Corynebacterium pseudotuberculosis
(
C. p
), a facultative intracellular bacterium, is an important zoonotic pathogen that causes abscesses and pyogenic granulomas. The relationship between gut microbiota and host health or diseases has received increasing attention. However, the role of gut microbiota in the process of
C. p
infection is still unclear. In this study, we established a
C. p
infection model in C57BL/6 mice and examined the impact of preemptive oral administration
Lactobacillus acidophilus
(
L. acidophilus
) on infection. Our findings revealed that
C. p
infection led to pronounced pathological alterations in the liver and kidneys, characterized by abscess formation, intense inflammatory responses, and bacterial overload. Remarkably, these deleterious effects were greatly relieved by oral administration of
L. acidophilus
before infection with
C. p
. Additionally, we further found that during
C. p
infection, peritoneal macrophages (PMs) of mice orally administered with
L. acidophilus
accumulated more rapidly at sites of infection. Furthermore, our results showed that PMs from mice with oral
L. acidophilus
administration showed a stronger
C. p
clearance effect, and this was mediated by high expression of LC3-II protein. Meanwhile, oral administration of
L. acidophilus
protected the gut microbiota disorder in C57BL/6 mice caused by
C. p
infection. In summary, our study demonstrates that oral administration of
L. acidophilus
confers effective protection against
C. p
infection in C57BL/6 mice by modulating macrophage autophagy, thereby augmenting bacterial clearance and preserving gut microbiota and function stability. These findings position
L. acidophilus
as a viable probiotic candidate for the clinical prevention of
C. p
infection.
IMPORTANCE
Corynebacterium pseudotuberculosis
(C.
p
) is known to induce a range of chronic diseases in both animals and humans. Currently, clinical treatment for C.
p
infection mainly relies on antibiotic therapy or surgical intervention. However, excessive use of antibiotics may increase the risk of drug-resistant strains, and the effectiveness of treatment remains unsatisfactory. Furthermore, surgical procedures do not completely eradicate pathogens and can easily cause environmental pollution. Probiotic interventions are receiving increasing attention for improving the body’s immune system and maintaining health. In this study, we established a C.
p
infection model in C57BL/6 mice to explore the impact of
Lactobacillus
acidophilus during C.
p
infection. Our results showed that
L. acidophilus
effectively protected against C.
p
infection by regulating the autophagy of macrophages and maintaining intestinal microbiota homeostasis. This study may provide a new strategy for the prevention of C.
p
infection.