Transfer of dysbiotic gut microbiota has beneficial effects on host liver metabolism

Abstract

Gut microbiota dysbiosis has been implicated in a variety of systemic disorders, notably metabolic diseases including obesity and impaired liver function, but the underlying mechanisms are uncertain. To investigate this question, we transferred caecal microbiota from either obese or lean mice to antibiotic‐free, conventional wild‐type mice. We found that transferring obese‐mouse gut microbiota to mice on normal chow (NC) acutely reduces markers of hepatic gluconeogenesis with decreased hepatic PEPCK activity, compared to non‐inoculated mice, a phenotypic trait blunted in conventional NOD2 KO mice. Furthermore, transferring of obese‐mouse microbiota changes both the gut microbiota and the microbiome of recipient mice. We also found that transferring obese gut microbiota to NC‐fed mice then fed with a high‐fat diet (HFD) acutely impacts hepatic metabolism and prevents HFD‐increased hepatic gluconeogenesis compared to non‐inoculated mice. Moreover, the recipient mice exhibit reduced hepatic PEPCK and G6Pase activity, fed glycaemia and adiposity. Conversely, transfer of lean‐mouse microbiota does not affect markers of hepatic gluconeogenesis. Our findings provide a new perspective on gut microbiota dysbiosis, potentially useful to better understand the aetiology of metabolic diseases. image Transfer of dysbiotic gut microbiota from obese to antibiotic‐free conventional mice changes gut microbiota and microbiome of recipient mice, ameliorates hepatic gluconeogenesis and prevents high‐fat diet‐induced dysmetabolism. Caecal microbiota transfer from obese to antibiotic‐free, conventional wild‐type mice lowers fasting glycaemia, reduces hepatic gluconeogenesis markers and gluconeogenic enzyme activity and changes both the gut microbiota and the microbiome. These affects are blunted in conventional NOD2 KO mice. Dysbiotic gut microbiota transfer prevents high‐fat diet‐induced dysmetabolism. The beneficial effects of dysbiotic gut microbiota transfers challenge the assumption that gut microbiota dysbiosis negatively affects metabolism.