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

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

摘要/Abstract

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

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

中图分类号:

R589

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.

Qianying WEN, Liqing ZHANG, Anlin QIN, Xiaofeng LI. Small intestinal bacterial overgrowth and inflammatory factor expression levels in patients with asymptomatic hyperuricemia[J]. Journal of Peking University (Health Sciences), 2026, 58(2): 313-318.

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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)

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

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

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

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)