Abstract
The administration of prebiotics as oligosaccharides (OS), by acting on intestinal microbiota, could modulate the immune and inflammatory response and represent a new strategy to improve the outcome of bacterial infection. The aim of this study was to determine whether pectin-derived acidic oligosaccharides (pAOS) could modulate the outcome of pulmonary P. aeruginosa (PA) infection in C57BL/6 mice, which develop a Th1 response to PA lung infection. Mice were randomized for 5 weeks to consume a control or a 5% pAOS diet and chronically infected by PA. Resistance to a second PA infection was also analyzed by reinfecting the surviving mice 2 weeks after the first infection. Compared with control mice, mice fed pAOS had reduced mortality (P<0.05). This improvement correlated with a better control of the inflammatory response with a lower neutrophil count on day 1 (P<0.05), a sustained neutrophil and macrophage recruitment on days 2 and 3 (P<0.01) a greater and sustained IL-10 release in lung (P<0.05) and a reduction of the Th1 response and M1 activation with a lower IFN-γ/IL-4 (P<0.01) and nos2/arg1 (P<0.05) ratios. These results coincided with a modulation of the intestinal microbiota as shown by an increased butyric acid concentration in feces (P<0.05). Moreover, pAOS decreased the bacterial load (P<0.01) in mice reinfected 2 weeks after the first infection, suggesting that pAOS could reduce pulmonary exacerbations. In conclusion, pAOS improved the outcome of PA infection in C57BL/6 mice by modulating the intestinal microbiota and the inflammatory and immune responses.
Highlights
Dietary oligosaccharides (OSs) such as long-chain fructo-oligosaccharides and shortchain galacto-oligosaccharides are carbohydrate molecules with prebiotic properties [1]
The Short-chain fatty acids (SCFA) concentrations expressed as means and bacterial load, inflammatory and immune parameters expressed as medians were compared over time within the pectin-derived acidic oligosaccharides (pAOS) and control groups to assess the changes with time and between the two groups at the different times using the Mann–Whitney U test to assess the diet effect
The concentrations of SCFAs differed between the mice fed the control diet and those fed the pAOS diet from day 7 for the shortest SCFA acetic acid, day 14 for propionic and butyric acids, and day 21 for the longest SCFAs iso-valeric acid and valeric acid
Summary
Dietary oligosaccharides (OSs) such as long-chain fructo-oligosaccharides (lcFOS) and shortchain galacto-oligosaccharides (scGOS) are carbohydrate molecules with prebiotic properties [1]. OSs are degraded by intestinal microbiota into short-chain fatty acids (SCFAs) such as butyric acid and PLOS ONE | DOI:10.1371/journal.pone.0139686 November 23, 2015
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