基于肠道菌群代谢产物探索低FODMAPs饮食对腹泻型肠易激综合征的疗效及机制研究

Study of efficacy and mechanism of low FODMAPs diet on diarrhea-type irritable bowel syndrome based on a gut microbiota-dependent metabolite

背景肠易激综合征(irritable bowel syndrome,IBS)的发生与肠道菌群紊乱引起代谢产物异常改变相关.低可发酵的寡糖、双糖、单糖、多元醇(fermentable oligosaccharides,disaccharides,monosaccharides and polyols,FODMAPs)饮食在IBS治疗上是否通过影响肠道菌群代谢产物苯丙氨酸(phenylalanine,PHE)的产生进而起到治疗作用的研究具有重要意义.目的观察低FODMAPs饮食在腹泻型IBS(diarrhea-type irritable bowel syndrome,IBS-D)治疗上的疗效及其通过肠道菌群代谢产物PHE调控胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)的分子机制.方法选择30例符合罗马Ⅳ标准的IBS-D患者入组,予低FODMAPs饮食,疗程4周.征集30名健康志愿者作基线检测对照.观察健康志愿者及IBS组患者治疗前后的临床症状评分,检测血清PHE,GLP-1,TNF-α,IFN-γ.采用NCI-H716细胞,加入不同浓度PHE,观察PHE对GLP-1的影响.结果经低FODMAPs饮食干预后,IBS患者临床症状评分较治疗前明显降低(P<0.0001&P<0.001);IBS组血清PHE和GLP-1浓度较前上升(P<0.05),TNF-α和IFN-γ浓度较前下降(P<0.0001&P<0.001).试验过程中无一例出现不良反应.体外实验发现,1 mmol/L PHE可以显著促进GLP-1分泌.结论低FODMAPs饮食能改善IBS-D患者临床症状,其作用机制可能与饮食因素影响肠道菌群代谢产物PHE调控GLP-1,抑制促炎细胞因子分泌相关.

BACKGROUND The changes in gut microbiota-dependent metabolites can cause irritable bowel syndrome(IBS).It is important to investigate whether a diet low in fermentable oligosaccharides,disaccharides,monosaccharides,and polyols(FODMAPs)plays a therapeutic role in IBS treatment by affecting the production of phenylalanine(PHE),a gut microbiota-dependent metabolite.AIM To investigate the efficacy of a low FODMAPs diet in diarrhea-type irritable bowel syndrome(IBS-D)and its molecular mechanism for regulating GLP-1 secretion by affecting PHE,a gut microbiota-dependent metabolite.METHODS Thirty patients who met the Rome IV diagnostic criteria for IBS-D were enrolled and treated with a low FODMAPs diet for 4 wk.Thirty healthy volunteers served as baseline controls.The changes of clinical symptom scores,and serum PHE,GLP-1,and TNF-α,as well as IFN-γbefore and after treatment were recorded.In in vitro experiment,different doses of PHE were added into NCI-H716 cells to observe the regulatory effect of PHE on GLP-1.RESULTS The clinical symptom scores after treatment in the IBS group were significantly lower than those before treatment(P<0.0001&P<0.001).After treatment,the levels of PHE and GLP-1 increased(P<0.05),but those of TNF-αand IFN-γdecreased significantly(P<0.0001&P<0.001).No adverse reactions occurred in the IBS group.In in vitro experiment,GLP-1 expression levels were found to rise with increasing PHE concentrations,and 1 mmol/L PHE could significantly increase GLP-1 secretion.CONCLUSION Low FODMAPs diet improves the symptoms in IBS-D patients via mechanisms that may be related to the regulation of GLP-1 by affecting PHE and thereby inhibiting the secretion of pro-inflammatory cytokines.