Inflammatory Bowel Disease Unit, Department of Digestive Diseases, Sagunto Hospital, Av. Ramón y Cajal S/N, 46520, Sagunto, Valencia, Spain.
ADM-Lifesequencing S.L., University of Valencia Science Park, Carrer del Catedràtic Agustín Escardino Benlloch 9, Edificio 2, 46980, Paterna, Valencia, Spain.
Sci Rep. 2021 May 11;11(1):10016. doi: 10.1038/s41598-021-88823-2.
Intestinal dysbiosis is key in the onset and development of Crohn's disease (CD). We evaluated the microbiota changes in CD patients before and after a six-month anti-TNF treatment, comparing these changes with the microbiota of healthy subjects. This prospective multicenter observational study involved 27 CD patients initiating anti-TNF treatment and 16 healthy individuals. Inflammatory activity was determined at baseline, 3 and 6 months, classifying patients into responders and non-responders. Fecal microbiota was analyzed by massive genomic sequencing thought 16S rRNA amplicon sequencing before and after six months of anti-TNF treatment. The CD cohort showed a decrease in genera of the class Clostridia, short-chain fatty acid producers, and an increase in the phylum Proteobacteria (p < 0.01) versus the healthy cohort. After anti-TNF treatment, the phylum Proteobacteria also increased in non-responders versus responders (13/27) (p < 0.005), with the class Clostridia increasing. In addition, alpha diversity increased in responders versus non-responders (p < 0.01), tending towards eubiosis. An association was found (p < 0.001) in the F.prausnitzii/E.coli ratio between responders and non-responders. The F/E ratio was the most accurate biomarker of anti-TNF response (area under the curve 0.87). Thus, anti-TNF treatment allows partial restoration of intestinal microbiota in responders and the F.prausnitzii/E.coli ratio can provide a reliable indicator of response to anti-TNF in CD.
肠道菌群失调是克罗恩病（CD）发病和发展的关键。我们评估了 27 例接受抗 TNF 治疗的 CD 患者在治疗前和治疗后 6 个月的微生物群变化，并将这些变化与健康受试者的微生物群进行比较。这项前瞻性多中心观察性研究纳入了 27 例开始接受抗 TNF 治疗的 CD 患者和 16 例健康个体。在基线、3 个月和 6 个月时评估炎症活动，将患者分为应答者和无应答者。在接受抗 TNF 治疗前和治疗 6 个月后，通过 16S rRNA 扩增子测序对粪便微生物群进行了大规模基因组测序分析。与健康队列相比，CD 队列的 Clostridia 类、短链脂肪酸产生菌减少，变形菌门增加（p < 0.01）。在抗 TNF 治疗后，无应答者与应答者（13/27）相比，变形菌门也增加（p < 0.005），Clostridia 类增加。此外，应答者的 alpha 多样性高于无应答者（p < 0.01），趋向于真细菌。在应答者和无应答者之间发现了 F.prausnitzii/E.coli 比值的相关性（p < 0.001）。F/E 比值是抗 TNF 反应的最准确生物标志物（曲线下面积 0.87）。因此，抗 TNF 治疗可使应答者的肠道微生物群部分恢复，而 F.prausnitzii/E.coli 比值可提供 CD 对抗 TNF 反应的可靠指标。
