Microbiome Transfer Partly Overrides Lack of IL‐1RI Signaling 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. The authors examine whether the metabolic phenotype of IL‐1RI−/− mice fed HFD or low‐fat diet (LFD) could be transferred to wild‐type (WT) mice through gut microbiome exchange facilitated by co‐housing.

Methods and results:
Male WT (C57BL/J6) and IL‐1RI−/− mice are 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 is dominant to WT, meaning that co‐housed WT mice adopted the IL‐1RI−/− microbiota profile. This is concomitant with greater body weight, hepatic lipid accumulation, adipocyte hypertrophy, and hyperinsulinemia in co‐housed WT mice, compared to single‐housed counterparts. These effects are most evident following HFD. Primary features of microbiome differences are Lachnospiraceae and Ruminococcaceae (known producers of SCFA).

Conclusion:
Transfer of SCFA‐producing microbiota from IL‐1RI−/− mice highlights a new connection between diet, inflammatory signaling, and the gut microbiome, an association that is dependent on the nature of the dietary fat challenge.