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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. [ABSTRACT FROM AUTHOR]

Scope: This multi-omic study investigates the bidirectional interactions between gut microbiota and silymarin metabolism, highlighting the differential effects across various age groups. Silymarin, the extract from Silybum marianum (milk thistle), is commonly used for its hepatoprotective effects., Methods and Results: An in vitro fermentation colon model was used with microbiota from 20 stool samples obtained from healthy donors divided into two age groups. A combination of three analytical advanced techniques, namely proton nuclear magnetic resonance ( 1 H NMR), next-generation sequencing (NGS), and liquid chromatography-mass spectrometry (LC-MS) was used to determine silymarin microbial metabolites over 24 h, overall metabolome, and microbiota composition. Silymarin at a low diet-relevant dose of 50 µg mL -1 significantly altered gut microbiota metabolism, reducing short-chain fatty acid (acetate, butyrate, propionate) production, glucose utilization, and increasing alpha-diversity. Notably, the study reveals age-related differences in silymarin catabolism. Healthy elderly donors (70-80 years) exhibited a significant increase in a specific catabolite associated with Oscillibacter sp., whereas healthy young donors (12-45 years) showed a faster breakdown of silymarin components, particularly isosilybin B, which is associated with higher abundance of Faecalibacterium and Erysipelotrichaceae UCG-003., Conclusion: This study provides insights into microbiome functionality in metabolizing dietary flavonolignans, highlighting implications for age-specific nutritional strategies, and advancing our understanding of dietary (poly)phenol metabolism., (© 2024 The Author(s). Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)