Biologics and Bugs in IBD: Host-Microbe Interactions and Biologics

Review by Mr. Cass Condray (USA)

Study Summary 

Two clinical studies highlighted the maturing cycle of biologic agent treatment strategies in clinical practice, and a basic science study disentangled the interaction between the gut microbiota, bacteriophages and the host immune system were reviewed in a commentary.¹

The PROFILE study² demonstrated that a top-down approach of infliximab plus an immunomodulator was superior to accelerated step-up in the management of moderate-to-severe Crohn’s disease.

The head-to-head SEQUENCE study³ showed that risankizumab was non-inferior to ustekinumab for inducing clinical remission in moderate-to-severe Crohn’s disease after 24 weeks and endoscopic remission in 48 weeks.

In an exploration of the relationship between the gut microbiota and host inflammatory response⁴, in a healthy state, Bacteroides fragilis enhanced immunomodulatory effects, while this effect was lost when the gut mucosa was inflamed due to a less diverse microbiota.

Commentary 

Major advances in inflammatory bowel disease therapeutics have emerged in 2024, including treatment strategies with biologic agents and gut microbiota–bacteriophage–host interaction emerged as a new frontier to target.

Before 2024 and this comprehensive study¹, biologics for moderate to severe IBD were typically used only after failure of conventional treatments due to safety, cost, and limited trial data (“fail first” approach, or “step up therapy”). This study showed that an early, aggressive top-down approach with infliximab and immunomodulators led to significantly better steroid- and surgery-free outcomes than the traditional step-up strategy.

Citation

1. Katsidzira, L., Misselwitz, B. Biologic agents for IBD come of age as host–microbe interactions emerge. Nat Rev Gastroenterol Hepatol 2025; 22:94–95.
2. Noor, N. M. et al. A biomarker-stratified comparison of top-down versus accelerated step-up treatment strategies for patients with newly diagnosed Crohn’s disease (PROFILE): a multicentre, open-label randomised controlled trial. Lancet Gastroenterol. Hepatol. 2024;9:415–427.
3. Peyrin-Biroulet, L. et al. Risankizumab versus ustekinumab for moderate-to-severe Crohn’s disease. N. Engl. J. Med. 2024;391:213–223.
4. Carasso, S. et al. Inflammation and bacteriophages affect DNA inversion states and functionality of the gut microbiota. Cell Host Microbe 2024;32:322–334.E9 

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