Abstract
OBJECTIVES:
Beneficial
microbes and
probiotics are promising agents for the prevention and
treatment of enteric and
diarrheal diseases in children. However, little
is known about their in vivo mechanisms of action. We used a neonatal
mouse model of
rotavirus diarrhea to gain insight into how probiotics
ameliorate
acute gastroenteritis.
MATERIALS AND METHODS:
Rotavirus-infected
mice were treated with one of two strains of human-derived
Lactobacillus reuteri. We assessed intestinal microbiome composition
with 16S metagenomic sequencing,
enterocyte migration and proliferation
with
5-bromo-2'-deoxyuridine, and antibody and cytokine concentrations
with multiplex analyses of intestinal explant cultures.
RESULTS:
Probiotics
reduced diarrhea duration, improved intestinal histopathology, and
enhanced intestinal microbiome richness and phylogenetic diversity. The
magnitude of reduction of diarrhea by probiotics was strain-specific and
influenced by nutritional status. L. reuteri DSM 17938 reduced diarrhea
duration by zero, one, and two days in underweight, normal weight, and
overweight pups, respectively. The magnitude of reduction of diarrhea
duration correlated with increased enterocyte proliferation and
migration. Strain ATCC PTA 6475 reduced diarrhea duration by one day in
all mice without increasing enterocyte proliferation. Both probiotic
strains decreased concentrations of proinflammatory cytokines, including
MIP-1α and IL-1β, in all animals, and increased rotavirus-specific
antibodies in all but underweight animals. Body weight also influenced
the host response to rotavirus, in terms of diarrhea duration,
enterocyte turnover, and antibody production.
CONCLUSIONS:
These
data suggest that probiotic enhancement of enterocyte proliferation,
villus repopulation, and virus-specific antibodies may contribute to
diarrhea resolution, and that nutritional status influences the host
response to both beneficial microbes and pathogens.
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