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肠易激综合征中胆汁酸代谢与微生物群之间的相互作用。

Interplay between bile acid metabolism and microbiota in irritable bowel syndrome.

作者信息

Dior M, Delagrèverie H, Duboc H, Jouet P, Coffin B, Brot L, Humbert L, Trugnan G, Seksik P, Sokol H, Rainteau D, Sabate J-M

机构信息

ERL U1157/UMR 7203. Inserm, Paris VI University, Paris, France.

Department of Gastroenterology, Louis Mourier Hospital, AP-HP, Colombes, France.

出版信息

Neurogastroenterol Motil. 2016 Sep;28(9):1330-40. doi: 10.1111/nmo.12829. Epub 2016 Apr 5.

Abstract

BACKGROUND

Irritable bowel syndrome (IBS) physiopathology is multifactorial and roles for both microbiota and bile acid (BA) modifications have been proposed. We investigated role of dysbiosis, transit pattern and BA metabolism in IBS.

METHODS

Clinical data, serum, and stool samples were collected in 15 healthy subjects (HS), 16 diarrhea-predominant (IBS-D) and 15 constipation-predominant IBS (IBS-C). Fecal microbiota composition was analyzed by real-time PCR. Sera and fecal BA profiles, 7α-C4 levels, and in vitro BA transformation activity by fecal microbiota were measured by mass spectrometry. Serum Fibroblast Growth Factor 19 (FGF19) was assayed by ELISA.

KEYS RESULTS

Dysbiosis was present in IBS patients with an increase in Escherichia coli in IBS-D patients (p = 0.03), and an increase in Bacteroides (p = 0.01) and Bifidobacterium (p = 0.04) in IBS-C patients. Sera primary and amino-conjugated BA were increased in IBS-D (63.5 ± 5.5%, p = 0.01 and 78.9 ± 6.3%, p = 0.03) and IBS-C patients (55.9 ± 5.5%, p = 0.04 and 65.3 ± 6.5%, p = 0.005) compared to HS (37.0 ± 5.8% and 56.7 ± 8.1%). Serum 7α-C4 and FGF19 levels were not different among all three groups. Fecal primary BA were increased in IBS-D patients compared to HS, including chenodeoxycholic acid which has laxative properties (25.6 ± 8.5% vs 3.5 ± 0.6%, p = 0.005). Bile acid deconjugation activity was decreased in IBS-D (p = 0.0001) and IBS-C (p = 0.003) feces. Abdominal pain was positively correlated with serum (R = 0.635, p < 0.001) and fecal (R = 0.391, p = 0.024) primary BA.

CONCLUSIONS & INFERENCES: Different sera and fecal BA profiles in IBS patients could be secondary to dysbiosis and further differences between IBS-C and IBS-D could explain stool patterns. This study opens new fields in IBS physiopathology and suggests that modification of BA profiles could have therapeutic potential.

摘要

背景

肠易激综合征(IBS)的病理生理学是多因素的,微生物群和胆汁酸(BA)修饰的作用都已被提出。我们研究了IBS中微生物失调、转运模式和BA代谢的作用。

方法

收集了15名健康受试者(HS)、16名腹泻型(IBS-D)和15名便秘型IBS(IBS-C)患者的临床数据、血清和粪便样本。通过实时PCR分析粪便微生物群组成。用质谱法测量血清和粪便BA谱、7α-C4水平以及粪便微生物群的体外BA转化活性。用ELISA法检测血清成纤维细胞生长因子19(FGF19)。

主要结果

IBS患者存在微生物失调,IBS-D患者大肠杆菌增加(p = 0.03),IBS-C患者拟杆菌(p = 0.01)和双歧杆菌增加(p = 0.04)。与HS(37.0±5.8%和56.7±8.1%)相比,IBS-D(63.5±5.5%,p = 0.01和78.9±6.3%,p = 0.03)和IBS-C患者(55.9±5.5%,p = 0.04和65.3±6.5%,p = 0.005)的血清初级和氨基共轭BA增加。三组之间血清7α-C4和FGF19水平无差异。与HS相比,IBS-D患者粪便中的初级BA增加,包括具有泻药特性的鹅去氧胆酸(25.6±8.5%对3.5±0.6%,p = 0.005)。IBS-D(p = 0.0001)和IBS-C(p = 0.003)粪便中的胆汁酸去结合活性降低。腹痛与血清(R = 0.635,p < 0.001)和粪便(R = 0.391,p = 0.024)初级BA呈正相关。

结论与推论

IBS患者不同的血清和粪便BA谱可能继发于微生物失调,IBS-C和IBS-D之间的进一步差异可以解释大便模式。本研究为IBS病理生理学开辟了新领域,并表明BA谱的改变可能具有治疗潜力。

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