patients and healthy controls

Items	Asymptomatic HUA (n=87)	Healthy control (n=40)	Statistic	P value
Gender, n(%)			χ²=0.543	0.461
Male	62 (71.26)	31 (77.50)
Female	25 (28.74)	9 (22.50)
Age/years, ${\bar x}$±s	40.11±7.65	38.13±8.17	t=-1.333	0.185
BMI/(kg/m²), ${\bar x}$±s	26.33±2.33	24.83±2.61	t=-1.394	0.167
SIBO, n(%)			χ²=16.431	＜0.001
Positive	51 (58.62)	8 (20.00)
Negative	36 (41.38)	32 (80.00)

HUA, hyperuricemia; SIBO, small intestinal bacterial overgrowth; BMI, body mass index.

2.2 无症状HUA患者与健康对照者呼出气体中H₂及CH₄浓度比较

无症状HUA患者与健康对照者呼出气体中H₂浓度在各时间点(0、30、60、90 min)差异均有统计学意义(P < 0.05)，但CH₄浓度在各时间点差异均无统计学意义(P>0.05，表 2)。

表2 无症状HUA患者与健康对照者LHBT结果

Table 2 LHBT results for asymptomatic HUA patients and healthy controls

Items	Asymptomatic HUA (n=87)	Healthy controls (n=40)	Z value	P value
H₂，M(P₂₅, P₇₅)
Baseline	7.00 (4.00, 12.00)	5.00 (4.00, 9.00)	-2.100	0.036
30 min	11.00 (6.00, 15.00)	6.00 (4.25, 11.50)	-2.676	0.007
60 min	10.00 (5.00, 16.00)	5.00 (4.00, 11.25)	-2.910	0.004
90 min	12.00 (8.00, 24.00)	8.00 (5.00, 14.00)	-3.049	0.002
CH₄，M(P₂₅, P₇₅)
Baseline	6.00 (4.00, 9.00)	6.50 (4.00, 8.00)	-0.329	0.742
30 min	7.00 (4.00, 9.00)	7.00 (5.25, 8.00)	-0.089	0.929
60 min	6.00 (4.00, 10.00)	6.00 (5.00, 8.00)	-0.723	0.470
90 min	7.00 (5.00, 12.00)	7.00 (4.00, 8.00)	-1.714	0.086

HUA, hyperuricemia; LHBT, lactulose methane-hydrogen breath test.

2.3 无症状HUA患者与健康对照者炎症因子比较

无症状HUA患者血清CRP、IL-1β、IL-6和TNF-α水平均明显高于健康对照者，差异有统计学意义(P < 0.05，表 3)。

表3 无症状HUA患者与健康对照者的炎症因子比较

Table 3 Comparison of inflammatory factors between asymptomatic HUA patients and healthy controls

Items	Asymptomatic HUA (n=87)	Healthy controls (n=40)	Z value	P value
CRP/(mg/L)，M(P₂₅, P₇₅)	20.00 (10.00, 33.00)	5.00 (3.00, 11.00)	-7.596	＜0.001
IL-1β/(ng/L)，M(P₂₅, P₇₅)	4.67 (3.38, 6.62)	2.03 (1.45, 2.77)	-5.955	＜0.001
IL-6/(ng/L)，M(P₂₅, P₇₅)	3.42 (2.01, 6.07)	2.46 (1.22, 3.65)	-2.852	0.004
TNF-α/(ng/L)，M(P₂₅, P₇₅)	1.21 (0.81, 1.77)	0.97 (0.61, 1.23)	-2.943	0.003

HUA, hyperuricemia; CRP, C-reactive protein; IL-1β, interleukin-1β; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α.

2.4 无症状HUA患者SIBO阳性组与SIBO阴性组临床指标和炎症因子比较

无症状HUA患者SIBO阳性组和阴性组性别、年龄、BMI及各项血常规、血生化指标差异均无统计学意义(P>0.05)，但在炎症因子方面，SIBO阳性组患者血清CRP、IL-1β、IL-6水平明显高于SIBO阴性组，差异均有统计学意义(P < 0.05)，而TNF-α水平在两组间差异无统计学意义(P＞0.05，表 4)。

表4 无症状HUA患者SIBO阳性组与SIBO阴性组的临床和实验室指标比较

Table 4 Comparison of clinical and laboratory indicators between the SIBO positive and SIBO negative groups of asymptomatic HUA patients

Items	SIBO positive group (n=51)	SIBO negative group (n=36)	Statistics	P value
Gender			χ²=0.634	0.426
Male	38 (74.51)	24 (66.67)
Female	13 (37.25)	12 (33.33)
Age/years	40.98±5.35	38.89±10.01	t=1.144	0.258
BMI/(kg/m²)	26.14±2.20	26.60±2.50	t=-0.917	0.362
Laboratory indicators
WBC/(×10⁹/L)	7.12±1.94	7.37±2.43	t=-0.512	0.610
HGB/(g/L)	160.71±13.54	158.42±11.65	t=0.822	0.413
PLT/(×10⁹/L)	239.00±40.74	233.83±40.74	t=0.550	0.584
NLR	2.36 (1.56, 3.40)	2.11 (1.51, 2.36)	Z=1.896	0.058
ALT/(U/L)	28.45±9.05	25.66±6.50	Z=1.674	0.098
AST/(U/L)	30.35±7.81	30.28±13.59	t=0.033	0.976
BUN/(mmol/L)	5.73±1.10	5.51±1.33	t=0.820	0.415
GGT/(mmol/L)	35.63±15.19	38.22±16.28	t=-0.762	0.448
Scr/(μmol/L)	81.45±17.31	78.60±19.24	t=0.321	0.749
UA/(μmol/L)	507.94±44.72	504.25±51.96	t=0.354	0.724
TC/(mmol/L)	4.74±0.88	4.64±0.71	t=0.571	0.570
TG/(mmol/L)	3.09±0.82	4.64±0.71	t=0.739	0.462
HDL-C/(mmol/L)	1.00±0.32	1.08±0.21	t=-1.601	0.113
LDL-C/(mmol/L)	2.83±0.68	2.73±0.63	t=0.631	0.535
CRP/(mg/L)	24.00 (13.00, 36.00)	16.50 (7.25, 29.75)	Z=2.069	0.039
IL-1β/(ng/L)	5.23 (3.67, 7.21)	4.04 (3.04, 5.64)	Z=2.366	0.018
IL-6/(ng/L)	4.54 (3.18, 8.02)	2.13 (0.97, 3.53)	Z=4.456	＜0.001
TNF-α/(ng/L)	1.25 (0.88, 1.86)	1.10 (0.77, 1.74)	Z=1.418	0.156

Data are expressed as n(%), ${\bar x}$±s or M (P₂₅, P₇₅). HUA, hyperuricemia; SIBO, small intestinal bacterial overgrowth; BMI, body mass index; WBC, white blood cell; HGB, hemoglobin; PLT, platelet; NLR, absolute neutrophil count (ANC)/ absolute lymphocyte count (ALC); ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; GGT, gamma-glutamyl transferase; Scr, serum creatinine; UA, uric acid; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; CRP, C-reactive protein; IL-1β, interleukin-1β; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α.

2.5 无症状HUA患者发生SIBO的影响因素分析

以无症状HUA患者是否发生SIBO为因变量(是=1，否=0)，以组间比较差异有统计学意义的因素为自变量进行多因素Logistic回归分析，结果显示，IL-1β升高(OR=1.332，95%CI：1.005~1.764，P=0.046)、IL-6升高(OR=1.586，95%CI：1.216~2.069，P=0.001)是无症状HUA患者发生SIBO的独立危险因素(表 5)。

表5 多因素Logistic回归分析无症状HUA患者发生SIBO的影响因素

Table 5 Multivariate Logistic regression analysis of the influencing factors of SIBO in asymptomatic HUA patients

Items	B	SE	Wald χ²	P	OR (95%CI)
CRP	-0.017	0.020	0.730	0.393	0.983 (0.946-1.022)
IL-1β	0.286	0.144	3.983	0.046	1.332 (1.005-1.764)
IL-6	0.461	0.136	11.549	0.001	1.586 (1.216-2.069)

HUA, hyperuricemia; SIBO, small intestinal bacterial overgrowth; CRP, C-reactive protein; IL-1β, interleukin-1β; IL-6, interleukin-6.

2.6 无症状HUA合并SIBO患者血清炎症因子水平与LHBT集值的相关性分析

无症状HUA合并SIBO患者中，LHBT集值与血清IL-1β水平呈中等强度正相关，且该相关性具有统计学意义(r=0.594，P＜0.001, 图 1)，而LHBT集值与CRP、IL-6、TNF-α水平虽呈正相关，但相关性无统计学意义(r=0.271，P=0.055；r=0.167，P= 0.241；r=0.048，P=0.737)。

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图1 无症状HUA合并SIBO患者LHBT集值与血清IL-1β水平的相关性散点图

Figure 1 Scatter plot of the correlation between LHBT values and serum IL-1β levels in asymptomatic HUA patients with SIBO

HUA, hyperuricemia; SIBO, small intestinal bacterial overgrowth; LHBT, lactulose methane-hydrogen breath test; IL-1β, interleukin-1β.

3 讨论

无症状HUA是HUA的早期阶段，指血尿酸水平达到HUA标准，但无急性关节炎等临床症状^[4]。作为肠道菌群失调的一种类型，SIBO由细菌移位引发，细菌由远端结肠转至小肠，造成小肠细菌过度繁殖增长，继而出现小肠吸收不良、腹泻、腹胀等症状^[6]。在过去的认知里，SIBO被视为极少见的一种症状，只发生于近端消化道结构不良或严重的消化道动力不足的患者中；随着研究的不断深入，发现除了炎症性肠病、肠易激综合征等消化系统疾病，SIBO还可能与多种自身免疫病相关^[7-9]。目前，SIBO与炎症因子的相关性研究已有了部分成果——SIBO可引起脂多糖表达升高，并且会诱导IL-1β、IL-6、IL-8和TNF-α等炎症因子的产生，导致机体慢性炎症状态^[10]。然而，无症状HUA合并SIBO患者的炎性因子表达水平变化尚不明确。因此，本研究分析了无症状HUA与SIBO的相关性及其炎症介质水平的变化。

无症状HUA患者存在肠道菌群的改变。国外研究发现无症状HUA患者展现出较高的厚壁菌门/拟杆菌门(Firmicutes/Bacteroidetes，F/B)比值和较低的普氏菌属/拟杆菌属(Prevotella/Bacteroides，P/B)比值，这种F/B比值的变动被看作是肠道微生态失衡的标志^[11-12]。SIBO属于肠道微生态失衡的一种，目前，有效诊断SIBO的方法有多种，其中LHBT是近年兴起的检测技术。2017年的《北美共识：小肠细菌过度生长诊断与管理》^[5]推荐将LHBT作为临床实际工作中的首选检测方法，因此，本研究采用LHBT评估SIBO。本研究结果发现，无症状HUA患者SIBO阳性率较健康对照者高，表明无症状HUA患者较正常人群更易患SIBO。此外，无症状HUA患者各个时间点呼出气体中H₂浓度均高于健康对照组，提示无症状HUA可能与SIBO存在联系。有研究发现变形菌属(Proteus)和普氏菌属均与肠道产氢量正相关^[13-15]，通过16s rRNA分析也发现SIBO与弯曲杆菌属(Campylobacter)的显著增加有关^[16]，表明无症状HUA合并SIBO患者可能存在以上菌群失调，但该结论尚待进一步验证。

炎症反应是导致HUA损伤的关键病理因素。HUA可致炎症因子水平升高，高水平的炎症因子又可诱发炎症反应使HUA程度加重。白细胞免疫球蛋白样受体2/Toll样受体4-核因子κB(leukocyte immunoglobulin-like receptor 2 / Toll-like receptor 4-nuclear factor kappa B，LR2/TLR4-NF-κB)信号通路是尿酸启动炎症反应的经典通路^[17]。NF-κB被上游蛋白激活后，会导致多种炎症因子的级联放大反应，引起炎症因子的表达水平升高，从而导致不可逆转的组织损伤和功能丧失^[18]。有研究表明HUA患者IL-1β和IL-6的水平显著增高，并且当健康受试者的细胞用尿酸预处理时，促炎细胞因子的生成亦显著增加^[19]。CRP、IL-1β、IL-6、TNF-α作为典型的炎性因子，在机体多种生理过程中起着重要的调控作用，是炎症反应的重要指标。本研究中无症状HUA组CRP、IL-1β、IL-6、TNF-α表达水平明显高于健康对照组，证实了炎症细胞因子水平与无症状HUA的发生、发展过程的相关性。

研究表明，SIBO能引起肠道菌群新陈代谢发生变化以及小肠屏障功能受损，细菌的代谢物可以穿过肠道上皮屏障，与其他免疫细胞(如巨噬细胞、树突细胞、肥大细胞等)发生直接接触，激活其炎症介质的分泌，引起免疫应答及炎性反应^[20]。同时，炎症介质对肠黏膜屏障功能的破坏会导致其渗透选择性降低，造成细菌移位，使菌群紊乱进一步恶化^[21]。在无症状HUA患者中，SIBO的存在与更明显的全身炎症活动有关，特别是血清IL-1β、IL-6水平的升高是SIBO存在的独立因素。此外，无症状HUA合并SIBO患者的呼出气体中H₂浓度峰值与IL-1β水平之间存在很强的相关性。尽管IL-1β在HUA的病理生理学中具有明确的作用^[22]，但关于SIBO患者IL-1β水平变化的研究较少见。有研究发现，肠易激综合征患者在SIBO阳性时具有较高的小肠黏膜IL-1β水平^[23]。本研究也发现了SIBO与IL-1β水平升高之间的联系，但本研究仍存在如下的局限性：(1)属于单中心的横断面研究，无法验证SIBO与炎症介质水平的因果关系；(2)样本量较少，可能有选择偏倚。今后将进行前瞻性队列研究以进一步明确无症状HUA与SIBO及炎性因子水平的关系。

综上所述，无症状HUA与SIBO及炎症因子水平密切相关。因此，门诊体检时如发现无症状HUA患者，可建议其完善LHBT，以评估是否存在SIBO，从而给予相应治疗，恢复肠道微生态的平衡，这可能会减少炎症因子的产生，延缓HUA进程。

利益冲突 所有作者均声明不存在利益冲突。

作者贡献声明 温倩颖：论文撰写、数据收集、统计学分析；张丽卿：研究设计指导，论文审校；秦安霖：数据收集；李小峰：实验支持。所有作者均参与论文修改，并对最终文稿进行审读和确认。

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