DOP71 Fungal and bacterial gut microbiota in paediatric onset Inflammatory Bowel Disease introduced to infliximab
Ventin-Holmberg, R.(1);Höyhtyä, M.(2);Saqib, S.(3);Korpela, K.(3);Nikkonen, A.(4);Salonen, A.(3);de Vos, W.M.(5);Kolho, K.L.(6)
(1)University of Helsinki, Translational Immunology Research Program, Helsinki, Finland;(2)Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland;(3)University of Helsinki, Human Microbiome Research Program, Helsinki, Finland;(4)Helsinki University Hospital, University of Helsinki and Children´s Hospital, Helsinki, Finland;(5)University of Helsinki- Wageningen University, Human Microbiome Research Program- Laboratory of Microbiology, Helsinki, Finland;(6)University of Helsinki- Helsinki University Hospital, Translational Immunology Research Program- Human Microbiome Research Program- University of Helsinki and Children´s Hospital, Helsinki, Finland
Background
Paediatric Inflammatory Bowel Disease (PIBD), including Crohn’s Disease (CD), Ulcerative Colitis (UC) and IBD undefined (IBDU) is increasing worldwide and is characterized by an onset inflammation in the gastrointestinal tract. The patients may present severe symptoms such as abdominal pain, diarrhoea and bloody stool. No defined pathogenesis has been established for PIBD, but an imbalanced intestinal microbiota is strongly associated to the disease. Anti-tumour necrosis factor alpha (TNF-α) is an effective drug to treat inflammation in IBD, but up to half of the patients do not have a long-term response to the drug. Presently, there are no methods available to predict the TNF-α response. Here we have investigated the biomarkers of the gut fungal and bacterial microbiota, which are largely unexplored in paediatric patients, particularly for the fungal microbiota, with the aim to find possible predictors of drug response.
Methods
The gut microbiota composition of 30 PIBD (25 CD, 2 UC and 3 IBDU) patients at the Children´s Hospital, University of Helsinki receiving the anti-TNF-α drug infliximab (IFX) was studied by MiSeq sequencing targeting the bacterial 16S rRNA gene and fungal ITS region separately from faecal samples collected before the start of treatment and two and six weeks after treatment initiation. The response to IFX was evaluated by a faecal calprotectin value below 100 µg/g at week six after treatment initiation. The fungal MiSeq sequencing data was processed by using the DADA2 pipeline, annotated to the BLAST database and analysed using the package mare. The bacterial MiSeq sequencing data was analysed using mare and annotated to the SILVA database.
Results
Both the fungal and bacterial microbiota differed significantly between responders compared to non-responders to IFX, further validated by high predictive power (area under curve > 0.8) for therapy response. This difference was characterized by an increase in short-chain fatty acid producing bacteria, such as bacteria in the class Clostridia in the responders at baseline. This was observed as elevated Faecalibacterium and Subdoligranulum genera in particular of responders at baseline. Additionally, Candida was increased while Saccharomyces was decreased in non-responders at the end of the study. Finally, we observed that the interkingdom correlations differed between response groups to IFX.
Conclusion
Our results strengthen the proposal that the gut microbiota composition of PIBD patients could predict the response to anti-TNF-α treatment in the future.