# Orally Administered Porcine Intestinal Lactobacilli Improve the Respiratory Innate Immune Response Against Streptococcus pneumoniae

## TL;DR

A specific strain of lactobacilli from pigs improves respiratory immunity in mice, reducing pneumonia severity without antibiotics.

## Contribution

Identifies a strain-specific lactobacillus (LAFF998) that enhances respiratory innate immunity via the gut–lung axis in a mouse model.

## Key findings

- Strain LAFF998 reduced lung bacterial burden and tissue damage in pneumococcal-infected mice.
- LAFF998 enhanced alveolar macrophage functionality and modulated cytokine production without excessive inflammation.
- Other L. salivarius strains failed to confer protection or modulate immune responses.

## Abstract

Respiratory infections are a major cause of disease in pigs, and new strategies are needed to enhance host resistance in a safe and practical manner and to avoid the overuse of antimicrobials. In this study, we evaluated whether lactobacilli isolated from the porcine intestinal tract could modulate respiratory immunity through the gut–lung axis, in an experimental mice model of pneumococcal infection. Among three Ligilactobacillus salivarius strains tested, only the orally administered strain LAFF998 improved resistance to pneumococcal infection, reducing lung bacterial burden and tissue damage while enhancing the functionality of alveolar macrophages. These findings demonstrate that immunomodulatory effects are strain-specific and identify L. salivarius LAFF998 as a promising immunobiotic candidate to strengthen respiratory innate immunity and prevent bacterial pneumonia in pigs.

Background: Respiratory bacterial infections represent a major health challenge in swine production, highlighting the need for novel immunomodulatory strategies that enhance host resistance. In this study, we investigated whether porcine intestinal lactobacilli could modulate the gut–lung axis and improve respiratory innate immunity in a mouse model of Streptococcus pneumoniae infection, as a surrogate of Streptococcus suis pneumonia. Methods: Three strains of Ligilactobacillus salivarius (LAFF998, LAFF1071, and LAFF1095) were orally administered to Swiss mice prior to pneumococcal challenge. The resistance to the infection, the lung damage and the respiratory innate immune response were evaluated. Results: Only strain LAFF998 significantly reduced pulmonary bacterial loads, prevented bacteremia, and attenuated lung injury. This protective effect was associated with selective modulation of respiratory immunity, characterized by reduced neutrophilic inflammation, increased lymphocyte recruitment, and enhanced activation of alveolar macrophages expressing MHC-II. LAFF998 markedly increased the production of IFN-β, IFN-γ, IL-6, IL-10, and IL-27 in the respiratory tract, without inducing excessive inflammatory damage. Ex vivo and in vitro analyses confirmed that alveolar macrophages from LAFF998-treated mice exhibited a primed phenotype with heightened cytokine responses to pneumococcal stimulation. In contrast, strains LAFF1071 and LAFF1095 failed to confer protection or significantly modulate respiratory immune responses. Conclusions: These findings demonstrate a strict strain-dependent effect among porcine L. salivarius isolates and identify LAFF998 as a potent immunobiotic capable of enhancing respiratory innate immunity through the gut–lung axis. This work supports further studies of LAFF998 as an immunobiotic strategy for the prevention of respiratory infections in pigs.