Dietary fat and low fiber in purified diets differently impact the gut-liver axis to promote obesity-linked metabolic impairments.

Purified high-fat diets are commonly used to promote obesity and metabolic disturbances in animal models. However, most studies also use unpurified chow (low in fat, high in fiber content) as a "healthy" diet which can impact gut health. Here, we investigated the impact of feeding chow or purified diets varying in fat content on metabolic and intestinal functions in relation with temporal changes in gut microbiota composition. C57BL/6J male mice were fed either chow or purified low-fat (LF) or high-fat (HF) diet for 12 weeks. LF-fed mice displayed similar glucose and insulin homeostasis and bile acid profile than chow-fed mice but did exhibit higher fasting insulinemia and impaired insulin clearance, which was associated with increased weight gain and fat mass. Compared with chow, feeding LF or HF diets increased hepatic steatosis and inflammation, and impaired intestinal integrity. Changes in gut microbiota preceded these effects, with both purified diets inducing rapid and dramatic decrease of bacterial diversity and short chain fatty acid (SCFA) production. Importantly, branched SCFA levels increased only in HF-fed mice suggesting that this response is driven by excessive dietary fat rather than lack of fiber content. LF-fed mucus-associated microbial composition was also closer to that of chow-fed mice than that of HF-fed mice, suggesting the impact of fat content on this specific microbial community. We have identified distinct and overlapping gut microbiome and metabolic impairments caused by low fiber or high-fat contents in HF-fed animals, revealing their selective mechanisms underpinning the gastrointestinal and metabolic impacts in obesity.