Tremella fuciformis polysaccharide reduces obesity in high-fat diet-fed mice by modulation of gut microbiota

Abstract

Obesity is a metabolic disease associated with gut microbiota and low-grade chronic inflammation. Tremella fuciformis is a medicinal and edible fungus; polysaccharide (TP) is the main active component, which has a variety of biological activities, such as hypoglycemic and hypolipidemic. However, the anti-obesity effects and potential mechanisms of TP have never been reported. This study was conducted to elucidate the inhibitory effect of TP on high-fat diet (HFD)-induced obesity in mice. Mice were split into five groups: normal chow diet (NCD) group, NCD_TP_H group, HFD group, HFD_TP_L group and HFD_TP_H group. Our study showed that TP inhibited high-fat diet-induced weight gain and fat accumulation in mice and reduced blood glucose, hyperlipidemia and inflammation. TP also improved gut microbiota disorders by reducing the Firmicutes/Bacteroidetes ratio and modulating the relative abundance of specific gut microbiota. We also found that the anti-obesity and gut microbiota-modulating effects of TP could be transferred to HFD-fed mice via faecal microbiota transplantation (FMT), confirming that the gut microbiota was one of the targets of TP for obesity inhibition. Further studies showed that TP increased the production of short-chain fatty acids and the secretion of intestinal hormones. Our studies showed that TP inhibited obesity by modulating inflammation and the microbe-gut-brain axis, providing a rationale for developing TP to treat obesity and its complications.

Keywords: SCFAs; Tremella fuciformis polysaccharide; gut microbiota; inflammation; microbe-gut-brain axis; obesity.

Figure 1

Characterise of TP, (A) UV–VIS absorption spectra, (B) High-performance size exclusion chromatograms, (C) HPLC analysis of monosaccharide composition, (D) FT-IR spectra.

Figure 2

TP attenuated fat accumulation and hyperlipidemia in HFD-fed mice. (A) Body weight gain. (B) Epididymal fat and perirenal fat weight. (C) Weight of different organs. (D) Morphological observations of the epididymis fat. (E) Haematoxylin and eosin staining of epididymis fat. (F) Epididymal adipocyte size. (G) Fasting glucose. (H) Oral glucose tolerance test. (I) AUC of OGTT. Data were shown as means ± SD (n = 6). Statistical analysis was performed using one-way ANOVA; ns for p > 0.05; *p < 0.05; **p < 0.01; ***p < 0.001; and ****P < 0.0001.

Figure 3

TP modulated the diversity of the gut microbiota. Beta diversity of faecal microbiota of the five groups, including (A) principal components analysis (PCoA) plot and non-metric multidimensional scaling (NMDS) analysis. (B) Alpha Diversity-related boxplot analysis, including (C) chao1, (D) observed species, (E) shannon and (F) simpson index. Data were shown as means ± SD (n = 6). Statistical analysis was performed using one-way ANOVA; ns for p > 0.05; *p < 0.05; **p < 0.01; ***p < 0.001; and ****p < 0.0001.

Figure 4

TP modulated the composition of the gut microbiota. (A) Phylum-, (E) family-, and (I) genus-level distribution of faecal microbiota. (B,C) Relative abundance of the phyla Bacteroidota and Firmicutes; (D) the ratio between the relative abundance of Firmicutes and Bacteroidota. (F-H,J-L) relative abundance of identified differential abundant bacterial groups at family- and genus-level. Data were shown as means ± SD (n = 6). Statistical analysis was performed using one-way ANOVA; ns for p > 0.05; *p < 0.05; **p < 0.01; ***p < 0.001; and ****p < 0.0001.

Figure 5

TP regulated the expression of related genes and proteins. Relative expression of (A) FFAR2, (B) GLP-1, and (C) PYY in the colon compared to the NCD group; relative expression of (D) NPY, (E) AGRP, (F) CART, and (G) POMC in the hypothalamus compared to the normal group. Protein expression of (H) GLP-1R, POMC and (I) NPY2R, AgRP in the hypothalamus. Data were shown as means ± SD (n = 6). Statistical analysis was performed using one-way ANOVA; ns for p > 0.05; *p < 0.05; **p < 0.01; ***p < 0.001; and ****p < 0.0001.

Figure 6

Faecal microbiota transplantation attenuated fat accumulation in HFD-fed mice. The four groups of recipient mice (fed high-fat chow) that received faecal transplants were designated as NCD_HFD, NCD_H_HFD, HFD_HFD and HFD _H_HFD, respectively. (A) Body weight gain. (B) Epididymal fat and perirenal fat weight. (C) Weight of different organs. (D) Morphological observations of the epididymis fat. (E) Haematoxylin and eosin staining of epididymis fat. (F) Epididymal adipocyte size. Data were shown as means ± SD (n = 6). Statistical analysis was performed using one-way ANOVA; ns for p > 0.05; *p < 0.05; **p < 0.01; ***p < 0.001; and ****p < 0.0001.

Figure 7

Faecal microbiota transplantation modulated the diversity of the gut microbiota. Faecal transplantation from NCD-, NCD_TP_H-, HFD-, and HFD_TP_H-fed mice was performed, and relevant microbiota analysis was conducted. Beta diversity of faecal microbiota of the four groups, including (A) principal components analysis (PCoA) plot, non-metric multidimensional scaling (NMDS) analysis (B) and hierarchical clustering (C). Alpha Diversity-related boxplot analysis, including ACE (D), chao 1 (E), observed-species (F), shannon (G) and simpson index (H). Data were shown as means ± SD (n = 6). Statistical analysis was performed using one-way ANOVA; ns for p > 0.05; *p < 0.05; **P < 0 0.01; and ***p < 0.001.

Figure 8

Faecal microbiota transplantation modulated the composition of the gut microbiota. (A) Phylum-, (E) family-, and (I) genus-level distribution of faecal microbiota. (B,C) relative abundance of the phyla Bacteroidota and Firmicutes; (D) the ratio between the relative abundance of Firmicutes and Bacteroidota. (F-H,J-L) relative abundance of identified differential abundant bacterial groups at family- and genus-level. Data were shown as means ± SD (n = 6).Statistical analysis was performed using one-way ANOVA; ns for p > 0.05; *p < 0.05; **p < 0.01; and ***p < 0.001.

Figure 9

Proposed mechanisms underlying the inhibitory effects of TP on HFD-induced obesity and inflammation.