Gut microbiota from metabolic disease-resistant, macrophage-specific RIP140 knockdown mice improves metabolic phenotype and gastrointestinal integrity

Abstract

While fecal microbiota transplantation (FMT) presents an attractive therapeutic strategy, it remains unclear how to choose the microbiota repertoire that most effectively transfers benefit to recipients. We identified a beneficial taxonomic repertoire in a transgenic mouse model (RIP140mÏ •KD) which resists the development of high fat diet (HFD)-induced metabolic diseases due to enhanced anti-inflammation engineered by lowering receptor interacting protein (RIP140) expression in macrophage. We confirmed using FMT from HFD-fed RIP140mÏ •KD to wild type (WT) mice that recipient mice acquired the microbiota repertoire of donor mice. Importantly, FMT from RIP140mÏ •KD to WT not only effectively transferred the beneficial taxonomic repertoire to WT recipients, but also enabled recipient animals acquiring the anti-inflammatory status of RIP140mÏ •KD donor animals and avoid HFD-induced insulin resistance, which is associated with significantly improved intestinal integrity. We conclude that FMT can transfer not only microbiota but also the donors' intestinal innate immune status and improved intestinal integrity.