Intestinal Lactobacillus johnsonii protects against neuroangiostrongyliasis in BALB/c mice through modulation of immune response

TL;DR

This study shows that Lactobacillus johnsonii in the gut can reduce brain inflammation and improve survival in mice infected with a parasitic worm, possibly by balancing immune responses.

Contribution

This is one of the first studies to investigate the gut microbiome in mice infected with Angiostrongylus cantonensis and suggests Lactobacillus as a potential probiotic treatment.

Findings

Lactobacillus johnsonii reduced neuroinflammation and improved survival in infected mice.

L. johnsonii increased IL-10 and decreased pro-inflammatory cytokines in the brain.

Microbiome-related metabolites were not linked to the observed immune changes.

Abstract

Neuroangiostrongyliasis is characterized by eosinophilic meningoencephalitis with a robust onset of severe neurological symptoms, by which immunological factors and peripheral metabolites have been postulated to affect the course of the disease. The gut-brain axis provides a bidirectional communication between the gut and the central nervous system, and therefore, understanding the gut microbiome may provide us with a deeper insight into the pathogenesis of angiostrongyliasis. Using 16S rRNA sequencing, we identified an increase in the abundance of different Lactobacillus species in Angiostrongylus cantonensis-infected mice, which was correlated to the disease severity. However, attempts to inoculate L. johnsonii into A. cantonensis-infected mice surprisingly revealed an improvement in neuroinflammation and prolonged survival. RNA sequencing suggested an immune-modulatory effect of L. johnsonii, which was confirmed by ELISA, showing increased levels of IL-10 and reduced levels of IL-2, IL-4, IL-5, and MCP-1 in the brain. Nevertheless, L. johnsonii-associated improvements were not associated with microbiome-related metabolites, as UHPLC-MS/MS analysis revealed no change in short-chain fatty acids, tryptophan metabolites, and bile acids. Our results suggest that while intestinal L. johnsonii appears to be linked to the progression of neuroangiostrongyliasis, these bacteria are likely attempting to modulate the dysregulated immune response to combat the disease. This is one of the first studies to investigate the gut microbiome in mice with A. cantonensis infection, which extends our knowledge from the microbiome-point-of-view of the pathogenesis of angiostrongyliasis and how the body defends against A. cantonensis. This work also extends to possible treatment approaches using L. johnsonii as probiotics.

The gut-brain axis provides a bidirectional communication between the gut and the central nervous system and, therefore, is related to multiple disease pathogenesis. This research aimed to analyze the microbiome change of mice with Angiostrongylus cantonensis infection. Our results suggested an increase in the abundance of Lactobacillus in A. cantonensis-infected mice, which was initially thought to be correlated with the disease severity. However, oral supplementation of Lactobacillus johnsonii surprisingly improved the disease and the survival of A. cantonensis-infected mice. Further analysis suggested that gavage of L. johnsonii increased IL-10 and decreased IL-2, IL-4, IL-5, and MCP-1 levels in the brain. Our results provide evidence of how the gut microbiome affects angiostrongyliasis and support that Lactobacillus may represent a potential probiotic that may improve angiostrongyliasis and may serve as a new treatment approach.

Figures