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Intestinal helminths modulate allergic inflammation by altering microbial metabolism

Zaiss, Mario M. and Rapin, Alexis and Lebon, Luc and Dubey, Lalit Kumar and Mosconi, Ilaria and Sarter, Kerstin and Piersigilli, Alessandra and Menin, Laure and Walker, Alan W. and Rougemont, Jacques and Oonagh, Paerewick and Geldhof, Peter and McCoy, Kathleen D. and Macpherson, Andrew and Croese, John and Giacomin, Paul R. and Loukas, Alex and Junt, Tobias and Marsland, Benjamin and Harris, Nicola L. (2015) Intestinal helminths modulate allergic inflammation by altering microbial metabolism. Immunity.

Abstract

Intesitnal helminths have exerted strong evolutionary pressure on their mammalian host, and a wealth of epidemiological and expeirmental data support the view that these organisms can confer protection against a immune-mediated inflammatory diseases such as allergy. We explored the possibility that interactions between intestinal helminths and the bacterial microbiome may contribute to the potent immuno-modulatory potential of these organisms. Our expeirments demonstrate that chronic infection with the murine intestinal helminth Heligmosomoides polygyrus bakeri (Hpb) can impact on bacterial communities in the cecum. We further show that the intestinal microbiome is both necessary for Hpb- mediated attenuation of allergic asthma and that disease suppression can be transferred to naïve recipients through fecal transplantation. The immuno-modulatory capacity of helminth-altered intestinal bacterial communities correlated with increased levels short chain fatty acids (SCFA), and the ability of Hpb infection to suppress allergic asthma required host responsiveness to these bacterial metabolites via the G protein - coupled receptor (GPR) -41 (also called free fatty acid receptor 3 or FFAR3). The ability of intestinal helminths to alter the metabolic potential of bacterial communities was further demonstrated in diverse parasitic and host species, suggesting that it may represent an evolutionary conserved feature.

Item Type: Article
Date Deposited: 05 Nov 2015 00:45
Last Modified: 05 Nov 2015 00:45
URI: https://oak.novartis.com/id/eprint/23322

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