Regulating the distortion of bacteria and metabolism by hydrogen in allergic rhinitis

Regulating the distortion of bacteria and metabolism by hydrogen in allergic rhinitis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Regulating the distortion of bacteria and metabolism by hydrogen in allergic rhinitis Nan Wang, Xingyue Zheng, Qianzi Ma, Junjie Liu, Wanchao Yang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5180950/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Hydrogen is known to improve allergic rhinitis. Nasal flora that are different from those of healthy normal subjects have been detected in the nasal cavity of patients with allergic rhinitis (AR), and the flora can influence the metabolic levels of both themselves and their hosts. In addition, hydrogen has been shown to affect flora distribution and diversity. These findings suggest that hydrogen may target the nasal flora and metabolites to treat AR. Therefore, further in-depth exploration of the specific mechanism of action of hydrogen in the treatment of allergic rhinitis is necessary to provide a more scientific and effective program for the treatment of this disease. Methods The serum eosinophil count (EOS), immunoglobulin E (IgE) concentration, visual analogue scale (VAS) score, total nasal symptom score (TNSS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used before and after hydrogen inhalation in AR patients. The skin prick test (SPT) was used to determine allergen sensitization. The community composition and relative abundance of the nasal flora were examined before and after hydrogen inhalation and in healthy subjects via 16S rRNA gene sequencing. Liquid chromatography‒mass spectrometry (LC‒MS) was used to explore the metabolic profile. Results There were no adverse reactions during or after hydrogen inhal ation in AR patients, and the safety was good, with significant improvem ents in the VAS, TNSS, EOS, and IgE scores (P<0.05). The results of 16 S rRNA gene sequencing of nasal flora revealed that the distribution and diversity of nasal flora in AR patients were significantly altered after hydrogen inhalation compared with those before hydrogen inhalation and were closer to those of normal individuals. We also found that the metabolites 19(R)-hydroxy-prostaglandin E2, arachidonic acid (AA), LEP 20:2, LEP O-18:2, LEP O-22:3, LPS 18:1, and LPS 20:3 were significantly more abun dant than normal in nasal secretions in AR and then significantly decreased and approached normal levels after being modulated by hydrogen. 19(R) -Hydroxy-prostaglandin E2 levels were positively correlated with the abund ance of Devosia, Paenibacillus, and colonies in the nasal cavity. AA was significantly positively correlated with Muribaculum bacteria and negatively correlated with [Eubacterium]_ruminantium_group. LPE was positively correlated with the bacteria Paenibacillus and Muribaculum and negatively correlated with [Eubacterium]_ruminantium_group. LPS was negatively correlated with [Eubacterium]_ruminantium_group and UCG-002 and positively correlated with Devosia and Muribaculum. Conclusions H2 may improve symptoms in AR patients by modulating nasalflora distribution and metabolite levels. Allergic rhinitis Nasal flora Metabolites Hydrogen Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Full Text Additional Declarations Table 1 is available in the Supplementary Files section. Supplementary Files table1.xlsx Table 1 Baseline analysis between HCs and patients with AR. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5180950","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":391480431,"identity":"20aa2725-d412-4862-9466-fd33dfc1b28e","order_by":0,"name":"Nan Wang","email":"","orcid":"","institution":"Qingdao Women and Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Nan","middleName":"","lastName":"Wang","suffix":""},{"id":391480432,"identity":"8660a4b4-adf8-47d4-8e92-b6341d38e463","order_by":1,"name":"Xingyue Zheng","email":"","orcid":"","institution":"Second Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xingyue","middleName":"","lastName":"Zheng","suffix":""},{"id":391480433,"identity":"9b9d8861-114f-4218-a820-a3379e7099a1","order_by":2,"name":"Qianzi Ma","email":"","orcid":"","institution":"Second Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qianzi","middleName":"","lastName":"Ma","suffix":""},{"id":391480434,"identity":"034eaddd-ab3c-45d0-b7ad-b7a0cdb51877","order_by":3,"name":"Junjie Liu","email":"","orcid":"","institution":"Second Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Junjie","middleName":"","lastName":"Liu","suffix":""},{"id":391480435,"identity":"120250c7-03cd-4609-a718-b9276c01cb77","order_by":4,"name":"Wanchao Yang","email":"","orcid":"","institution":"Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Wanchao","middleName":"","lastName":"Yang","suffix":""},{"id":391480436,"identity":"6cc4d6e2-0cca-4112-ac61-c5bf52e8fb9a","order_by":5,"name":"Yanan Sun","email":"","orcid":"","institution":"Second Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yanan","middleName":"","lastName":"Sun","suffix":""},{"id":391480437,"identity":"100354da-73db-4205-bd1e-19a508e51ab3","order_by":6,"name":"Yanlu Che","email":"","orcid":"","institution":"Second Affiliated Hospital of Harbin Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yanlu","middleName":"","lastName":"Che","suffix":""},{"id":391480438,"identity":"6cbd8a16-3020-4b4c-9634-b71f8c4f2414","order_by":7,"name":"Jingting Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYBAC+4bjhx98bGBIAPN4iNFiwHgmzXAmaVqYDxhI85KkxZztQIKx7Y57ebozEhgfvG1jkDcnpMWy5+CBx7lniovNbiQwG85tYzDc2UBIzw2gLbltCYnbbiSwSfO2MSQYHCCk5f4DA2lLiBb230RpMTgA9D4j1BZmorRINgADubctodjszMNmyTnnJAw3ENLCzwCMyp9tCXlmx5MPfnhTZiNP2C8IwNgAJCSIVz8KRsEoGAWjADcAAJ+hR1o6gPhfAAAAAElFTkSuQmCC","orcid":"","institution":"Harbin Medical College: Harbin Medical University","correspondingAuthor":true,"prefix":"","firstName":"Jingting","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-09-30 12:50:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5180950/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5180950/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72286010,"identity":"d7933b29-9dec-41e6-87b5-ea759fac56f7","added_by":"auto","created_at":"2024-12-24 16:56:10","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":103284,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of Block, Snot, Itch, Sneeze, VAS, TNSS, RQLQ, EOS, and IgE scores between the HI pregroup and HI postgroup.\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5180950/v1/067774ddc1fd70c3d7178a90.png"},{"id":72286013,"identity":"964b957d-3bfd-41ef-967b-e001d8917686","added_by":"auto","created_at":"2024-12-24 16:56:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":207831,"visible":true,"origin":"","legend":"\u003cp\u003eDifferences in microbial diversity in the nasal secretions of healthy normal subjects and AR patients before and after hydrogen inhalation. A‒C Microbial diversity was significantly lower in the HI post group than in the HI pre group, as estimated by the observed_features index, Chao 1 index, and Shannon index. D Microbial composition of microorganisms at the phylum level in the nasal secretions of normal subjects and AR patients before and after hydrogen inhalation. E-I Comparison of the microbiota at the genus level among the three groups.\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5180950/v1/2bbb83b62eb06a09343f1b78.png"},{"id":72286012,"identity":"83e9b2d8-8c54-4f16-a7cb-6a61952d9815","added_by":"auto","created_at":"2024-12-24 16:56:10","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":597393,"visible":true,"origin":"","legend":"\u003cp\u003eSpecific characterization of the microbiota among the three groups via LEfSe (LDA effect size) analysis. A Histogram of LDA scores showing significant differences in microbe type and abundance among the three groups. B Cladogram generated by LEfSe representing the taxonomic hierarchical structure of the identified microbial populations. In the evolutionary branching diagram, circles radiating from inside to outside represent taxonomic levels from phylum to genus (or species). Each small circle at a different taxonomic level represents a taxon at that level, and the size of the circle diameter is proportional to the relative abundance size. Species with no significant differences are coloured uniformly in yellow, and differentiated species are coloured following the group, with red nodes indicating microbial taxa that play an important role in the red group and green nodes indicating microbial taxa that play an important role in the green group.\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5180950/v1/0be4aca3716b8c3dd866ce3b.png"},{"id":72286015,"identity":"d80a4287-fcfd-47ba-837f-d6f4483e4af8","added_by":"auto","created_at":"2024-12-24 16:56:10","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":748908,"visible":true,"origin":"","legend":"\u003cp\u003eA-D COG functional enrichment analysis of microbial genes between the HC and HI pre groups and COG functional enrichment analysis of microbial genes between the HI pre- and HI postgroups. E Vertical is the information of the environmental factors; horizontal is the information of the species; the value corresponding to the middle heatmap is the Spearman correlation coefficient r, which is between -1 and 1; r\u0026lt;0 is a negative correlation; r\u0026gt;0 is a positive correlation; and \"*\" denotes the p value of the significance test \u0026lt;0.05.\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5180950/v1/40fc6da50d0986c486139559.png"},{"id":72286019,"identity":"d5c1bcc1-8c12-4537-ada8-ad43cef6b7ef","added_by":"auto","created_at":"2024-12-24 16:56:10","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":713106,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of metabolome among the HC, HI pre- and HI postintervention groups. A-B PLS-DA model validation based on sevenfold cross-validation and 200 permutation tests. C-D The overall distribution of differentially abundant metabolites. E‒F Matchstick plots of different metabolites. G Heatmap of the differentially abundant metabolites among the three groups.\u003c/p\u003e","description":"","filename":"figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-5180950/v1/949351a6ca3b0bd990ade9cc.png"},{"id":72286014,"identity":"0d134946-086d-438f-a40c-e729f6f4b605","added_by":"auto","created_at":"2024-12-24 16:56:10","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":883233,"visible":true,"origin":"","legend":"\u003cp\u003eA-B In the correlation diagram of differentially abundant metabolites, the highest correlation is 1, which is a complete positive correlation (red); the lowest correlation is -1, which is a complete negative correlation (blue); and the part without color indicates a P value \u0026gt; 0.05. C-D KEGG enrichment bubble diagram, where the horizontal coordinate is x/y (the number of differentially abundant metabolites in the corresponding metabolic pathway/the total number of identified metabolites in the pathway); the higher the value is, the higher the concentration of differentially abundant metabolites in the pathway. The color of the dots represents the P value of the hypergeometric test, and the size of the dots represents the number of differentially abundant metabolites in the corresponding pathway. E Correlation heatmap; horizontal represents different bacteria, vertical represents different metabolites, the right side of the legend represents the correlation coefficient, red represents a positive correlation, and blue represents a negative correlation.\u003c/p\u003e","description":"","filename":"figure6.png","url":"https://assets-eu.researchsquare.com/files/rs-5180950/v1/301343ae999ee1d3ce06c345.png"},{"id":73113310,"identity":"ac8e0db5-16ba-4891-a1f0-944689914972","added_by":"auto","created_at":"2025-01-06 23:19:17","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1711264,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5180950/v1_covered_b1ab4587-c326-475a-b30a-2d24aaf69434.pdf"},{"id":72286011,"identity":"7d55d684-4eb9-40bb-af50-8453dba60556","added_by":"auto","created_at":"2024-12-24 16:56:10","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":9329,"visible":true,"origin":"","legend":"\u003cp\u003eTable 1 Baseline analysis between HCs and patients with AR.\u003c/p\u003e","description":"","filename":"table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-5180950/v1/97d1a4d02da635e05fb77136.xlsx"}],"financialInterests":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e","formattedTitle":"Regulating the distortion of bacteria and metabolism by hydrogen in allergic rhinitis","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Allergic rhinitis, Nasal flora, Metabolites, Hydrogen","lastPublishedDoi":"10.21203/rs.3.rs-5180950/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5180950/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHydrogen is known to improve allergic rhinitis. Nasal flora that are different from those of healthy normal subjects have been detected in the nasal cavity of patients with allergic rhinitis (AR), and the flora can influence the metabolic levels of both themselves and their hosts. In addition, hydrogen has been shown to affect flora distribution and diversity. These findings suggest that hydrogen may target the nasal flora and metabolites to treat AR. Therefore, further in-depth exploration of the specific mechanism of action of hydrogen in the treatment of allergic rhinitis is necessary to provide a more scientific and effective program for the treatment of this disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe serum eosinophil count (EOS), immunoglobulin E (IgE) concentration, visual analogue scale (VAS) score, total nasal symptom score (TNSS), and rhinoconjunctivitis quality of life questionnaire (RQLQ) were used before and after hydrogen inhalation in AR patients. The skin prick test (SPT) was used to determine allergen sensitization. The community composition and relative abundance of the nasal flora were examined before and after hydrogen inhalation and in healthy subjects via 16S rRNA gene sequencing. Liquid chromatography‒mass spectrometry (LC‒MS) was used to explore the metabolic profile.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were no adverse reactions during or after hydrogen inhal ation in AR patients, and the safety was good, with significant improvem ents in the VAS, TNSS, EOS, and IgE scores (P\u0026lt;0.05). The results of 16 S rRNA gene sequencing of nasal flora revealed that the distribution and diversity of nasal flora in AR patients were significantly altered after hydrogen inhalation compared with those before hydrogen inhalation and were closer to those of normal individuals. We also found that the metabolites 19(R)-hydroxy-prostaglandin E2, arachidonic acid (AA), LEP 20:2, LEP O-18:2, LEP O-22:3, LPS 18:1, and LPS 20:3 were significantly more abun dant than normal in nasal secretions in AR and then significantly decreased and approached normal levels after being modulated by hydrogen. 19(R) -Hydroxy-prostaglandin E2 levels were positively correlated with the abund ance of Devosia, Paenibacillus, and colonies in the nasal cavity. AA was significantly positively correlated with Muribaculum bacteria and negatively correlated with [Eubacterium]_ruminantium_group. LPE was positively correlated with the bacteria Paenibacillus and Muribaculum and negatively correlated with [Eubacterium]_ruminantium_group. LPS was negatively correlated with [Eubacterium]_ruminantium_group and UCG-002 and positively correlated with Devosia and Muribaculum.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eH2 may improve symptoms in AR patients by modulating nasalflora distribution and metabolite levels.\u003c/p\u003e","manuscriptTitle":"Regulating the distortion of bacteria and metabolism by hydrogen in allergic rhinitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-24 16:56:06","doi":"10.21203/rs.3.rs-5180950/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8fb18504-9cc3-421a-b93f-1efa8036b2d2","owner":[],"postedDate":"December 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-06T23:11:05+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-24 16:56:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5180950","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5180950","identity":"rs-5180950","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}