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PLoS Negl Trop Dis. 2017 Apr 19;11(4):e0005548. doi: 10.1371/journal.pntd.0005548. eCollection 2017 Apr.

The gut microbiota as a modulator of innate immunity during melioidosis.

Author information

1
Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
2
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
3
Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
4
Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
5
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
6
Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center, Amsterdam, The Netherlands.
7
Department of Medical Microbiology, Vrije Universiteit, Amsterdam, The Netherlands.

Abstract

BACKGROUND:

Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an emerging cause of pneumonia-derived sepsis in the tropics. The gut microbiota supports local mucosal immunity and is increasingly recognized as a protective mediator in host defenses against systemic infection. Here, we aimed to characterize the composition and function of the intestinal microbiota during experimental melioidosis.

METHODOLOGY/PRINCIPAL FINDINGS:

C57BL/6 mice were infected intranasally with B. pseudomallei and sacrificed at different time points to assess bacterial loads and inflammation. In selected experiments, the gut microbiota was disrupted with broad-spectrum antibiotics prior to inoculation. Fecal bacterial composition was analyzed by means of IS-pro, a 16S-23S interspacer region-based profiling method. A marked shift in fecal bacterial composition was seen in all mice during systemic B. pseudomallei infection with a strong increase in Proteobacteria and decrease in Actinobacteria, with an increase in bacterial diversity. We found enhanced early dissemination of B. pseudomallei and systemic inflammation during experimental melioidosis in microbiota-disrupted mice compared with controls. Whole-genome transcriptional profiling of the lung identified several genes that were differentially expressed between mice with a normal or disrupted intestinal microbiota. Genes involved in acute phase signaling, including macrophage-related signaling pathways were significantly elevated in microbiota disrupted mice. Compared with controls, alveolar macrophages derived from antibiotic pretreated mice showed a diminished capacity to phagocytose B. pseudomallei. This might in part explain the observed protective effect of the gut microbiota in the host defense against pneumonia-derived melioidosis.

CONCLUSIONS/SIGNIFICANCE:

Taken together, these data identify the gut microbiota as a potential modulator of innate immunity during B. pseudomallei infection.

PMID:
28422970
PMCID:
PMC5411098
DOI:
10.1371/journal.pntd.0005548
[Indexed for MEDLINE]
Free PMC Article

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