关于小肠细菌过度生长阳性标准之我见

1、关于90分钟时H2-基线>20PPM,或CH4-基线>12PPM.

《北美共识》的建议是：A rise in hydrogen of ≥20 p.p.m. by 90 min during glucose or lactulose BT for SIBO was considered positive. Methane levels ≥10 p.p.m. was considered methane positive.

Reference 1: Rezaie A, Buresi M, Lembo A, et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. A m J Gastroenterol 2017; 112:775–784.

Reference 2：北美共识建议，甲烷水平≥10ppm的存在可诊断产甲烷过度生长。然而，一些专家建议甲烷含量上升10 ppm，这需要确认。

呼气样本应测量氢和甲烷。如前所述，建议在90–120分钟内将氢浓度从基线水平增加≥20ppm作为SIBO的诊断。

Pimentel M, Saad R, Long M, et al. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth, The Am J Gastroenter: Feb 2020 - Vol 115 - Issue 2 - p 165-178.

2、关于30分钟时，H2>20PPM, 或CH4>12PPM

这个需要考虑空腹值判断。

3、关于30分钟时，H2-基线>20PPM,或CH4-基线>12PPM    

我没有看到以此为标准的研究报告。但是，我认为以这个为标准有一定的合理性。考虑到喝进底物溶液后，有可能在30分钟到达小肠近端。《北美共识》的标准是H2>20PPM, 或CH4>10PPM.

4、关于CH4基线值≥5PPM

参见：

Reference: Gottlieb K, Le C, Wacher V, et al. Gottlieb K, Le C, Wacher V, et al. Selection of a cut-off for high- and low-methane producers using a spot-methane breath test: results from a large north American dataset of hydrogen, methane and carbon dioxide measurements in breath. Gastroenterol Rep (Oxf). 2017 Aug; 5(3): 193–199.

5、H2+CH4-二者基线和>15PPM  厂家建议，

考虑到产甲烷菌会消耗氢气，如果用H2-基线≥20PPM的标准，会出现假阴性。这种考虑有合理性，但是就具体数值来源缺少研究证明。考虑每产生一个甲烷分子需要消耗4个氢分子。用H2+CH4-二者基线和>15PPM作为阳性标准是否合理需要实验验证。在没有更好的标准之前，我们只能用这个数值作为一个参考。

6、关于基线时, H₂基线值>20PPM, 或CH₄基线值>10PPM

对这个标准存在几种不同的争议：

争议一：认为这是消化不良

SIBO should be excluded prior to BT for carbohydrate malabsorption to avoid false positives. A rise in hydrogen of ≥20 p.p.m. from baseline during BT was considered positive for maldigestion.

Reference: Rezaie A, Buresi M, Lembo A, et al. Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus. A m J Gastroenterol 2017; 112:775–784.

争议二：认为可以诊断为小肠细菌过度生长阳性

Small-intestinal bacterial overgrowth was determined by glucose-hydrogen breath test (GHBT). A basal breath-hydrogen >20 ppm or a rise by > or = 12 ppm above baseline following glucose administration was taken as positive test. Prevalence of SIBO in cirrhotics was compared with healthy controls and correlated with severity of cirrhosis.

Reference: Pande C, Kumar A, Sarin SK. Small-intestinal bacterial overgrowth in cirrhosis is related to the severity of liver disease. Aliment Pharmacol Ther. 2009;29;1273-1281.

In another study by Riordan et al22 from Australia, median fasting breath hydrogen among 45 controls was 5 ppm (range, 1-19). This is in accordance with the results in our control population. In that study, the upper 95% confidence limit (mean + 2 standard deviation) of square root of fasting breath hydrogen value was 4 ppm, corresponding to a measured value of fasting breath hydrogen of 16 ppm. Hence, the authors considered > 16 ppm as abnormal and considered it to be diagnostic of small intestinal bacterial overgrowth (SIBO) with a sensitivity and specificity of 22% and 75%, respectively considering the result of quantitative bacterial culture of distal duodenal aspirate as the gold standard.

Reference: Kumar S, Misra A, and Ghoshal UC. Patients with irritable bowel syndrome exhale more hydrogen than healthy subjects in fasting state. J Neurogastroenterol Motil. 2010;16:299–305.

Riordan SM, Mciver CJ, Bolin TD, and Duncombe VM. Fasting breath hydrogen concentrations in gastric and small intestinal bacterial overgrowth. Scand J Gastroenterol. 1995;30:252–257.

争论三：认为不可以诊断为小肠细菌过度生长阳性

This is in discordance with our previous studies that showed 8.5% to 13% IBS had SIBO compared with 2% HC using glucose hydrogen breath test; these data, therefore, further substantiate that fasting breath hydrogen alone should not be used as a criterion for diagnosis of SIBO as reported by some authors previously. Poor performance of fasting breath hydrogen in diagnosis of SIBO has been shown by Riordan et al too.

Reference: Kumar S, Misra A, and Ghoshal UC. Patients with irritable bowel syndrome exhale more hydrogen than healthy subjects in fasting state. J Neurogastroenterol Motil. 2010;16:299–305.

小结：我的观点

氢和甲烷呼气试验是一种无创检查小肠细菌过度生长的方法，关于用呼气试验诊断小肠细菌过度生长存在多种因素的影响，包括年龄、胃肠动力、身体状态、基础病、饮食、呼气试验取样时间、药物、患者检查前的准备、小肠细菌发酵等。

鉴于还缺少中国人，甚至亚洲人的诊断标准，我们目前只能参考《罗马共识》、《北美共识》、《美国指南》和《欧洲指南》。

《美国胃肠学会临床指南：小肠细菌过度生长》提到的观点值得作为诊断小肠细菌过度生长的考虑。

认识到呼气实验的局限性是很重要的，因此，在临床实验的登记过程中，同时出现症状也是至关重要的。SIBO最突出的症状是腹胀。因此，对于临床实验的登记和主要登记症状，应将此症状视为强制性的。然而，SIBO的其他特征也可以作为次要症状来检查，例如腹泻、腹痛、肠胃气胀、打嗝，甚至便秘（在甲烷的情况下）。虽然没有腹胀的阈值，但在没有经过验证的患者报告结果的情况下，SIBO的主要症状应该由患者在入组的至少50%天内经历。

Pimentel M, Saad R, Long M, et al. ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth, The Am J Gastroenter: Feb 2020 - Vol 115 - Issue 2 - p 165-178.

我个人的观点认为为了更好地诊断小肠细菌过度生长，需要：

1、检查结果与临床症状和病史结合

2、考虑肠道外症状和炎症反应的检查

3、尽可能缩短取样的间隔时间。

4、尽可能把临床症状作为考虑检查持续时间长短的因素。

3和4确实对中国临床检查是一个挑战。