Publication in detail

Immunity. 2017 Aug 15;47(2):339-348.e4. doi: 10.1016/j.immuni.2017.07.011. Epub 2017 Aug 8.

Nlrp6- and ASC-Dependent Inflammasomes Do Not Shape the Commensal Gut Microbiota Composition.

Mamantopoulos, M; Ronchi, F; Hauwermeiren, F Van; Vieira-Silva, S; Yilmaz, B; Martens, L; Saeys, Y; Drexler, SK; Yazdi, AS; Raes, J; Lamkanfi, M; McCoy, KD; Wullaert, A

Ghent University, Ghent, Belgium. VIB-UGent Center for Inflammation Research, VIB, Ghent, Belgium. University of Bern, Bern, Switzerland. Rega Institute, Leuven, Belgium. VIB-KU Leuven Center for Microbiology, VIB, Leuven, Belgium. VIB-UGent Center for Inflammation Research, VIB, Ghent, Belgium. University of Basel, Basel, Switzerland. University of Tübingen, Tübingen, Germany. University of Bern, Bern, Switzerland. University of Calgary, Calgary, AB, Canada.

Abstract:
The gut microbiota regulate susceptibility to multiple human diseases. The Nlrp6-ASC inflammasome is widely regarded as a hallmark host innate immune axis that shapes the gut microbiota composition. This notion stems from studies reporting dysbiosis in mice lacking these inflammasome components when compared with non-littermate wild-type animals. Here, we describe microbial analyses in inflammasome-deficient mice while minimizing non-genetic confounders using littermate-controlled Nlrp6-deficient mice and ex-germ-free littermate-controlled ASC-deficient mice that were all allowed to shape their gut microbiota naturally after birth. Careful microbial phylogenetic analyses of these cohorts failed to reveal regulation of the gut microbiota composition by the Nlrp6- and ASC-dependent inflammasomes. Our results obtained in two geographically separated animal facilities dismiss a generalizable impact of Nlrp6- and ASC-dependent inflammasomes on the composition of the commensal gut microbiota and highlight the necessity for littermate-controlled experimental design in assessing the influence of host immunity on gut microbial ecology.

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