Herbal medicine in the treatment of COVID-19 based on the gut-lung axis

Abstract

Respiratory symptoms are most commonly experienced by patients in the early stages of novel coronavirus disease 2019 (COVID-19). However, with a better understanding of COVID-19, gastrointestinal symptoms such as diarrhea, nausea, and vomiting have attracted increasing attention. The gastrointestinal tract may be a target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The intestinal microecological balance is a crucial factor for homeostasis, including immunity and inflammation, which are closely related to COVID-19. Herbal medicine can restore intestinal function and regulate the gut flora structure. Herbal medicine has a long history of treating lung diseases from the perspective of the intestine, which is called the gut-lung axis. The physiological activities of guts and lungs influence each other through intestinal flora, microflora metabolites, and mucosal immunity. Microecological modulators are included in the diagnosis and treatment protocols for COVID-19. In this review, we demonstrate the relationship between COVID-19 and the gut, gut-lung axis, and the role of herbal medicine in treating respiratory diseases originating from the intestinal tract. It is expected that the significance of herbal medicine in treating respiratory diseases from the perspective of the intestinal tract could lead to new ideas and methods for treatment.

Keywords

COVID-19 / Gut-lung axis / Gut microbiota / Herbal medicine / Respiratory disease / SARS-CoV-2

References

[[1]] Davis EL, Lucas TCD, Borlase A, et al.Contact tracing is an imperfect tool for controlling COVID-19 transmission and relies on population adherence. Nat Commun. 2021;12(1):5412.

[[2]] Li Q, Guan XH, Wu P, et al.Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl [J] Med. 2020;382(13):1199-1207.

[[3]] Munster VJ, Koopmans M, van Doremalen N, et al. A novel coronavirus emerging in China-key questions for impact assessment. N Engl [J] Med. 2020;382(8):692-694.

[[4]] Zhu N, Zhang D, Wang W, et al.A novel coronavirus from patients with pneumonia in China. N Engl [J] Med. 2020;382(8):727-733.

[[5]] Mittal A, Manjunath K, Ranjan RK, et al.COVID-19 pandemic: insights into structure, function, and hACE2 receptor recognition by SARS-CoV-2. PLoS Pathog. 2020;16(8):e1008762.

[[6]] Andersen KG, Rambaut A, Lipkin WL, et al.The proximal origin of SARS-CoV-2. Nat Med. 2020;26(4):450-452.

[[7]] Chan JF, Kok KH, Zhu Z, et al.Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020;9(1):221-236.

[[8]] World Health Organization (WHO). Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. Available from: https://www.who.int/csr/sars/country/table2004_04_21/en/.

[[9]] World Health Organization (WHO). Coronavirus disease 2019 (COVID-19) situation report-52. Available from: https://www.who.int/docs/default-source/coronaviruse/20200312-sitrep-52-covid-19.pdf?sfvrsn=e2bfc9c0_2.

[[10]] Lamers MM, Beumer J, Vaart JVD, et al.SARS-CoV-2 productively infects human gut enterocytes. Science. 2020;369(6499):50-54.

[[11]] Cholankeril G, Podboy A, Aivaliotis VL, et al.High prevalence of concurrent gastrointestinal manifestations in patients with severe acute respiratory syndrome coronavirus 2: early experience from California. Gastroenterology. 2020;159(2):775-777.

[[12]] Guan WJ, Ni ZY, Hu Y, et al.Clinical characteristics of coronavirus disease 2019 in China. N Engl [J] Med. 2020;382(18):1708-1720.

[[13]] Dousari AS, Moghadam MT, Satarzadeh N. COVID-19 (coronavirus disease 2019): a new coronavirus disease. Infect Drug Resist. 2020;13:2819-2828.

[[14]] Zhou ZL, Zhao N, Shu Y, et al.Effect of gastrointestinal symptons in patients with COVID-19. Gastroenterology. 2020;158(8):2294-2297.

[[15]] Qian Q, Fan LF, Liu WC, et al.Direct evidence of active SARS-CoV-2 replication in the intestine. Clin Infect Dis. 2021;73(3):361-366.

[[16]] Du ML, Cai GS, Chen F, et al.Multiomics evaluation of gastrointestinal and other clinical characteristics of COVID-19. Gastroenterology. 2020;158(8):2298-2301.

[[17]] Zhang JC, Xie B, Hashimoto K.Current status of potential therapeutic candidates for the COVID-19 crisis. Brain Behav Immun. 2020;87:59-73.

[[18]] The National Health Commission of the People’s Republic of China, The State Administration of TCM. Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (eighthed. trial version). Available from: http://www.nhc.gov.cn/yzygj/s7653p/202008/0a7bdf12bd4b46e5bd28ca7f9a7f5e5a.shtml.

[[19]] Kim HS.Do an altered gut microbiota and an associated leaky gut affect COVID-19 severity? mBio. 2021;12(1):e03022-e03020.

[[20]] Tang LL, Gu S, Gong YW, et al.Clinical significance of the correlation between changes in the major intestinal Bacteria Species and COVID-19 Severity. Engineering. 2020;6(10):1178-1184.

[[21]] Lavelle A, Sokol H.Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020;17(4):223-237.

[[22]] Wang JJ, Qi FH.Traditional Chinese medicine to treat COVID-19: the importance of evidence-based research. Drug Discov Ther. 2020;14(3):149-150.

[[23]] Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology. 2020;159(3):944-955.e8.

[[24]] Gheblawi M, Wang KM, Viveiros A, et al.Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2. Circ Res. 2020;126(10):1456-1474.

[[25]] Xiao F, Tang MW, Zheng XB, et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020;158(6):1831-1833.

[[26]] Hashimoto T, Perlot T, Rehman A, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 2012;487(7408):477-481.

[[27]] Geva-Zztorsky N, Sefik E, Kua L, et al. Mining the human gut microbiota for immunomodulatory organisms. Cell. 2017;168(5):928-943.

[[28]] Yang T, Chakraborty S, Saha P, et al.Gnotobiotic rats reveal that gut microbiota regulates colonic mRNA of ACE2, the receptor for SARS-CoV-2 infectivity. Hypertension. 2020;76(1):e1-e3.

[[29]] d’Ettorre G, Ceccarella G, Marazzato M, et al. Challenges in the management of SAR-CoV2 infection: the role of oral bacteriotherapy as complementary therapeutic strategy to avoid the progression of COVID-19. Front Med (Lausanne). 2020;7:389.

[[30]] Wu LH, Ye ZN, Ping P, et al. Efficacy and safety of washed microbiota transplantation to treat patients with mild-to-severe COVID-19 and suspected of having gut microbiota dysbiosis: study protocol for a randomized controlled trial. Curr Med Sci. 2021;41(6):1087-1095.

[[31]] Oliveira GLV, Oliveira CNS, Pinzan CF, et al. Microbiota modulation of the gut-lung axis in COVID-19. Front Immunol. 2021;12:635471.

[[32]] Ivashkin V, Fomin V, Moiseev S, et al.Efficacy of a probiotic consisting of Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301 in the treatment of hospitalized patients with COVID-19: a randomized controlled trial. Probiotics Antimicrob Proteins. 2021;13:1-9.

[[33]] Fujimura KE, Sitarik AR, Havstad S, et al.Neonatal gut microbiota associates with childhood multisensitized atopy and T cell differentiation. Nat Med. 2016;22(10):1187-1191.

[[34]] Hanada S, Pirzadeh M, Carver KY, et al.Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia. Front Immunol. 2018;9:2640.

[[35]] Wang DW, Hu B, Hu C, et al.Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069.

[[36]] Belkaid Y, Hang TW.Role of the microbiota in immunity and inflammation. Cell. 2014;157(1):121-141.

[[37]] Kalantar-Zadeh K, Ward SA, Kalantar-Zadeh K, et al. Considering the effects of microbiome and diet on SARS-CoV-2 infection: nanotechnology roles. ACS Nano. 2020;14(5):5179-5182.

[[38]] Mak JWY, Chan FKL, Ng SC.Probiotics and COVID-19: one size does not fit all. Lancet Gastroenterol Hepatol. 2020;5(7):644-645.

[[39]] Hu JL, Zhang L, Lin W, et al.Review article: probiotics, prebiotics and dietary approaches during COVID-19 pandemic. Trends Food Sci Technol. 2021;108:187-196.

[[40]] Biliński J, Winter K, Jasiński M, et al.Rapid resolution of COVID-19 after faecal microbiota transplantation. Gut. 2022;71(1):230-232.

[[41]] Enaud R, Prevel R, Ciarlo E, et al.The gut-lung axis in health and respiratory diseases: a place for inter-organ and inter-kingdom crosstalks. Front Cell Infect Microbiol. 2020;10:9.

[[42]] Kao H, F, Wang YC, Tseng HY, et al. Goat milk consumption enhances innate and adaptive immunities and alleviates allergen-induced airway inflammation in offspring mice. Front Immunol. 2020;11(18):184.

[[43]] Barcik W, Boutin RCT, Sokolowska M, et al.The role of lung and gut microbiota in the pathology of asthma. Immunity. 2020;52(2):241-255.

[[44]] Chakradhar SA.Curious connection: teasing apart the link between gut microbes and lung disease. Nat Med. 2017;23(4):402-404.

[[45]] Kumai M, Coria AL, Cornick S, et al.Increased intestinal permeability exacerbates sepsis through reduced hepatic SCD-1activity and dysregulated iron recycling. Nat Commun. 2020;11(1):483.

[[46]] Tomita Y, Ikeda T, Sakata S, et al.Association of probiotic Clostridium butyricum therapy with survival and response to immune checkpoint blockade in patients with lung cancer. Cancer Immunol Res. 2020;8(10):1236-1242.

[[47]] Groves HT, Higham SL, Moffatt MF, et al.Respiratory viral infection alters the gut microbiota by inducingInappetence. mBio. 2020;11(1):e03236-e03219.

[[48]] Dhar D, Mohanty A.Gut microbiota and COVID-19-possible link and implications. Virus Res. 2020;285:198018.

[[49]] Lelie Dvd TS.COVID-19 and the gut microbiome: more than a gut feeling. mSystems. 2020;5(4):E00453-E00420.

[[50]] Koh A, Vadder FD, Kovatcheva-Datchary P, et al. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016;165(6):1332-1345.

[[51]] Theiler A, Bärnthaler T, Platzer W, et al.Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival. [J] Allergy Clin Immunol. 2019;144(3):764-776.

[[52]] Antunes KH, Fachi JL, d PR, et al. Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response. Nat Commun. 2019;10(1):3273.

[[53]] Arpaia N, Campbell C, Fan XY, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451-455.

[[54]] Steed AL, Christophi GP, Kaiko GE, et al. The microbial metabolite desaminotyrosine protects from influenza through type I interferon[J]. Science. 2017;357(6350):498-502.

[[55]] Tulic MK, Piche T, Verhasselt V, et al.Lung-gut cross-talk: evidence, mechanisms and implications for the mucosal inflammatory diseases. Clin Exp Allergy. 2016;46(4):519-528.

[[56]] Samuelson DR, Welsh DA, Shellito JE.Regulation of lung immunity and host defense by the intestinal microbiota. Front Microbiol. 2015;6:1085.

[[57]] Mjösberg J, Rao A.Lung inflammation originating in the gut. Science. 2018;359(6371):36-37.

[[58]] Huang YF, Mao KR, Chen X, et al.S₁P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense. Science. 2018;359(6371):114-119.

[[59]] Miao J, Yang X, Yan YF, et al.Experiment and clinical research of “Exterion and Interior of the Lung and Large Intestine”. Liaoning [J] Tradit Chin Med. 2017;19(12):183-185.

[[60]] Xia XT, Wen MY, Zhan SF, et al.Treatment to COVID-19 based on theory of simultaneous treatment to lung and large intestine: a preliminary clinical trial. Liaoning [J] Tradit Chin Med. 2021;48(10):35-37.

[[61]] Zhang WJ, Dai Y.Research advances of lung-gut axis. [J] Pharm Res. 2022;41(1):53-56.

[[62]] Zhang Q, Yue SJ, Wang WX, et al.Potential role of gut microbiota in traditional Chinese medicine against COVID-19. Am [J] Chin Med. 2021;49(4):785-803.

[[63]] Lu HR, Zhang LX, Xiao JF, et al. Effect of feeding Chinese herb medicine ageratum-liquid on intestinal bacterial translocations induced by H9N2 AIV in mice. Virol J. 2019;16(1):24.

[[64]] Wang J, Ishfaq M, Li J.Baicalin ameliorates mycoplasma gallisepticum-induced inflammatory injury in the chicken lung through regulating the intestinal microbiota and phenylalanine metabolism. Food Funct. 2021;12(9):4092-4104.

[[65]] Chen QH, Liu JJ, Wang WQ, et al. Sini decoction ameliorates sepsis-induced acute lung injury via regulating ACE2-Ang (1-7)-Mas axis and inhibiting the MAPK signaling pathway. Biomed Pharmacother. 2019;115:108971.

[[66]] Ho TY, Wu SL, Chen JC, et al.Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res. 2007;74(2):92-101.

[[67]] Deng L, Shi YC, Liu P, et al.GeGen QinLian decoction alleviate influenza virus infectious pneumonia through intestinal flora. Biomed Pharmacother. 2021;141:111896.

[[68]] Wang YA, Li N, Li QY, et al. Xuanbai Chengqi decoction ameliorates pulmonary inflammation via reshaping gut microbiota and rectifying Th17/Treg imbalance in a murine model of chronic obstructive pulmonary disease. Int [J] Chron Obstruct Pulmon Dis. 2021;16:3317-3335.

[[69]] Tsang MSM, Cheng SW, Zhu J, et al.Anti-inflammatory activities of pentaherbs formula and its influence on gut microbiota in allergic asthma. Molecules. 2018;23(11):2776.

[[70]] Shi NN, Liu B, Liang N, et al. Association between early treatment with Qingfei Paidu decoction and favorable clinical outcomes in patients with COVID-19: a retrospective multicenter cohort study. Pharmacol Res. 2020;161:105290.

[[71]] Zhang LH, Zheng X, Bai XK, et al.Association between use of Qingfei Paidu Tang and mortality in hospitalized patients with COVID-19: a national retrospective registry study. Phytomedicine. 2021;85:153531.

[[72]] Xin SY, Cheng XQ, Zhu B, et al.Clinical retrospective study on the efficacy of Qingfei Paidu decoction combined with Western medicine for COVID-19 treatment. Biomed Pharmacother. 2020;129:110500.

[[73]] Zong XY, Liang N, Wang JY, et al.Treatment effect of Qingfei Paidu decoction combined with conventional treatment on COVID-19 patients and other respiratory diseases: a multicenter retrospective case series. Front Pharmacol. 2022;13:849598.

[[74]] Liao Y, Yin B, Jin Z, et al.TCM theoretical analysis and modern pharmacological mechanism of Huashi Baidu decoction in treating severe novel coronavirus pneumonia. [J] Hainan Med Coll. 2020;26:1209-1213.

[[75]] Wang Y, Lu C, Li H, et al.Efficacy and safety assessment of severe COVID-19 patients with Chinese medicine: a retrospective case series study at early stage of the COVID-19 epidemic in Wuhan, China. [J] Ethnopharmacol. 2021;277:113888.

[[76]] Li Q, Wang H, Li X, et al.The role played by traditional Chinese medicine in preventing and treating COVID-19 in China. Front Med. 2020;14(5):681-688.

[[77]] Shi N, Guo L, Liu B, et al. Efficacy and safety of Chinese herbal medicine versus lopinavir-ritonavir in adult patients with coronavirus disease 2019: a non-randomized controlled trial. Phytomedicine. 2021;81:153367.

[[78]] Xiong WZ, Wang G, Du J, et al. Efficacy of herbal medicine (Xuanfei Baidu decoction) combined with conventional drug in treating COVID-19: a pilot randomizedclinical trial. Integr Med Res. 2020;9(3):100489.

[[79]] Li F, Li YJ, Zhang JX, et al.The therapeutic efficacy of Xuanfei Baidu Formula combined with conventional drug in the treatment of coronavirus disease 2019: a protocol for systematic review and meta-analysis. Medicine. 2021;100(3):e24129.

[[80]] Zhou L, Wang XN, Liu XK, et al.Report on the case of Xuanfei Baidu recipe for curing COVID-19’s critically ill patients. [J] Tianjin Univ Tradit Chin Med. 2021;38(5):556-559.

[[81]] Pan X, Dong L, Yang L, et al.Potential drugs for the treatment of the novel coronavirus pneumonia (COVID-19) in China. Virus Res. 2020;286:198057.

[[82]] Li XC, Zhang J, Xia WG, et al. Clinical observation of Xuanfei Baidu decoction in treatment of severe coronavirus disease 2019 (COVID-19). Zhongguo Zhong Yao Za Zhi. 2022;47(13):3667-3674.

[[83]] Zhang QS, Cao F, Wang YF, et al. The efficacy and safety of Jinhua Qinggan granule (JHQG) in the treatment of coronavirus disease 2019 (COVID-19): a protocol for systematic review and meta analysis. Medicine (Baltim). 2020;99(24):e20531.

[[84]] An XD, Xu X, Xiao MZ, et al. Efficacy of Jinhua Qinggan granules combined with western medicine in the treatment of confirmed and suspected COVID-19: a randomized controlled trial. Front Med (Lausanne). 2021;8:728055.

[[85]] Shah MR, Fatima S, Khan SN, et al. Jinhua Qinggan granules for non-hospitalized COVID-19 patients: a double-blind, placebo-controlled, and randomized controlled trial. Front Med (Lausanne). 2022;9:928468.

[[86]] Lin TPH, Lau EMC, Wan KH, et al. Initial observations of Jinhua Qinggan granules, a Chinese medicine, in the mitigation of hospitalization and mortality in high-risk elderly with COVID-19 infection: a retrospective study in an old age home in Hong Kong. Front Med (Lausanne). 2022;9:948149.

[[87]] Xiao MZ, Tian JX, Zhou YN, et al. Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: a randomized controlled trial. Pharmacol Res. 2020;161:105126.

[[88]] Shen XH, Yin FG. The mechanisms and clinical application of traditional Chinese medicine Lianhua-Qingwen capsule. Biomed Pharmacother. 2021;142:111998.

[[89]] Zeng MJ, Li LJ, Wu ZQ. Traditional Chinese medicine Lianhua Qingwen treating corona virus disease 2019 (COVID-19): meta-analysis of randomized controlled trials. PLoS One. 2020;15(9):e0238828.

[[90]] Fan SJ, Liao JK, Wei L, et al. Treatment efficacy of Lianhua Qingwen capsules for eraly-stage COVID-19. Am [J] Transl Res. 2022;14(2):1332-1338.

[[91]] Guo H, Zheng JY, Huang G, et al.Xuebijing injection in the treatment of COVID-19: a retrospective case-control study. Ann Palliat Med. 2020;9(5):3235-3248.

[[92]] Luo ZJ, Chen W, Xiang MQ, et al. The preventive effect of Xuebijing injection against cytokine storm for severe patients with COVID-19: a prospective randomized controlled trial. Eur [J] Integr Med. 2021;42:101305.

[[93]] Chen L, Zhang A, Li QT, et al. Evaluation of clinical value of Xuebijing combined with human immunoglobulin in severe and critically ill patients with coronavirus disease 2019. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021;33(4):399-404.

[[94]] Liu XS, Song YL, Guan WJ, et al.A multicenter prospective cohort study of Xuebijing injection in the treatment of severe coronavirus disease 2019. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021;33(7):774-778.

[[95]] Fu JM, Wu LL, Ma YY, et al. The efficacy and safety of Xuebijing injection for corona virus disease 2019: a protocol for a systematic review and meta-analysis. Medicine (Baltim). 2020;99(49):e23401.

[[96]] Viana SD, Nunes S, Reis F. ACE2 imbalance as a key player for the poor outcomes in COVID-19 patients with age-related comorbidities-role of gut microbiota dysbiosis. Ageing Res Rev. 2020;62:101123.

[[97]] Perlot T, Penninger JM. ACE2-from the renin-angiotensin system to gut microbiota and malnutrition. Microbes Infect. 2013;15(13):866-873.

[[98]] Liu JJ, Chen QH, Liu SZ, et al. Sini decoction alleviates E. coli induced acute lung injury in mice via equilibrating ACE-AngII-AT1R and ACE2-Ang-(1-7)-Mas axis. Life Sci. 2018;208:139-148.

[[99]] Cinatl J, Morgenstern B, Bauer G, et al.Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003;361(9374):2045-2046.

[[100]] Kadri SS, Boycher HW.U.S. efforts to curb antibiotic resistance-are we saving lives? N Engl [J] Med. 2020;383(9):806-808.

[[101]] Buckel WR, Stenehjem E, Sorensen J, et al.Broad-versus narrow-spectrum oral antibiotic transition and outcomes in health care-associated pneumonia. Ann Am Thorac Soc. 2017;14(2):200-205.

[[102]] Ramirez J, Guarner F, Fernandez LB, et al.Antibiotics as major disruptors of gut microbiota. Front Cell Infect Microbiol. 2020;10:572912.

[[103]] Duan YJ, Chen ZY, Tan L, et al.Gut resistomes, microbiota and antibiotic residues in Chinese patients undergoing antibiotic administration and healthy individuals. Sci Total Environ. 2020;705:135674.

[[104]] Sun XZ, Wang DD, Wei LN, et al.Gut microbiota and SCFAs play key roles in QingFei Yin Recipe anti-streptococcal pneumonia effects. Front Cell Infect Microbiol. 2021;11:791466.

[[105]] Zhu HY, Lu XX, Ling LJ, et al.Houttuynia cordata polysaccharides ameliorate pneumonia severity and intestinal injury in mice with influenza virus infection. [J] Ethnopharmacol. 2018;218:90-99.

[[106]] Jiang WJ, Luo F, Lu QF, et al.The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state. Chem Biol Interact. 2016;243:127-134.

[[107]] Mukherjee S, Hanidziar D.More of the gut in the lung: how two microbiomes meet in ARDS. Yale [J] Biol Med. 2018;91(2):143-149.

[[108]] Dickson RP, Singer BH, Newstead MW, et al.Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome. Nat Microbiol. 2016;1(10):16113.

[[109]] Li Y, Liu XY, Ma MM, et al.Changes in intestinal microflora in rats with acute respiratory distress syndrome. World [J] Gastroenterol. 2014;20(19):5849-5858.

[[110]] Tang TY, Wang F, Liu J, et al.Rhubarb alleviates acute lung injury by modulating gut microbiota dysbiosis in mice. Curr Microbiol. 2022;79(4):116.

[[111]] Lin XT, Liang SS, Wang QH, et al. Metagenomics approach the intestinal microbiome structure and function in the anti-H1N1 of a traditional Chinese medicine acid polusaccharide. Microb Pathog. 2020;147:104351.

[[112]] Chen MY, Li H, Lu XX, et al.Houttuynia cordata polysaccharides alleviated intestinal injury and modulated intestinal microbiota in H1N1 virus infected mice. Chin [J] Nat Med. 2019;17(3):187-197.

[[113]] Rabe KF, Watz H. Chronic obstructive pulmonary disease. Lancet. 2017;389(10082):1931-1940.

[[114]] Riley CM, Sciurba FC. Diagnosis and outpatient management of chronic obstructive pulmonary disease: a review. JAMA. 2019;321(8):786-797.

[[115]] Huang YJ, Erb-Downward JR, Dickson RP, et al. Understanding the role of the microbiome in chronic obstructive pulmonary disease: principles, challenges, and future directions. Transl Res. 2017;179:71-83.

[[116]] Bowerman KL, Rehman SF, Vaughan A, et al. Disease-associated gut microbiome and metabolome changes in patients with chronic obstructive pulmonary disease. Nat Commun. 2020;11(1):5886.

[[117]] Sun Z, Shen Y ZQ, et al.Dynamic changes of gut and lung microorganisms during chronic obstructive pulmonary disease exacerbations. Kaohsiung [J] Med Sci. 2020;36(2):107-113.

[[118]] Huang P, Huang T, Li DS, et al.Treating chronic obstructive pulmonary disease-integrated network pharmacology and molecular docking. Evid Based Complement Alternat Med. 2021;2021:5532009.

[[119]] Hong ML, Chen WX, Cai SH, et al. Study on the intervention effect of Yufeining on pulmonary function in patients with chronic obstructive pulmonary disease. Chin [J] Trad Chin Med. 2005;20:92-95.

[[120]] Hong ML, Yang GZ, Chen WX, et al. Effect of Yufeining on induced sputum interleukin-8 in patients with chronic obstructive pulmonary disease at the stable phase. Chin [J] Integr Med. 2005;11:179-182.

[[121]] Hong ML, Hong CL, Chen HN, et al. Effects of the Chinese herb formula Yufeining on stable chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled trial. Medicine (Baltim). 2018;97(39):e12461.

[[122]] Campo P, Rodríguez F, Sánchez-García S, et al.Phenotypes and endotypes of uncontrolled severe asthma: new treatments. [J] Investig Allergol Clin Immunol. 2013;23(2):76-88.

[[123]] Frati F, Salvatori C, Incorvaia C, et al. The role of the microbiome in asthma: the gut-lung axis. Int [J] Mol Sci. 2018;20(1):123.

[[124]] Gangi AD, Cicco MED, Comberiati P, et al.Go with your gut: the shaping of T-cell response by gut microbiota in allergic asthma. Front Immunol. 2020;11:1485.

[[125]] He Q, Liu C, Shen L, et al.Theory of the exterior-interior relationship between the lungs and the large intestine to explore the mechanism of Eriobotrya japonica leaf water extract in the treatment of cough variant asthma. [J] Ethnopharmacol. 2021;281:114482.

[[126]] Dong YM, Yan H, Zhao X, et al.Gu-Ben-Fang-Xiao decoction ameliorated murine asthma in remission stage by modulating microbiota-acetate-tregs axis. Front Pharmacol. 2020;11:549.

[[127]] Hsu WH, Lin LJ, Lu CK, et al.Effect of You-Gui-Wan on house dust mite-induced mouse allergic asthma via regulating amino acid metabolic disorder and gut dysbiosis. Biomolecules. 2021;11(6):812.

[[128]] Holshue ML, Debolt C, Lindquist S, et al.First case of 2019 novel coronavirus in the united states. N Engl [J] Med. 2020;382(10):929-936.

[[129]] Papoutsis A, Borody T, Dolai S, et al. Detection of SARS-CoV-2 from patient fecal samples by whole genome sequencing. Gut Pathog. 2021;13(1):7.

[[130]] Chen S, Si JF, Tang WQ, et al.An asymptomatic SARS-CoV-2-infected infant with persistent fecal viral RNA shedding in a family cluster: a rare case report. Front Med (Lausanne). 2020;7:562875.

[[131]] Wong MC, Huang JJ, Lai C, et al.Detection of SARS-CoV-2 RNA in fecal specimens of patients with confirmed COVID-19: a meta-analysis. [J] Infect. 2020;81(2):e31-e38.

[[132]] Adhikari UD, Eng G, Farcasanu M, et al. Fecal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is associated with decreased coronavirus disease 2019 (COVID-19) survival. Clin Infect Dis. 2022;74(6):1081-1084.

[[133]] Wu GS, Zhong J, Zheng NN, et al.Investigation of modulating effect of Qingfei Paidu Decoction on host metabolism and gut microbiome in rats. Chin [J] Chin Mater Med. 2020;45:3726-3739.