肠易激综合征患者合并小肠细菌过度生长的临床特征及利福昔明治疗效果初探

Clinical features of irritable bowel syndrome with small intestinal bacterial overgrowth and a preliminary study of effectiveness of Rifaximin

目的应用氢气结合甲烷乳果糖呼气试验（LBT）研究腹泻型肠易激综合征（IBS-D）患者中小肠细菌过度生长（SIBO）的发生率和临床特征，并初步探讨利福昔明对IBS-D患者的疗效。方法纳入2015年3月至2016年1月就诊于北医三院消化科门诊符合罗马Ⅲ标准的IBS-D患者和年龄、性别相匹配的健康志愿者，应用LBT检测IBS-D患者中SIBO发生率并分析IBS-D合并SIBO（IBS-P组）和不合并SIBO（IBS-N组）患者的临床特征及LBT特点。应用利福昔明（0.4 g，2次/d）对IBS-D患者进行4周治疗，比较治疗前、后不同组患者临床症状和LBT变化。 结果（1）共纳入84例IBS-D患者和22名健康志愿者（对照组），IBS-D中SIBO发生率为41.67%（35/84），其中单纯氢气呼气试验阳性者27例（77.14%），单纯甲烷呼气试验阳性者5例（14.29%），二者均阳性者3例（8.57%）。（2）IBS-P组的体质量指数（BMI）低于IBS-N组[（21.61±0.57）比（23.44±0.54）kg/m2，P〈0.05]，最多排便次数少于IBS-N组[ （3.85±0.23）比（4.88±0.35）次/d，P〈0.05]。（3）IBS-P组、IBS-N组和对照组的口盲传输时间差异无统计学意义。IBS-P组小肠段和结肠段呼气中氢气丰度显著高于对照组和IBS-N组，小肠段和结肠段（160 min处）甲烷丰度高于IBS-N组（均P〈0.05）。（4）IBS-P组、IBS-N组和对照组的平均呼气氢气丰度和甲烷丰度无显著线性相关（均r〈0.35，P〉0.05）。（5）IBS-P组接受利福昔明治疗13例，治疗后患者腹痛、腹胀、粪便性状、排便次数和排便不满意度显著好转（均P〈0.05）；IBS-N组接受治疗8例，患者粪便性状、排便次数和排便不满意度较治疗前好转（均P〈0.05）。（6）IBS-P组患者利福昔明治疗后LBT转阴率为5/13，各时间点呼气中氢气丰度均下降，结肠段（120 min处）更为显著[（34.54±7.32）×10^－6比（52.23±9.40）×10^－6，P〈0.05]；各时间点呼气中甲烷丰度亦有下降，小肠段（80 min处）最为显著[（8.54±0.95）×10^－6比（11.31±0.94）×10^－6，P〈0.05]。结论符合罗马Ⅲ诊断标准的IBS-D患者中约41.67%存在SIBO，氢气结合甲烷LBT较单纯氢气LBT具有更好的检出率；合并SIBO会影响IBS-D患者的营养状况；利福昔明可以显著改善合并SIBO的IBS-D患者的整体临床症状，降低呼气中氢气与甲烷丰度，但对不合并SIBO的IBS-D患者仅对腹泻症状有改善；两组的肠道菌群构成可能存在差异。

ObjectiveTo investigate the prevalence and clinical features of small intestinal bacterial overgrowth （SIBO） in diarrhea-predominant irritable bowel syndrome （IBS-D） patients detected by hydrogen and methane in lactulose breath test （LBT）, and to study the effects of rifaximin in IBS-D patients.MethodsConsecutive patients with IBS-D who met Rome Ⅲ criteria, and gender- and age-matched healthy volunteers were enrolled from March 2015 to January 2016 in Peking University Third Hospital. All the ISB-D patients underwent LBT to detect the prevalence of SIBO. The clinical and LBT features of IBS with SIBO （IBS-P group） and without SIBO （IBS-N group） were analyzed. The effects of rifaximin therapy （0.4 g, twice per day for 4 weeks） in IBS-D patients were evaluated by comparing changes in clinical features and LBT results after treatment.Results（1） Eighty-four IBS-D patients and 22 healthy controls were enrolled. The prevalence of SIBO in IBS-D patients was 41.67% （35/84）, with 27 （77.14%） only hydrogen-positive, 5 （14.29%） methane-positive, and 3 （8.57%） both methane- and hydrogen-positive. （2） The body mass index （BMI） in the IBS-P group was lower than in the IBS-N group [（21.61±0.57） vs （23.44±0.54） kg/m2,P〈0.05], the maximum stool frequency was also less than in the IBS-N group [（3.85±0.23） vs （4.88±0.35） times/day, P〈0.05]. （3） No significant difference was found in oro-cecal transit time （OCTT） among IBS-P, IBS-N and healthy controls. The hydrogen concentration in small intestinal and colonic sections in breath of the IBS-P group was higher than that of both healthy controls and the IBS-N group, while methane concentration in small intestinal and colonic sections （160 min） was higher than that of the IBS-N group （all P〈0.05）. （4） There was no linear relationship between mean hydrogen and methane concentrations in LBT among the IBS-P, the IBS-N and healthy control groups （all r〈0.35, P〉0.05）. （5） Totally 13 IBS-P patients received rifaximin therapy, in whom the symptoms of abdomen pain, bloating, fecal consistency, stool frequency, and stool satisfactory were significantly improved after treatment （all P〈0.05）; 8 IBS-N patients received rifaximin therapy, in whom fecal consistency, stool frequency, and satisfactory were significantly improved （all P〈0.05）. （6） And 5/13 of the IBS-P patients receiving rifaximin presented negative LBT results after rifaximin therapy, with lower hydrogen concentration at all the time points, especially in colonic section （120 min） [（34.54±7.32） ×10^-6 vs （52.23±9.40） ×10^-6,P〈0.05] and lower methane concentration especially in small intestinal section （80 min） [（8.54±0.95） ×10^-6 vs （11.31±0.94） ×10^-6,P〈0.05].ConclusionsAbout 41.67% of the IBS-D patients meeting Rome Ⅲ criteria have SIBO, which can be better screened by combining hydrogen and methane in LBT compared with only hydrogen in LBT. SIBO can affect nutritional status in IBS-D patients. Rifaximin can improve the systematic symptoms of IBS-D patients with SIBO, also reduce hydrogen and methane concentration in breath, while only improving diarrhea in IBS-D patients without SIBO. Some differences in gut microbiota may exist between IBS-D with and without SIBO.