CGH：胆汁酸合成与肠易激综合征腹泻有关

　　日前，来自美国明尼苏达的Michael Camilleri医师在《临床胃肠病学与肝病学》（Clin Gastroenterol Hepatol）发表论文，指出调节胆汁酸合成的基因变异与肠易激综合征（IBS）患者的结肠传输有关。

　　研究者研究了胆汁酸合成和分泌的特点以及不同类型IBS患者的遗传特点。

　　该研究团队在26名健康志愿者、26名IBS和便秘患者、26名IBS和腹泻患者中测定了血清7a-羟基-4-胆甾烯-3-酮和成纤维细胞生长因子（FGF）19水平。还测定了粪便样本的胆汁酸浓度、重量和高脂肪饮食时的脂肪含量，并采用Spearman相关性评价各因素之间的关系。他们采用协方差分析分析了各组全部成员Klotho—β（KLB）的1处多态性和成纤维细胞生长因子受体-4（FGFR4）的3处多态性。他们发现粪便中的胆汁酸浓度与组别有关，腹泻型IBS患者高于便秘型IBS患者。还发现腹泻型IBS患者中血清C4水平高于便秘型IBS患者与健康志愿者。

　　研究者观察到，与健康志愿者相比，38%的腹泻型IBS患者血清C4水平升高。他们发现血清C4水平与粪便胆汁酸浓度、血清FGF19水平及粪便重量相关。粪便胆汁酸浓度与体重和脂肪水平相关。体重指数与血清C4水平和粪便胆汁酸浓度相关，在腹泻性IBS患者中高于其它组。他们还发现FGFR4 rs 1966265与粪便胆汁酸水平相关。

　　Camilleri医师的团队评论说：“腹泻型IBS患者体重指数更高，合成和分泌的胆汁酸水平较便秘型IBS或健康志愿者更高；血清C4 水平可用于确定胆汁酸吸收不良的腹泻型IBS患者，还需要研究确定是否有某些患者具有这一疾病的遗传易感性”。

与腹泻相关的拓展阅读：

• PLOS ONE：含抗菌溶菌酶山羊奶可加快腹泻康复速度
• FDA批准首个用于HIV/AIDS患者抗腹泻药
• 联合国儿基会：洗手是预防腹泻病最简宜方法
• 临床实践——慢性腹泻的治疗
• JAMA：益生菌的服用与抗菌素使用所致的腹泻风险的降低有关 更多信息请点击：有关腹泻更多资讯

Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea.
Background & Aims
Variations in genes that regulate bile acid (BA) synthesis are associated with colonic transit in patients with irritable bowel syndrome (IBS). We investigated features of BA synthesis and excretion and genetic features of patients with different types of IBS.
Methods
In 26 healthy volunteers, 26 patients with IBS and constipation (IBS-C), and 26 with IBS and diarrhea (IBS-D), we measured serum levels of 7α-hydroxy-4-cholesten-3-one (C4; a surrogate for BA synthesis) and fibroblast growth factor (FGF) 19 (an ileal hormone that downregulates BA synthesis). For stool samples, we measured concentration of BA, weight, and amount of fat when participants were given high-fat diets. Spearman correlations were used to explore relationships among factors. We analyzed 1 polymorphism in Klotho-β (KLB) and 3 in fibroblast growth factor receptor-4 (FGFR4) for all members of each group using analysis of covariance.
Results
The concentration of BA in stool was associated with group (for a comparison of 3 groups; P = .057); it was higher in patients with IBS-D than IBS-C (P = .017). The serum level of C4 was higher in patients with IBS-D than IBS-C (P = .02) or healthy volunteers (P = .01); 38% of patients with IBS-D had increased serum levels of C4, compared with healthy volunteers. Serum level of C4 correlated with stool concentration of BA (rs = 0.606; P < .001), serum FGF19 (rs = −0.324; P = .007), and stool weight (rs = 0.366; P = .003). Stool concentration of BA correlated with weight (rs = 0.737; P < .001) and level of fat (rs = 0.528; P < .001). Body mass index correlated with serum level of C4 (rs = 0.423, P < .001) and stool concentration of BA (rs = 0.507, P < .001), and was higher in patients with IBS-D compared with other groups (overall P = .036). FGFR4 rs1966265 was associated with stool level of BA (P = .032).
Conclusions
Patients with IBS-D have greater body mass index and synthesize and excrete higher levels of BA than individuals with IBS-C or healthy volunteers. Serum levels of C4 might be used to identify patients with IBS-D who have BA malabsorption; studies are needed to determine if some patients have a genetic predisposition to this disorder.