In the present preclinical intervention study we assessed whether therapeutic PACAP application starting 3 days after ileitis induction (i) resulted in disease-alleviating effects in the intestinal tract, (ii) was associated with distinct shifts in gut microbiota composition, and furthermore, (iii) whether potential PACAP-induced anti-inflammatory effect could also be observed in extra-intestinal organs or (iv) even in systemic compartments. The gene discussed is ADCYAP1; the disease is Crohn ileitis.