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Wenxiao ZHAO


Haijun ZHAO


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Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.7 P.650-662


Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency

Author(s):  Wenxiao ZHAO, Chenchen DUAN, Yanli LIU, Guangying LU, Qin LYU, Xiumei LIU, Jun ZHENG, Xuelian ZHAO, Shijun WANG, Haijun ZHAO

Affiliation(s):  School of Nursing, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; more

Corresponding email(s):   zhaowx@sdutcm.edu.cn, haijunzhao@sdutcm.edu.cn

Key Words:  Astragalus polysaccharide, Gut microbiota, Toll-like receptor 4/nuclear factor-κ, B (TLR4/NF-κ, B) pathway, Dampness stagnancy due to spleen deficiency, Immune disorder, Short-chain fatty acid

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Wenxiao ZHAO, Chenchen DUAN, Yanli LIU, Guangying LU, Qin LYU, Xiumei LIU, Jun ZHENG, Xuelian ZHAO, Shijun WANG, Haijun ZHAO. Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency[J]. Journal of Zhejiang University Science B, 2023, 24(7): 650-662.

@article{title="Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency",
author="Wenxiao ZHAO, Chenchen DUAN, Yanli LIU, Guangying LU, Qin LYU, Xiumei LIU, Jun ZHENG, Xuelian ZHAO, Shijun WANG, Haijun ZHAO",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency
%A Wenxiao ZHAO
%A Chenchen DUAN
%A Yanli LIU
%A Guangying LU
%A Qin LYU
%A Xiumei LIU
%A Xuelian ZHAO
%A Shijun WANG
%A Haijun ZHAO
%J Journal of Zhejiang University SCIENCE B
%V 24
%N 7
%P 650-662
%@ 1673-1581
%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200491

T1 - Modulating effects of Astragalus polysaccharide on immune disorders via gut microbiota and the TLR4/NF-κB pathway in rats with syndrome of dampness stagnancy due to spleen deficiency
A1 - Wenxiao ZHAO
A1 - Chenchen DUAN
A1 - Yanli LIU
A1 - Guangying LU
A1 - Qin LYU
A1 - Xiumei LIU
A1 - Jun ZHENG
A1 - Xuelian ZHAO
A1 - Shijun WANG
A1 - Haijun ZHAO
J0 - Journal of Zhejiang University Science B
VL - 24
IS - 7
SP - 650
EP - 662
%@ 1673-1581
Y1 - 2023
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200491

The syndrome of dampness stagnancy due to spleen deficiency (DSSD) is relatively common globally. Although the pathogenesis of DSSD remains unclear, evidence has suggested that the gut microbiota might play a significant role. Radix Astragali, used as both medicine and food, exerts the effects of tonifying spleen and qi. Astragalus polysaccharide (APS) comprises a macromolecule substance extracted from the dried root of Radix Astragali, which has many pharmacological functions. However, whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown. Here, we used DSSD rats induced by high-fat and low-protein (HFLP) diet plus exhaustive swimming, and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes, decreased the levels of interleukin-1β (IL-1β), IL-6, and endotoxin, and suppressed the Toll-like receptor 4/nuclear factor-‍κB (TLR4/NF-‍κb) pathway. Moreover, a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size (LEfSe). APS increased the diversity of the gut microbiota and changed its composition, such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella, and increasing that of Parasutterella, Parabacteroides, Clostridium XIVb, Oscillibacter, Butyricicoccus, and Dorea. APS also elevated the contents of short-chain fatty acids (SCFAs). Furthermore, the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes. In general, our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota, especially for some bacteria involving immune and inflammatory response and SCFA production, as well as the TLR4/NF-κB pathway. This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.


摘要:脾虚水湿不化证亦称为脾虚湿困证,可单独或伴随疾病存在,是一种较为常见的中医证型,尽管其发病机制尚不明确,但有证据表明肠道菌群起着重要作用。黄芪健脾益气,既可药用,又可食用。黄芪多糖(APS)是从黄芪中提取的一种大分子物质,具有多种药理作用。然而,APS能否通过调节肠道菌群改善脾虚水湿不化证机体免疫功能紊乱及相关机制尚未可知。本研究中,我们使用高脂低蛋白饮食结合力竭游泳方法诱导脾虚水湿不化模型大鼠。结果发现,中等分子量的APS增加了模型大鼠的体重和免疫器官指数,降低了IL-1β、IL-6和内毒素水平,并抑制了TLR4/NF-κB通路。此外,LEfSe分析结果显示,共有27个关键菌属被显著富集。APS增加了肠道菌群的多样性,改变了其组成。例如,减少了PseudoflavonifractorParaprevotella的相对丰度,并增加了ParasutterellaParabacteroidesClostridium XIVbOscillibacterButyricicoccusDorea的相对丰度。同时,APS还提高了肠道短链脂肪酸含量。相关分析也表明,12种关键菌属相对丰度与体重增加和免疫器官指数有关。综上所述,APS通过调节脾虚水湿不化大鼠的肠道菌群[特别是涉及免疫和炎症应答、短链脂肪酸(SCFA)产生的菌群]以及TLR4/NF-κB通路,改善了大鼠免疫功能紊乱,为我们深入了解APS治疗脾虚水湿不化证的机制及其作为益生元的潜力提供了实验依据。


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[1]BernardK, 2012. The genus Corynebacterium and other medically relevant coryneform-like bacteria. J Clin Microbiol, 50(10):3152-3158.

[2]YuanB, HanJN, ChengYL, et al., 2020. Identification and characterization of antioxidant and immune-stimulatory polysaccharides in flaxseed hull. Food Chem, 315:126266.

[3]CrovesyL, MastersonD, RosadoEL, 2020. Profile of the gut microbiota of adults with obesity: a systematic review. Eur J Clin Nutr, 74(9):1251-1262.

[4]DahlWJ, Rivero MendozaD, LambertJM, 2020. Chapter eight ‒ diet, nutrients and the microbiome. In: Sun J (Ed.), Progress in Molecular Biology and Translational Science, Vol. 171. Elsevier, the Netherlands, p.237-263.

[5]DevrieseS, EeckhautV, GeirnaertA, et al., 2017. Reduced mucosa-associated Butyricicoccus activity in patients with ulcerative colitis correlates with aberrant claudin-1 expression. J Crohns Colitis, 11(2):229-236.

[6]DuY, WanHT, HuangP, et al., 2022. A critical review of Astragalus polysaccharides: from therapeutic mechanisms to pharmaceutics. Biomed Pharmacother, 147:112654.

[7]DupuitM, ChavanelleV, ChassaingB, et al., 2021. The TOTUM-63 supplement and high-intensity interval training combination limits weight gain, improves glycemic control, and influences the composition of gut mucosa-associated bacteria in rats on a high fat diet. Nutrients, 13(5):1569.

[8]FuJ, WangZH, HuangLF, et al., 2014. Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi). Phytother Res, 28(9):1275-1283.

[9]GoldsteinEJC, TyrrellKL, CitronDM, 2015. Lactobacillus species: taxonomic complexity and controversial susceptibilities. Clin Infect Dis, 60(Suppl 2):S98-S107.

[10]HibberdAA, YdeCC, ZieglerML, et al., 2019. Probiotic or synbiotic alters the gut microbiota and metabolism in a randomised controlled trial of weight management in overweight adults. Benef Microbes, 10(2):121-135.

[11]HongY, LiBB, ZhengNN, et al., 2020. Integrated metagenomic and metabolomic analyses of the effect of Astragalus polysaccharides on alleviating high-fat diet-induced metabolic disorders. Front Pharmacol, 11:833.

[12]JiangYP, QiXH, GaoK, et al., 2016. Relationship between molecular weight, monosaccharide composition and immunobiologic activity of Astragalus polysaccharides. Glycoconj J, 33(5):755-761.

[13]JinML, ZhaoK, HuangQS, et al., 2014. Structural features and biological activities of the polysaccharides from Astragalus membranaceus. Int J Biol Macromol, 64:257-266.

[14]JuTT, KongJY, StothardP, et al., 2019. Defining the role of Parasutterella, a previously uncharacterized member of the core gut microbiota. ISME J, 13(6):1520-1534.

[15]KimJ, ChoiJH, KoG, et al., 2020. Anti-inflammatory properties and gut microbiota modulation of Porphyra tenera extracts in dextran sodium sulfate-induced colitis in mice. Antioxidants, 9(10):988.

[16]KohA, de VadderF, Kovatcheva-DatcharyP, et al., 2016. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell, 165(6):‍1332-1345.

[17]LeiYY, TangL, LiuS, et al., 2021. Parabacteroides produces acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration. Microbiome, 9:115.

[18]LiK, CaoYX, JiaoSM, et al., 2020. Structural characterization and immune activity screening of polysaccharides with different molecular weights from Astragali Radix. Front Pharmacol, 11:582091.

[19]LiMX, GuoCL, WangYQ, et al., 2020. Nostoc sphaeroids Kütz polysaccharide and powder enrich a core bacterial community on C57BL/6j mice. Int J Biol Macromol, 162:1734-1742.

[20]LiY, QinGYX, ChengC, et al., 2020. Purification, characterization and anti-tumor activities of polysaccharides from Ecklonia kurome obtained by three different extraction methods. Int J Biol Macromol, 150:1000-1010.

[21]LiuJ, QiaoB, TanZJ, 2022. Progress in modern research on substance of spleen qi deficiency in Chinese medicine. World Chin J Digestol, 30(16):693-700 (in Chinese).

[22]LouisP, FlintHJ, 2009. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett, 294(1):1-8.

[23]LouisS, TappuRM, Damms-MachadoA, et al., 2016. Characterization of the gut microbial community of obese patients following a weight-loss intervention using whole metagenome shotgun sequencing. PLoS ONE, 11(2):e0149564.

[24]LuYT, LiuHY, YangK, et al., 2022. A comprehensive update: gastrointestinal microflora, gastric cancer and gastric premalignant condition, and intervention by traditional Chinese medicine. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(1):1-18.

[25]MassierL, ChakarounR, TabeiS, et al., 2020. Adipose tissue derived bacteria are associated with inflammation in obesity and type 2 diabetes. Gut, 69(10):1796-1806.

[26]MessaoudeneM, PidgeonR, RichardC, et al., 2022. A natural polyphenol exerts antitumor activity and circumvents anti-PD-1 resistance through effects on the gut microbiota. Cancer Discov, 12(4):1070-1087.

[27]MingK, ZhuangS, MaN, et al., 2022. Astragalus polysaccharides alleviates lipopolysaccharides-induced inflammatory lung injury by altering intestinal microbiota in mice. Front Microbiol, 13:1033875.

[28]OddiS, HuberP, Rocha Faria DuqueAL, et al., 2020. Breast-milk derived potential probiotics as strategy for the management of childhood obesity. Food Res Int, 137:109673.

[29]PaharikAE, HorswillAR, 2016. The staphylococcal biofilm: adhesins, regulation, and host response. Microbiol Spectr, 4(2):VMBF-0022-2015.

[30]Parada VenegasD, de la FuenteMK, LandskronG, et al., 2019. Short chain fatty acids (SCFAs)‍-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol, 10:277.

[31]PutignaniL, OlivaS, IsoldiS, et al., 2021. Fecal and mucosal microbiota profiling in pediatric inflammatory bowel diseases. Eur J Gastroenterol Hepatol, 33(11):1376-1386.

[32]SakamotoM, TakagakiA, MatsumotoK, et al., 2009. Butyricimonas synergistica gen. nov., sp. nov. and Butyricimonas virosa sp. nov., butyric acid-producing bacteria in the family ‘Porphyromonadaceae’ isolated from rat faeces. Int J Syst Evol Microbiol, 59(7):1748-1753.

[33]ShangHX, SunJ, ChenYQ, 2016. Clostridium butyricum CGMCC0313.1 modulates lipid profile, insulin resistance and colon homeostasis in obese mice. PLoS ONE, 11(4):e0154373.

[34]ShengZL, LiuJM, YangB, 2021. Structure differences of water soluble polysaccharides in Astragalus membranaceus induced by origin and their bioactivity. Foods, 10(8):1755.

[35]SongBC, LiP, YanSJ, et al., 2022. Effects of dietary astragalus polysaccharide supplementation on the Th17/Treg balance and the gut microbiota of broiler chickens challenged with necrotic enteritis. Front Immunol, 13:781934.

[36]SongQB, ChengSW, LiD, et al., 2022. Gut microbiota mediated hypoglycemic effect of Astragalus membranaceus polysaccharides in db/db mice. Front Pharmacol, 13:1043527.

[37]Tamanai-ShacooriZ, SmidaI, BousarghinL, et al., 2017. Roseburia spp.: a marker of health? Future Microbiol, 12(2):157-170.

[38]ThaissCA, ZmoraN, LevyM, et al., 2016. The microbiome and innate immunity. Nature, 535(7610):65-74.

[39]TurnbaughPJ, LeyRE, MahowaldMA, et al., 2006. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122):1027-1031.

[40]UbedaC, BucciV, CaballeroS, et al., 2013. Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization. Infect Immun, 81(3):965-973.

[41]WangK, LiaoMF, ZhouN, et al., 2019. Parabacteroides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids. Cell Rep, 26(1):222-235.e5.

[42]WeiXY, TaoJH, XiaoSW, et al., 2018. Xiexin Tang improves the symptom of type 2 diabetic rats by modulation of the gut microbiota. Sci Rep, 8:3685.

[43]WeissGA, ChassardC, HennetT, 2014. Selective proliferation of intestinal Barnesiella under fucosyllactose supplementation in mice. Br J Nutr, 111(9):1602-1610.

[44]WuMN, LiPZ, AnYY, et al., 2019. Phloretin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice by regulating the gut microbiota. Pharmacol Res, 150:104489.

[45]WuTR, LinCS, ChangCJ, et al., 2019. Gut commensal Parabacteroides goldsteinii plays a predominant role in the anti-obesity effects of polysaccharides isolated from Hirsutella sinensis. Gut, 68(2):248-262.

[46]WuX, XuNN, YeZQ, et al., 2022. Polysaccharide from Scutellaria barbata D. Don attenuates inflammatory response and microbial dysbiosis in ulcerative colitis mice. Int J Biol Macromol, 206:1-9.

[47]YangXY, JiaCH, 2013. Understanding association of spleen system with earth on traditional Chinese medicine theory. J Tradit Chin Med, 33(1):134-136.

[48]YuanX, ChenRM, McCormickKL, et al., 2021. The role of the gut microbiota on the metabolic status of obese children. Microb Cell Fact, 20:53.

[49]ZaidiSJ, HusayniT, CollinsMA, 2018. Gemella bergeri infective endocarditis: a case report and brief review of literature. Cardiol Young, 28(5):762-764.

[50]ZhangL, DuJF, YanoN, et al., 2017. Sodium butyrate protects against high fat diet induced cardiac dysfunction and metabolic disorders in type II diabetic mice. J Cell Biochem, 118(8):2395-2408.

[51]ZhaoWX, CuiN, JiangHQ, et al., 2017. Effects of radix astragali and its split components on gene expression profiles related to water metabolism in rats with the dampness stagnancy due to spleen deficiency syndrome. Evid Based Complement Alternat Med, 2017:4946031.

[52]ZhaoWX, ChenLJ, CuiN, et al., 2019. Polysaccharides from radix astragali exert immunostimulatory effects to attenuate the dampness stagnancy due to spleen deficiency syndrome. Pharmacogn Mag, 15(63):500-506.

[53]ZhaoWX, WangT, ZhangYN, et al., 2022. Molecular mechanism of polysaccharides extracted from Chinese medicine targeting gut microbiota for promoting health. Chin J Integr Med, in press.

[54]ZhongMY, YanY, YuanHS, et al., 2022. Astragalus mongholicus polysaccharides ameliorate hepatic lipid accumulation and inflammation as well as modulate gut microbiota in NAFLD rats. Food Funct, 13(13):7287-7301.

[55]ZhouLJ, LiuZJ, WangZX, et al., 2017. Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo. Sci Rep, 7:44822.

[56]ZhuLL, ShaLP, LiK, et al., 2020. Dietary flaxseed oil rich in omega-3 suppresses severity of type 2 diabetes mellitus via anti-inflammation and modulating gut microbiota in rats. Lipids Health Dis, 19:20.

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