Akkermansia muciniphila Prevents Fatty Liver Disease, Decreases Serum Triglycerides, and Maintains Gut Homeostasis

Abstract

The objective of this study was to elucidate the effect of intestinal <i>Akkermansia muciniphila</i> bacteria on fatty liver disease. Five-week-old C57BL/6N mice were administered either phosphate-buffered saline (PBS; control) or <i>A. muciniphila</i> at 10⁸ to 10⁹ CFU/ml, and were fed either a 45% fat diet (high-fat diet [HFD]) or a 10% fat diet (normal diet [ND]) for 10 weeks. After 10 weeks, the mice were euthanized, and blood and tissue samples, including adipose tissue, cecum, liver, and brain, were immediately collected. Biochemical and histological analyses were conducted, and the expression levels of related factors were compared to determine the antiobesity effects of <i>Akkermansia muciniphila</i> The gut microbiome was analyzed in fecal samples. Oral administration of <i>A. muciniphila</i> significantly (<i>P</i> < 0.05) lowered serum triglyceride (TG) and alanine aminotransferase (ALT) levels in obese mice. Compared to the non-<i>A. muciniphila</i>-treated group, the expression of <i>SREBP</i> (regulator of TG synthesis in liver tissue) was decreased in the <i>A. muciniphila</i>-treated group. The expression of <i>IL-6</i> in the liver of obese mice was decreased following the administration of <i>A. muciniphila</i> Furthermore, alterations in the ratio of <i>Firmicutes</i> to <i>Bacteroidetes</i> and the decrease in bacterial diversity caused by the HFD were restored upon the administration of <i>A. muciniphila</i> These results indicate that <i>A. muciniphila</i> prevents fatty liver disease in obese mice by regulating TG synthesis in the liver and maintaining gut homeostasis.<b>IMPORTANCE</b> This study investigated the effect of <i>Akkermansia muciniphila</i> on fatty liver disease. Although some research about the effects of <i>A. muciniphila</i> on host health has been published, study of the relationship between <i>A. muciniphila</i> administration and fatty liver, as well as changes in the gut microbiota, has not been conducted. In this study, we demonstrated that <i>A. muciniphila</i> prevented fatty liver disease by regulation of the expression of genes that regulate fat synthesis and inflammation in the liver.