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普拉梭菌定植与溃疡性结肠炎患者临床缓解维持

Colonisation by Faecalibacterium prausnitzii and maintenance of clinical remission in patients with ulcerative colitis.

机构信息

Department of Gastroenterology, Digestive System Research Unit, Institut de Recerca Vall d'Hebron, University Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Ciberehd, Barcelona, Spain.

出版信息

Aliment Pharmacol Ther. 2013 Jul;38(2):151-61. doi: 10.1111/apt.12365. Epub 2013 Jun 3.

DOI:10.1111/apt.12365
PMID:23725320
Abstract

BACKGROUND

Although incrimination of the intestinal microbiota in the pathogenesis of IBD is widely accepted, few data are available about the role of specific bacteria. Potentially, Faecalibacterium prausnitzii, bacteria with anti-inflammatory properties, might be deficient in ulcerative colitis (UC).

AIM

To quantify F. prausnitzii in the faecal microbiota of UC patients in remission and determine its relationship with relapse.

METHODS

A cross-sectional study included 116 UC patients in remission, 29 first-degree relatives and 31 healthy controls. A subset of eighteen patients, recruited during the first month of remission, underwent a 1-year follow-up. Total bacteria and F. prausnitzii were measured by quantitative Real Time PCR (qPCR, copies/g). Calprotectin was determined as inflammatory index (μg/g).

RESULTS

We found that F. prausnitzii was reduced in patients (median, IQR: 1.4 × 10⁸ , 5.1 × 10⁷-4.5 × 10⁸) and relatives (1.7 × 10⁸, 9.3 × 10⁷-5.1 × 10⁸) vs. controls (6.5 × 10⁸, 3.7 × 10⁸-1.6 × 10⁹, P < 0.0001). Moreover, low counts of F. prausnitzii were associated with less than 12 months of remission (8.0 × 10⁷, 2.0 × 10⁷-3.5 × 10⁸ vs. 2.1 × 10⁸, 1.0 × 10⁸-7.9 × 10⁸, P < 0.001) and more than 1 relapse/year (8.0 × 10⁷, 3.2 × 10⁷-3.8 × 10⁸ vs. 1.9 × 10⁸, 6.8 × 10⁷-6.0 × 10⁸, P < 0.01). When patients were followed up, F. prausnitzii increased steadily until reaching similar levels to those of controls if remission persisted (2.9 × 10⁸, 9.3 × 10⁶-1.2 × 10⁹; calprotectin: 76, 19-212), whereas it remained low if patients relapsed (2.2 × 10⁸, 1.4 × 10⁶-3.3 × 10⁸; calprotectin: 1760, 844-3662 P < 0.05 vs. controls).

CONCLUSIONS

Defective gut colonisation by F. prausnitzii occurred in UC patients during remission and in their unaffected relatives. The recovery of the F. prausnitzii population after relapse is associated with maintenance of clinical remission.

摘要

背景

虽然人们广泛接受肠道微生物群在 IBD 发病机制中的罪魁祸首,但关于特定细菌的作用的数据很少。具有抗炎特性的拟杆菌 Prausnitzii 可能在溃疡性结肠炎 (UC) 中缺乏。

目的

定量检测 UC 缓解期患者粪便微生物群中的 F. prausnitzii,并确定其与复发的关系。

方法

一项横断面研究包括 116 例 UC 缓解期患者、29 名一级亲属和 31 名健康对照者。在缓解期的第一个月招募了 18 名患者进行为期 1 年的随访。通过定量实时 PCR(qPCR,拷贝/g)测量总细菌和 F. prausnitzii。通过测定 calprotectin 作为炎症指标(μg/g)。

结果

我们发现 F. prausnitzii 在患者(中位数,IQR:1.4×10⁸,5.1×10⁷-4.5×10⁸)和亲属(1.7×10⁸,9.3×10⁷-5.1×10⁸)中减少与对照组(6.5×10⁸,3.7×10⁸-1.6×10⁹,P<0.0001)。此外,F. prausnitzii 的低计数与缓解时间少于 12 个月(8.0×10⁷,2.0×10⁷-3.5×10⁸与 2.1×10⁸,1.0×10⁸-7.9×10⁸,P<0.001)和每年复发>1次(8.0×10⁷,3.2×10⁷-3.8×10⁸与 1.9×10⁸,6.8×10⁷-6.0×10⁸,P<0.01)相关。当对患者进行随访时,如果缓解持续,F. prausnitzii 会稳定增加,直到达到与对照组相似的水平(2.9×10⁸,9.3×10⁶-1.2×10⁹;calprotectin:76,19-212),而如果患者复发,F. prausnitzii 则保持较低水平(2.2×10⁸,1.4×10⁶-3.3×10⁸;calprotectin:1760,844-3662 P<0.05 与对照组相比)。

结论

UC 患者在缓解期及其未受影响的亲属中存在 F. prausnitzii 肠道定植缺陷。复发后 F. prausnitzii 种群的恢复与临床缓解的维持有关。

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