J Appl Biomed X:X | DOI: 10.32725/jab.2026.006

Evidence for bidirectional gut-spleen crosstalk in rodent models: scoping review of possible mechanisms and therapeutic implications

Teresa Lucretia ORCID...^{1, 2}, Dewi Kartikawati Paramita ORCID...¹, Rina Susilowati ORCID...^{1, *}

¹ Universitas Gadjah Mada, Faculty of Medicine, Public Health and Nursing, Department of Histology and Cell Biology, Yogyakarta, Indonesia

² Maranatha Christian University, Faculty of Medicine, Department of Histology, Bandung, Indonesia

Introduction: The gut-spleen axis has been proposed to link the gut environment with splenic immune regulation and systemic homeostasis. This scoping review examines this interaction in rodent models.

Methods: Following PRISMA-ScR guidelines, we analyzed literature (2015-2025) from PubMed, Scopus, and other major databases, including English-language rodent studies reporting gut and splenic outcomes.

Results: Analysis of 48 studies suggests that gut dysbiosis may alter splenic architecture and immune function mainly via microbial metabolites, particularly short-chain fatty acids. Limited evidence indicates that splenic dysfunction could impair gut barrier integrity. Systemic stressors (e.g., infection or allergy) may reinforce this bidirectional inflammatory loop. Microbiota-targeted therapies have been observed primarily through gut-initiated mechanisms. Vagus nerve-mediated signaling points to a gut-brain-spleen network, though its directional hierarchy remains unresolved.

Conclusion: Evidence supports a gut-spleen axis in rodents, with gut-derived microbial metabolites appearing to influence splenic immunity. Support for a reciprocal spleen-to-gut pathway remains limited and emergent, highlighting a research asymmetry. Together, these interactions suggest a partially bidirectional network linking the gut ecosystem to systemic immunity, with additional neural integration extending this framework toward a gut-brain-spleen axis. This integrative model proposes the gut-spleen axis as a potential therapeutic target warranting further investigation in inflammatory, metabolic, and neurological diseases.

Keywords: Gut dysbiosis; Gut-spleen axis; Microbial metabolites; Neuroimmunology; Splenic immunity

Grants and funding:

This study was supported by a grant from the Maranatha Christian University Foundation number 004/PEG-PRJ/SL-YPTKM/UKM/VIII/2021.

Conflicts of interest:

The authors have no conflict of interest to declare.

Received: October 12, 2025; Revised: May 19, 2026; Accepted: May 21, 2026; Prepublished online: June 11, 2026