Jakub Hurych, Anna Mascellani Bergo, Tereza Lerchova, Lucie Hlinakova, Michal Kubat, Hana Malcova, Dita Cebecauerova, Jan Schwarz, Eva Karaskova, Tomas Hecht, Radim Vyhnanek, Lenka Toukalkova, Vojtech Dotlacil, Katerina Greinerova, Anabela Cizkova, Rudolf Horvath, Jiri Bronsky, Jaroslav Havlik, Ondrej Hradsky, Ondrej Cinek. Journal of Crohn's and Colitis. August 2023. IF: 8. doi
MUDr. Jakub Hurych, Department of Medical Microbiology, Second Faculty of Medicine and Motol University Hospital
Abstract
Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn’s disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA].
Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab.
We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test.
Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.
