Shaping of Intestinal Microbiota in Nlrp6- and Rag2-Deficient Mice Depends on Community Structure

Cell Rep. 2017 Dec 26;21(13):3914-3926. doi: 10.1016/j.celrep.2017.12.027.

Abstract

Contradicting observations have been made regarding the relative contributions of immune sensors to shaping the microbiome, yet the reasons for these discrepancies are not fully understood. Here, we investigated the contribution of environmental factors in shaping the microbiome in mice deficient in adaptive immunity (Rag2-/-) and Nlrp6, an immune sensor proposed to be involved in regulation of microbiota composition. In conventionally housed Nlrp6-/- mice, familial transmission has a significant effect on microbiota composition, complicating the analysis of genotype-dependent effects. Notably, after rederivation into standardized specific pathogen-free (SPF) conditions devoid of pathobionts, microbiota composition was indistinguishable between WT, Rag2-/-, and Nlrp6-/- mice. However, upon reintroduction of a pathobiont-containing community host, genotype-dependent differences reappear, specifically affecting the relative abundance of pathobionts such as Helicobacter spp. Our results show that the impact of Nlrp6 and also of adaptive immunity on microbiota composition depends on community structure and primarily influences pathobionts but not commensals.

Keywords: Nlrp6; adaptive immunity; familial transmission; gut biogeography; host-microbiota interaction; intestinal microbiota.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / metabolism
  • Gastrointestinal Microbiome* / genetics
  • Genotype
  • Inflammasomes
  • Mice, Inbred C57BL
  • Microbiota*
  • Receptors, Cell Surface / metabolism*
  • Specific Pathogen-Free Organisms

Substances

  • DNA-Binding Proteins
  • Inflammasomes
  • Nod-like receptor pyrin domain-containing protein 6, mouse
  • Rag2 protein, mouse
  • Receptors, Cell Surface