Effects of Polysaccharides From Auricularia auricula on the Immuno-Stimulatory Activity and Gut Microbiota in Immunosuppressed Mice Induced by Cyclophosphamide.

Xianghui Kong,Zhenhua Duan,Weiwen Duan,Dingjin Li,Xiaoxian Tang

doi:10.3389/fimmu.2020.595700

Xianghui Kong, Zhenhua Duan + Show 3 more

Open Access

https://doi.org/10.3389/fimmu.2020.595700

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Abstract

Recently, the immuno-enhancing potential of polysaccharide from Auricularia auricula (AAP) has been an area of research interest. However, the immune-stimulatory activity and mechanisms of AAP in immunosuppressive mice treated with cyclophosphamide (CTX) are still poorly understood. This study aimed to evaluate the immuno-enhancing effects of AAP and mine its possible mechanisms. Firstly, polysaccharides were isolated from A. auricula and purified. Secondly, the immune-stimulatory activities of the first AAP fraction (AAP1) were evaluated in the CTX-treated mice. Results showed that AAP1 significantly enhanced immune organ indexes, remarkably stimulated IFN-γ, IL-2, IL-4, IL-10, and TNF-α levels in the serum, and dramatically up-regulated the mRNA levels of Claudin-1, Occludin and ZO-1. Compared to the CTX group, AAP1 administration restored the gut microbiota composition similar to that of the control group by decreasing the ratio of Firmicutes/Bacteroidetes and increasing the relative abundances of short-chain fatty acid-producing microbiota. This study provides useful information for its further application as an immune-stimulator in foods and drugs.

Highlights

Chemotherapy is widely recognized as a therapeutic procedure for treating tumor growth [1]
The crude polysaccharide isolated from A. auricular was first purified by an anion-exchange chromatography of DEAE-52 column, and four fractions (AAP1, AAP2, AAP3, and AAP4) were obtained (Figure 1A)
Compared with the CTX group, AAP1 increased the contents of acetate, propionate and butyrate in CTX-treated mice. These findings indicated that AAP1 could enhance short-chain fatty acids (SCFAs) production, which is in accordance with the increased abundances of SCFAs-producing microbiota

Summary

Introduction

Chemotherapy is widely recognized as a therapeutic procedure for treating tumor growth [1] Among the agents, it often involves the use of cyclophosphamide (CTX), reputed for treating a variety of cancers and autoimmune disorders [2,3,4]. Accumulating evidence support the postulation that the complex gut ecosystem has a strong relationship with the proper development of the host immune system [8, 9]. The latter, aside from ensuring the detection and removal of harmful organisms, prevents the dysbiosis of the gut microbiota, suggesting a complex beneficial interaction. Imbalances in the gut microbiota have been implicated in many immune and immune-related disorders [10]

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