Gut microbiota dysfunction in Crohn's disease.

Introduction: Crohn's disease (CD) results from alterations in the gut microbiota and the immune system. However, the exact metabolic dysfunctions of the gut microbiota during CD are still unclear. Here, we investigated metagenomic functions using PICRUSt2 during the course of CD to better understand microbiota-related disease mechanisms and provide new insights for novel therapeutic strategies. Methods: We performed 16S rRNA-based microbial profiling of 567 faecal samples collected from a cohort of 383 CD patients, including 291 remissions (CR), 177 mild-moderate (CM) and 99 severe (CS) disease states. Gene and pathway composition was assessed using PICRUSt2 analyses of 16S data. Results: As expected, changes in alpha and beta diversity, in interaction networks and increases in Proteobacteria abundance were associated with disease severity. However, microbial function was more consistently disrupted than composition from CR, to CM and then to CS. Major shifts in oxidative stress pathways and reduced carbohydrate and amino acid metabolism in favour of nutrient transport were identified in CS compared to CR. Virulence factors involved in host invasion, host evasion and inflammation were also increased in CS. Conclusions: This functional metagenomic information provides new insights into community-wide microbial processes and pathways associated with CD pathogenesis. This study paves the way for new advanced strategies to rebalance gut microbiota and/or eliminate oxidative stress, and biofilm to downregulate gut inflammation.