Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases

被引：817

作者：

Duboc, Henri ^{[1
,2
,3
]}

Rajca, Sylvie ^{[1
,2
,3
]}

Rainteau, Dominique ^{[1
,2
,4
,5
]}

Benarous, David ^{[6
]}

Maubert, Marie-Anne ^{[1
,2
,4
,5
]}

Quervain, Elodie ^{[1
,2
]}

Thomas, Ginette ^{[1
,2
,4
,5
]}

Barbu, Veronique ^{[4
,5
]}

Humbert, Lydie ^{[1
,2
,4
,5
]}

Despras, Guillaume ^{[2
]}

Bridonneau, Chantal ^{[7
]}

Dumetz, Fabien ^{[7
]}

Grill, Jean-Pierre ^{[1
,2
]}

Masliah, Joelle ^{[1
,2
,4
,5
]}

Beaugerie, Laurent ^{[1
,2
,3
]}

Cosnes, Jacques ^{[1
,2
,3
]}

Chazouilleres, Olivier ^{[8
]}

Poupon, Raoul ^{[8
]}

Wolf, Claude ^{[1
]}

Mallet, Jean-Maurice ^{[2
]}

Langella, Philippe ^{[7
]}

Trugnan, Germain ^{[1
,2
,4
,5
]}

Sokol, Harry ^{[1
,2
,3
]}

Seksik, Philippe ^{[1
,2
,3
]}

机构：

[1] INSERM, U1057, ERL, UMR 7203, Paris, France

[2] Ecole Normale Super, Lab Biomol, UMR 7203, F-75231 Paris, France

[3] Hop St Antoine, AP HP, Dept Gastroenterol & Nutr, F-75571 Paris 12, France

[4] Hop St Antoine, AP HP, Dept Biochim B, F-75571 Paris 12, France

[5] Hop St Antoine, AP HP, LCBGM, F-75571 Paris 12, France

[6] Mu Tis, Paris, France

[7] INRA, Inst MICALIS, MICA, Jouy En Josas, France

[8] Hop St Antoine, AP HP, Dept Hepatol, Ctr Natl Reference Malad Inflammatoires Voies Bil, F-75571 Paris 12, France

来源：

GUT | 2013年 / 62卷 / 04期

关键词：

TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; ULCERATIVE-COLITIS; LITHOCHOLIC ACID; FECAL MICROBIOTA; RECEPTOR; TGR5; ANTIBIOTICS; METABOLISM; MICROFLORA;

D O I：

10.1136/gutjnl-2012-302578

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

100201 [内科学];

摘要：

Objective Gut microbiota metabolises bile acids (BA). As dysbiosis has been reported in inflammatory bowel diseases (IBD), we aim to investigate the impact of IBD-associated dysbiosis on BA metabolism and its influence on the epithelial cell inflammation response. Design Faecal and serum BA rates, expressed as a proportion of total BA, were assessed by high-performance liquid chromatography tandem mass spectrometry in colonic IBD patients (42) and healthy subjects (29). The faecal microbiota composition was assessed by quantitative real-time PCR. Using BA profiles and microbiota composition, cluster formation between groups was generated by ranking models. The faecal BA profiles in germ-free and conventional mice were compared. Direct enzymatic activities of BA biotransformation were measured in faeces. The impact of BA on the inflammatory response was investigated in vitro using Caco-2 cells stimulated by IL-1 beta. Results IBD-associated dysbiosis was characterised by a decrease in the ratio between Faecalibacterium prausntizii and Escherichia coli. Faecal-conjugated BA rates were significantly higher in active IBD, whereas, secondary BA rates were significantly lower. Interestingly, active IBD patients exhibited higher levels of faecal 3-OH-sulphated BA. The deconjugation, transformation and desulphation activities of the microbiota were impaired in IBD patients. In vitro, secondary BA exerted anti-inflammatory effects, but sulphation of secondary BAs abolished their anti-inflammatory properties. Conclusions Impaired microbiota enzymatic activity observed in IBD-associated dysbiosis leads to modifications in the luminal BA pool composition. Altered BA transformation in the gut lumen can erase the anti-inflammatory effects of some BA species on gut epithelial cells and could participate in the chronic inflammation loop of IBD.

引用

页码：531 / 539

页数：9

共 55 条

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