Marine-Derived Functional Foods for Host-Directed Tuberculosis Therapy: Immunomodulatory Mechanisms and Host-Pathogen Crosstalk

Tuberculosis (TB) remains a global health challenge, motivating research into marine-derived compounds as potential host-directed adjuncts. This systematic review synthesized seven eligible experimental studies identified through a semantic literature search, evaluating omega-3 polyunsaturated fatty acids (PUFAs), fucoxanthin, caulerpin, and fucoidan. Findings were synthesized narratively because methodological heterogeneity precluded meta-analysis. No included study directly evaluated marine-derived peptides or peptide hydrolysates. Caulerpin reduced intracellular Mycobacterium tuberculosis burden, but its NLRP3 and cytokine effects were examined in a non-tuberculous mycobacterial model. Fucoxanthin-containing fractions demonstrated direct antimycobacterial activity and reduced organ bacterial burden without establishing a causal host-directed pathway in TB. Fucoidan microparticles supported drug delivery; growth inhibition was demonstrated for an isoniazid/rifabutin-containing formulation, without establishing an independent fucoidan effect. Omega-3 PUFAs yielded contradictory findings, impairing macrophage antimicrobial activity in vitro while reducing bacterial burden in some animal models. Differences in host species, nutritional status, granuloma pathology, and intervention timing may explain these discrepancies. Marine-derived compounds show preliminary potential, but host-associated outcomes, direct antimicrobial activity, and formulation effects require separate interpretation. Heterogeneous preclinical designs and limited safety evidence constrain translation. Further research should establish TB-specific mechanisms, evaluate safety, and investigate peptides and adjunctive combinations with conventional therapy.