Elsevier

Food Bioscience

Volume 47, June 2022, 101426
Food Bioscience

Auricularia polytricha and Flammulina velutipes ameliorate inflammation and modulate the gut microbiota via regulation of NF-κB and Keap1/Nrf2 signaling pathways on DSS-induced inflammatory bowel disease

https://doi.org/10.1016/j.fbio.2021.101426Get rights and content

Highlights

  • The main bioactive molecules were collected from A. polytricha and F. velutipes.

  • APE and FVE attenuated clinical factors and regulated inflammatory cytokines.

  • APE and FVE inhibited NF-κB and MAPK/ERK as well as stimulated Keap1/nrf2 signaling pathways.

  • APE and FVE modulated the gut microbiota via increasing SCFAs contents.

Abstract

Flammulina velutipes and Auricularia polytricha are two popular dietary mushrooms, especially in the Northeast of China. They have revealed many pharmacological effects due to their bioactive compounds, but their possible mechanism of action involved in inflammation remains poorly known. Therefore, Inflammatory bowel disease (IBD) which is a chronic disease and progressive inflammation in the gastrointestinal tract were used to evaluate their anti-inflammatory and modulatory properties on the intestinal microbiota via the signaling pathways involved by oral administration of F. velutipes (FVE) and A. polytricha (APE). Mice were daily received 3%DSS in the drinking water followed by the daily administration of FVE and APE. The food consumption, weight variation and DAI score were assessed during the experiment and inflammatory parameters, mRNA and protein expressions to determine the possible signaling pathways involved, and the gut microbiota from the cecum by high-throughput sequencing. Data showed that APE and FVE improved clinical symptoms, inflammatory cytokines and oxidative markers. They also attenuated the mRNA and proteins expressions in colon tissue. Moreover, APE and FVE regulated DSS-induced intestinal dysbiosis and stimulated the SCFAs production. Overall, APE and FVE could improve DSS-induced IBD in mice suggesting that they represent novels therapeutic drugs and could be used as prebiotic to modulate the gut microbiota and preserve intestinal integrity.

Introduction

During the last 15 years, studies have been multiplied to better understand the microbes, mainly bacteria, that generally resides in the colon of a healthy human. Although these investigations began in the late twentieth century, the considerable progress made in the methodologies of innovative techniques such as sequencing or bioinformatics has allowed acquiring a more in-depth knowledge of microbes living in the gastrointestinal ecosystem (Franzosa et al., 2015). Hence the term "gut microbiota" is generally used, and it denotes the bacterial community that resides in the intestine and plays an important role in host defense via colonization resistance and encouraging the development and regulation of acquired mucosal immune system (Qin et al., 2010; Round & Mazmanian, 2009). It forms a unique metagenome, is dynamic and changes with person's nutritional status, geography and age (Hooper et al., 2012). However, some inflammatory diseases could be triggered through the modifications made in the ecosystem, which can impact the intestinal microbiota and thus induce an imbalanced microbiota. It is the case of colitis characterized by a transition in the intestinal microbiome, which goes from an "eubiotic" state to a "dysbiotic" state, with interesting therapeutic implications (Sethi et al., 2018).

The IBD pathogenesis remains uncertain, even though many environmental and physiological factors have been associated with the development of pathogens. This intestinal dysbiosis is thought to be closely related to gastrointestinal disease (Kostic et al., 2014; Mar et al., 2014). The intestinal microbiota is known as a big community of bacteria that colonizes the intestine with effective metabolic actions for different enzymes and other functions such as proliferation/differentiation of intestinal epithelial cells, barrier function and intestinal development affecting the physiology and pathology of the mucosal immune system of the host (Qin et al., 2010). At the beginning of the 21st century, IBD has become a global disease with a growing effect in newly industrialized countries like China with a prevalence exceeding 0.3%, highlighting the importance of preventing and innovating health systems to manage this disease (Ng et al., 2020). Many researches have thus multiplied to find alternative solutions to conventional treatments such as antibiotics that often tend to treat the consequences but not the cause of the problem.

Recent discoveries suggest effective strategies for disease management by going directly through the improvement of the gut microbiota often considered the source of the problem. Among the alternative therapeutic substances used clinically to treat dysbiosis and thus treat pathologies, prebiotics are shown to be effective (Gibson et al., 2017). These are chemical compounds, particularly those related to dietary fiber like oligosaccharides, which serve as a source of energy for the bacteria during their passage in the intestinal tract and stimulate the proliferation and the activity of some bacteria in the intestine. Previous studies revealed that polysaccharides of plants and even animals constitute a considerable proportion of bioactive compounds for the prebiotic's development (Li et al., 2013; Shang et al., 2018a, 2018b; Shi et al., 2016; Tao et al., 2017). Flammulina velutipes and Auricularia polytricha are two edible mushrooms very coveted in the daily diet, especially in North-Eastern China during winter due to their delicious taste, nutritional value and above all their medicinal properties. These properties are mainly due to their active molecules, such as polysaccharides which have already been the subject of several studies, and exhibiting varied beneficial effects (Chellappan et al., 2016; Chu et al., 2017; Shah et al., 2018; Wu et al., 2014; Yu et al., 2014; Zhao et al., 2016). Thus, to deepen the knowledge on these mushrooms, this study aimed to assess the beneficial effects of the crude extracts of Flammulina velutipes (FVE) and Auricularia polytricha (APE) and the potential signaling pathways involved in the intestinal microbiota by DSS-induced ulcerative colitis.

Section snippets

Chemicals and reagents

5-aminosalicylic acid was purchased from Shanghai Ethypharm Pharmaceuticals Co. Ltd. (Shanghai, China). DSS was purchased from Yuanye Bio. (Shanghai, China). ELISA kits were purchased from Jiangsu Jingmei Biological Technology Co. Ltd. (Nanjing, Jiangsu, China). NO biochemical assay kit was purchased from Elabscience (Elabscience Biotechnology Co. Ltd. Wuhan, Hubei, China). MPO assay kit was purchased from Nanjing Jiancheng Bioengineering Institute (Nanjing, Jiangsu, China). TriZol, reverse

Chemical analysis of APE and FVE and antioxidant properties

Table S4 described the bioactive compounds present in APE and FVE revealing the presence of flavonoids, alkaloids, saponins, steroids, terpenoids, glycosides, tannins and phenolics. The quantification of the constituent oses showed that the concentration of sugars (total oses, neutral oses and uronic acids mainly) were significantly higher in APE than in FVE, while the level of reducing sugars was substantially equal (Table S5) but the flavonoids levels were higher in FVE than in APE (Fig. S1A

Discussion

The intestinal microbiota plays a crucial role in the health of the human body owing to its ecosystem known to be dense and diverse. So, any disruption of its microflora could be associated with intestinal pathologies (Qin et al., 2010). The main causes as well as the signaling pathways involved in these diseases, mainly ulcerative colitis, remain largely unclear. But their manifestations involve colon inflammation accompanied by diarrhea, body weight loss, and an imbalance of the intestinal

Conclusion

In view of the effectiveness of the Flammulina velutipes polysaccharides recognized due to many previous studies as well as their extensive use in dietary formulation, the beneficial effects of crude extracts, in addition to another very consumed mushrooms Auricularia polytricha, have been studied to highlight the other bioactive molecules they could contain. According to the DSS-induced ulcerative colitis model, APE and FVE administration could ameliorate inflammatory and antioxidant

Declaration of competing interest

There has no conflict of interest to declare.

Acknowledgements:

The authors wish to express sincere gratitude to undergraduate students especially Han Songbo and Yue Zixiang for their unconditional help during the experiment and data analysis and grateful the School of Life Science, Jilin Agricultural University for providing chemicals to realize this experiment.

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