The Gut Microbiota Affects Anti‐TNF Responsiveness by Activating the NAD+ Salvage Pathway in Ulcerative Colitis

Approximately 50% of the patients with ulcerative colitis (UC) are primarily nonresponsive to anti-tumor necrosis factor (TNF) therapy or lose their responsiveness over time. The gut microbiota plays an important role in the resistance of UC to anti-TNF therapy; however, the underlying mechanism remains unknown. Here, it is found that the transplantation of gut fecal microbiota from patients with UC alters the diversity of the gut microbiota in dextran sulfate sodium-induced colitis mice and may affect the therapeutic responsiveness of mice to infliximab. Furthermore, the abundances of Romboutsia and Fusobacterium increase in the tissues of patients with UC who do not respond to anti-TNF therapy. Differentially abundant metabolites are mainly enriched in nicotinate and nicotinamide metabolism in NCM460 cells after Fusobacterium nucleatum infection. Mechanistically, F. nucleatum promotes the nicotinamide adenine dinucleotide (NAD