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 Akkermansia muciniphila bacteria on fatty liver disease. Five-week-old C57BL/6N mice were administered either phosphate-buffered saline (PBS; control) or A. muciniphila 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 Akkermansia muciniphila. The gut microbiome was analyzed in fecal samples. Oral administration of A. muciniphila significantly (P < 0.05) lowered serum triglyceride (TG) and alanine aminotransferase (ALT) levels in obese mice. Compared to the non-A. muciniphila-treated group, the expression of SREBP (regulator of TG synthesis in liver tissue) was decreased in the A. muciniphila-treated group. The expression of IL-6 in the liver of obese mice was decreased following the administration of A. muciniphila. Furthermore, alterations in the ratio of Firmicutes to Bacteroidetes and the decrease in bacterial diversity caused by the HFD were restored upon the administration of A. muciniphila. These results indicate that A. muciniphila prevents fatty liver disease in obese mice by regulating TG synthesis in the liver and maintaining gut homeostasis. IMPORTANCE This study investigated the effect of Akkermansia muciniphila on fatty liver disease. Although some research about the effects of A. muciniphila on host health has been published, study of the relationship between A. muciniphila administration and fatty liver, as well as changes in the gut microbiota, has not been conducted. In this study, we demonstrated that A. muciniphila prevented fatty liver disease by regulation of the expression of genes that regulate fat synthesis and inflammation in the liver.

Changes in the fecal bacterial microbiota associated with disease severity in alcoholic hepatitis patients

“…Its depletion has been implicated in obesity and fatty liver disease, and supplementation of Akkermansia has even been shown to decrease serum triglyceride and alanine aminotransferase levels in obese mice. 27 Recently, Addolorato et al published their findings of significant Akkermansia reduction in patients with alcohol use disorder, irrespective of the degree of liver disease. 28 In line, Grander et al found a depletion of Akkermansia in fecal samples from alcoholic hepatitis patients and Akkermansia supplementation protected mice against liver injury in experimental alcoholic liver disease.…”

The Gut Microbiota-Produced Indole-3-Propionic Acid Confers the Antihyperlipidemic Effect of Mulberry-Derived 1-Deoxynojirimycin

“…Due to the limitation of 16S rRNA pyrosequencing, we cannot identify the specific species that may produce IPA. However, Clostridium sporogenes is the only proved intestinal bacteria to produce IPA ( 32 ). Given the elevated growth of Clostridium XIVa induced by DNJ and its positive correlation with IPA content, we conclude that DNJ female specifically alters the composition of the gut microbiota, characterized by the enrichment of certain members in Clostridium XIVa, to stimulate IPA generation, ultimately ameliorating hyperlipidemia.…”

Gut Microbiome Contributes to Liver Fibrosis Impact on T Cell Receptor Immune Repertoire

“…A. muciniphila, considered a promising probiotic, is known to have important value in improving host metabolic functions and immune responses (Derrien et al, 2017;Plovier et al, 2017;Zhang et al, 2019). Recent studies support a protective effect of A. muciniphila against hepatic injury, steatosis, and neutrophil infiltration (Wu et al, 2017;Kim et al, 2020). A. muciniphila also protects against ethanol-induced gut leakiness, enhanced mucus thickness, and tight-junction expression (Grander et al, 2018).…”