Impact of Periodontal Host-Modulation Therapies on Oral–Gut Microbiome Axis in Periodontitis Patients with Hematological Diseases: A Narrative Review

Host-modulating therapies and oral microbiome-targeted approaches are emerging options in periodontal care and are especially relevant for patients undergoing immunotherapy for hematologic malignancies. Immune dysregulation induced by immune checkpoint inhibitors or CAR-T cell therapy may worsen periodontal inflammation and alter the composition and functions of the oral microbiota. Beyond these, other immunomodulatory treatments commonly employed in hematologic malignancies—including monoclonal antibodies (e.g., rituximab, daratumumab), immunomodulatory drugs (e.g., lenalidomide, thalidomide), cytokine-based therapies (e.g., interferon-α), and targeted small-molecule inhibitors (e.g., BTK inhibitors, JAK inhibitors) may also influence periodontal homeostasis and oral microbial ecology by altering neutrophil function, cytokine profiles, and mucosal immune surveillance. The oral microbiota is functionally connected with the intestinal microbial ecosystem through the oral–gut axis, by periodontal pathogens may colonize the gut and modulate systemic immune responses, with potential repercussions on the efficacy and safety of immunotherapy. This narrative review examines the mechanisms and clinical applicability of host-modulating therapies, including subantimicrobial-dose doxycycline, omega-3 fatty acids, and microbiome-targeted interventions, such as oral probiotics, prebiotics and other antimicrobials in patients treated with immunotherapy.