Evaluation of changes in intestinal microbiota in Crohn’s disease patients after anti-TNF alpha treatment

• Published in: Scientific reports Vol. 11; no. 1; pp. 10016 - 11
• Main Authors: Sanchis-Artero, Laura, Martínez-Blanch, Juan Francisco, Manresa-Vera, Sergio, Cortés-Castell, Ernesto, Valls-Gandia, Marina, Iborra, Marisa, Paredes-Arquiola, Jose Maria, Boscá-Watts, Maia, Huguet, Jose Maria, Gil-Borrás, Rafael, Rodríguez-Morales, Josefa, Cortés-Rizo, Xavier
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.05.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326; 631/61; 692/4020; 692/699; 692/699/1503; Clostridia; Crohn's disease; Dysbacteriosis; E coli; Fecal microflora; Humanities and Social Sciences; Inflammation; Inflammatory bowel diseases; Intestinal microflora; Intestine; Microbiota; multidisciplinary; Observational studies; Proteobacteria; rRNA 16S; Science; Science (multidisciplinary); Tumor necrosis factor; Whole genome sequencing
• ISSN: 2045-2322; 2045-2322
• 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.