Microbiome-metabolome generated bile acids gatekeep infliximab efficacy in Crohn’s disease Original paper

What was studied?

This study aimed to identify biomarkers that predict non-response to infliximab treatment in Crohn’s Disease (CD) patients by exploring gut microbiome and metabolome interactions. Researchers sought to characterize how these microbiome-metabolome signatures influence the immune system and therapeutic efficacy, specifically in terms of M1 macrophage suppression and regulatory T cell (Treg) dominance.

Who was studied?

The study involved 100 CD patients who were starting infliximab therapy, as well as a control group of 49 healthy individuals. The patients were followed over time to evaluate their responses to infliximab, while their baseline microbiome and metabolome were analyzed to understand factors associated with primary non-response to the treatment.

Most important findings

The study found that certain microbiome signatures and metabolites were strongly associated with treatment response. Specifically, a reduction in beneficial bacteria like Bifidobacterium and Faecalibacterium at baseline was linked to infliximab failure. The gut microbiome of non-responders showed increased levels of pro-inflammatory genera such as Escherichia and Shigella, while beneficial species were significantly depleted. Metabolomic analysis also highlighted that non-responders had lower levels of taurochenodeoxycholic acid (TCDCA), which is associated with the regulation of immune cells, including Tregs. Fecal microbiota transplantation (FMT) experiments confirmed that microbiota from non-responders exacerbated inflammation in mice, supporting the role of specific gut microbial communities in treatment resistance. Additionally, a machine learning model based on microbiome data was able to predict treatment outcomes with an accuracy of 80.5%.

Key implications

These findings suggest that baseline microbiome and metabolome profiles could serve as predictive biomarkers for infliximab efficacy in CD patients. The research emphasizes the role of the gut microbiota in modulating immune responses and the importance of bile acid metabolism in treatment outcomes. This could lead to more personalized treatment strategies for CD, enabling clinicians to identify potential non-responders early and consider alternative therapeutic approaches. Additionally, restoring beneficial bacteria and specific metabolites could improve treatment outcomes in the future.