# Comparative Immunomodulatory Profiles of Bifidobacterium animalis subsp. lactis HOM2120 and Bifidobacterium longum subsp. longum HOM1190: Insights from Genomics, In Vitro, and In Vivo Studies

## TL;DR

This study compares two Bifidobacterium strains, HOM2120 and HOM1190, revealing how each modulates the immune system differently, with HOM2120 favoring cell-mediated immunity and HOM1190 favoring humoral immunity.

## Contribution

The study provides novel insights into strain-specific immunomodulatory mechanisms of Bifidobacterium through genomic, in vitro, and in vivo analyses.

## Key findings

- HOM2120 enhances phagocytosis and TNF-α production, favoring cell-mediated immune responses.
- HOM1190 induces higher IL-6 secretion and modulates PI3K–Akt signaling, supporting humoral immunity.
- In mice, HOM2120 enhances cellular immunity while HOM1190 boosts humoral immunity.

## Abstract

Bifidobacterium species are widely used as probiotics; yet their strain-specific immunomodulatory mechanisms remain incompletely defined. In this study, we characterized the probiotic properties and immunomodulatory activities of two genetically distinct strains, B. lactis HOM2120, isolated from human milk, and B. longum HOM1190, isolated from infant feces. Genomic analyses revealed strain-specific features associated with environmental resilience and probiotic functionalities, including acid and bile tolerance, pathogen inhibition, and adhesion to intestinal epithelial cells, which were confirmed by in vitro assays. In RAW264.7 macrophages, HOM2120 preferentially enhanced phagocytosis and TNF-α production, whereas HOM1190 induced higher IL-6 secretion, reflecting distinct strain-specific immunomodulatory patterns. Transcriptomic profiling and qRT-PCR validation revealed distinct molecular signatures underlying these effects. HOM2120 preferentially activated NF-κB and STAT3 signaling pathways and induced higher Tnf expression, suggesting a bias toward cell-mediated immune responses. In contrast, HOM1190 more strongly modulated the PI3K–Akt signaling axis and upregulated Il6 and Cd80 expression, supporting enhanced antigen presentation and humoral immune–associated responses. These strain-specific immunological tendencies were further validated in mice. HOM2120 predominantly enhanced delayed-type hypersensitivity responses, indicative of cellular immunity, whereas HOM1190 more effectively increased hemolytic activity and antibody-producing cell numbers, reflecting preferential activation of humoral immunity. Collectively, these results suggest that HOM2120 and HOM1190 are functionally distinct yet synergistic probiotic candidates, supporting their potential application as functional food ingredients or therapeutic adjuncts to modulate host immunity.