BACKGROUND AND AIMS: 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]. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Department of Food Science Faculty of Agrobiology Food and Natural Resources Czech Univesity of Life Sciences Prague Czechia

Department of Medical Microbiology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Department of Paediatric Surgery 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Department of Paediatrics 1st Faculty of Medicine Charles University and Thomayer University Hospital Prague Czechia

Department of Paediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Department of Paediatrics Faculty of Medicine in Pilsen Charles University and University Hospital Pilsen Czechia

Department of Paediatrics Faculty of Medicine Palacky University Olomouc and University Hospital Olomouc Czechia

Department of Paediatrics Masaryk Hospital Usti nad Labem Czechia

Department of Paediatrics Tomas Bata Hospital Zlin Czechia

Department of Pediatric and Adult Rheumatology Motol University Hospital Prague Czechia

Synlab Czech Inc Prague Czechia

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$a Hurych, Jakub $u Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia $u Department of Paediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia $1 https://orcid.org/0000000298135290

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$a Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease / $c J. Hurych, A. Mascellani Bergo, T. Lerchova, L. Hlinakova, M. Kubat, H. Malcova, D. Cebecauerova, J. Schwarz, E. Karaskova, T. Hecht, R. Vyhnanek, L. Toukalkova, V. Dotlacil, K. Greinerova, A. Cizkova, R. Horvath, J. Bronsky, J. Havlik, O. Hradsky, O. Cinek

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$a BACKGROUND AND AIMS: 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]. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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$a Mascellani Bergo, Anna $u Department of Food Science, Faculty of Agrobiology, Food and Natural Resources, Czech Univesity of Life Sciences, Prague, Czechia

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$a Lerchova, Tereza $u Department of Paediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia

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$a Kubat, Michal $u Department of Paediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia

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$a Malcova, Hana $u Department of Pediatric and Adult Rheumatology, Motol University Hospital, Prague, Czechia

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$a Cebecauerova, Dita $u Department of Pediatric and Adult Rheumatology, Motol University Hospital, Prague, Czechia

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$a Schwarz, Jan $u Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University and University Hospital Pilsen, Czechia

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$a Karaskova, Eva $u Department of Paediatrics, Faculty of Medicine, Palacky University Olomouc and University Hospital Olomouc, Czechia

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$a Hecht, Tomas $u Department of Paediatrics, 1st Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czechia

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$a Vyhnanek, Radim $u Department of Paediatrics, 1st Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czechia

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$a Toukalkova, Lenka $u Department of Paediatrics, Tomas Bata Hospital, Zlin, Czechia

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$a Horvath, Rudolf $u Department of Pediatric and Adult Rheumatology, Motol University Hospital, Prague, Czechia

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$a Bronsky, Jiri $u Department of Paediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia $1 https://orcid.org/0000000226417280

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$a Havlik, Jaroslav $u Department of Food Science, Faculty of Agrobiology, Food and Natural Resources, Czech Univesity of Life Sciences, Prague, Czechia

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$a Cinek, Ondrej $u Department of Medical Microbiology, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia $u Department of Paediatrics, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czechia

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