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. 2020 Nov 9;12(1):1830693.
doi: 10.1080/19490976.2020.1830693.

Therapeutic manipulation of gut microbiota by polysaccharides of Wolfiporia cocos reveals the contribution of the gut fungi-induced PGE2 to alcoholic hepatic steatosis

Shanshan Sun  1   2 , Kai Wang  1 , Li Sun  1   3 , Baosong Cheng  1   3 , Shanshan Qiao  1   3 , Huanqin Dai  1 , Wenyu Shi  4 , Juncai Ma  4 , Hongwei Liu  1   2   3
Affiliations

Therapeutic manipulation of gut microbiota by polysaccharides of Wolfiporia cocos reveals the contribution of the gut fungi-induced PGE2 to alcoholic hepatic steatosis

Shanshan Sun et al. Gut Microbes. .

Abstract

Alcohol abuse and alcoholic liver diseases (ALD) have been worldwide spread. Chronic alcoholism-induced overgrowth of intestinal bacteria and fungi together with the enteric dysbiosis are important pathogenic mechanisms in ALD. We demonstrated that the water-insoluble polysaccharides (WIP) from Wolfporia cocos effectively ameliorated the hepatic inflammatory injury and fat accumulation through modulating gut microbiota in mice with alcoholic hepatic steatosis (AHS). Oral administration of WIP significantly enhanced the ratio of Firmictues to Proteobacteria, increased the abundance of Lachnospiraceae including Ruminoclostridum and unidentified_clostridials, and inhibited the ethanol-induced fungal overgrowth. Treatment with WIP activated the PPAR-γ signaling and reduced the inflammation in the colonic epithelia cell, facilitating a hypoxic state that suppresses the overgrowth of fungi and Proteobacteria in the gut. In addition, we found an overwhelming increase of the commensal fungus Meyerozyma guilliermondii in the feces of mice with AHS by culturing and ITS sequencing. Inoculation of M. guilliermondii into fungi-free mice aggravated the features of AHS. M. guilliermondii was found to generate PGE2 by biotransformation of arachidonic acid. Furthermore, the gut fungi (M. guilliermondii)-induced PGE2 production in the liver was confirmed as one of the mechanisms in the chronic AHS. The current study supports the manipulation of the gut microbiota (bacteria and fungi) as an effective and alternative strategy for alleviating ALD.

Keywords: Meyerozyma guilliermondii; Wolfiporia cocos polysaccharides; alcoholic liver diseases; fungi-induced PGE2; gut mycobiota.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1.
Figure 1.
Oral treatment with WIP alleviates chronic ethanol feeding-induced hepatic injury and steatosis
Figure 2.
Figure 2.
WIP treatment ameliorates the ethanol-induced gut dysbiosis
Figure 3.
Figure 3.
Identification of Meyerozyma guilliermondii as a casual fungus for AHS
Figure 4.
Figure 4.
Contribution of fungi-induced PGE2 to alcoholic hepatic steatosis
See this image and copyright information in PMC

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