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Sci Rep. 2016 Nov 29;6:37944. doi: 10.1038/srep37944.

Impact of the microbial derived short chain fatty acid propionate on host susceptibility to bacterial and fungal infections in vivo.

Author information

1
Infectious Diseases Service and Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, 1066, Switzerland.
2
Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Epalinges, 1066, Switzerland.

Abstract

Short chain fatty acids (SCFAs) produced by intestinal microbes mediate anti-inflammatory effects, but whether they impact on antimicrobial host defenses remains largely unknown. This is of particular concern in light of the attractiveness of developing SCFA-mediated therapies and considering that SCFAs work as inhibitors of histone deacetylases which are known to interfere with host defenses. Here we show that propionate, one of the main SCFAs, dampens the response of innate immune cells to microbial stimulation, inhibiting cytokine and NO production by mouse or human monocytes/macrophages, splenocytes, whole blood and, less efficiently, dendritic cells. In proof of concept studies, propionate neither improved nor worsened morbidity and mortality parameters in models of endotoxemia and infections induced by gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae), gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) and Candida albicans. Moreover, propionate did not impair the efficacy of passive immunization and natural immunization. Therefore, propionate has no significant impact on host susceptibility to infections and the establishment of protective anti-bacterial responses. These data support the safety of propionate-based therapies, either via direct supplementation or via the diet/microbiota, to treat non-infectious inflammation-related disorders, without increasing the risk of infection.

PMID:
27897220
PMCID:
PMC5126587
DOI:
10.1038/srep37944
[Indexed for MEDLINE]
Free PMC Article

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