Alteration of gut microbiota in high-fat diet-induced obese mice using carnosic acid from rosemary.

Rosmarinus officinalis (rosemary) is widely used as a food ingredient. Rosemary extract (containing 40% carnosic acid) exhibited potent antiobesity activity. However, the relationship between carnosic acid (CA) and changes in the gut microbiota of high-fat diet (HFD)-induced obese mice has not been fully investigated. C57BL/6 mice were fed a normal diet, an HFD, or an HFD containing 0.1% or 0.2% CA for 10 weeks. CA exhibited promising antiobesity effects and caused marked alterations in the gut microbiota of HFD-induced obese mice. CA caused the prevalence of probiotics and functional bacteria, including Akkermansia muciniphila , Muribaculaceae unclassified , and Clostridium innocuum group, and inhibited diabetes-sensitive bacteria, including Proteobacteria and Firmicutes . The ratio of Firmicutes to Bacteroidetes was regulated by CA in a dose-dependent manner, decreasing it from 13.22% to 2.42%. Additionally, CA reduced bile acid-metabolizing bacteria, such as Bilophila , Clostridium , Lactobacillus , and Leuconostoc . The results of the linear discriminant analysis and effect size analysis indicated that CA attenuated the microbial changes caused by HFD. The high CA (HCA) group (HFD containing 0.2% CA) exhibited a greater abundance of Verrucomicrobiae (including Akkermansia muciniphila , genus Akkermansia , family Akkermansiaceae , and order Verrucomicrobiales ), Eubacterium , and Erysipelatoclostridium , and the low CA (LCA) group (HFD containing 0.1% CA) exhibited a greater abundance of Eisenbergiella , Intestinimonas , and Ruminococcaceae . Our results demonstrate that the antiobesity effects of CA might be strongly related to its prebiotic effects.