Microbiome Transfer Partly Overrides Lack of IL-1RI Signalling to Alter Hepatic but not Adipose Tissue Phenotype and Lipid Handling following a High-Fat Diet Challenge.

SCOPE IL-1RI-mediated inflammatory signaling alters metabolic tissue responses to dietary challenges (e.g. high-fat diet (HFD)). Recent work suggests that metabolic phenotype is transferrable between mice in a shared living environment (i.e. co-housing) due to gut microbiome exchange. We examined whether the metabolic phenotype of IL-1RI-/- mice fed HFD or low-fat diet (LFD) could be transferred to wildtype (WT) mice through gut microbiome exchange facilitated by co-housing. METHODS AND RESULTS Male WT (C57BL/J6) and IL-1RI-/-  mice were fed HFD (45% kcal) or LFD (10% kcal) for 24 weeks and housed i) by genotype (single-housed) or ii) with members of the other genotype in a shared microbial environment (co-housed). The IL-1RI-/-  gut microbiome was dominant to WT, meaning that co-housed WT mice adopted the IL-1RI-/- microbiota profile. This was concomitant with greater body weight, hepatic lipid accumulation, adipocyte hypertrophy and hyperinsulinemia in co-housed WT mice, compared to single-housed counterparts. These effects were most evident following HFD. Primary features of microbiome differences were Lachnospiraceae and Ruminococcaceae (known producers of SCFA). CONCLUSION Transfer of SCFA-producing microbiota from IL-1RI-/-  mice highlights a new connection between diet, inflammatory signalling and the gut microbiome, an association that is dependent on the nature of the dietary fat challenge. This article is protected by copyright. All rights reserved.