Salivary bacterial signatures in depression-obesity comorbidity are associated with neurotransmitters and neuroactive dipeptides

Salivary bacterial signatures in depression-obesity comorbidity are associated with neurotransmitters and neuroactive dipeptides | 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 Salivary bacterial signatures in depression-obesity comorbidity are associated with neurotransmitters and neuroactive dipeptides Suzi Hong, Gajender Aleti, Jordan N. Kohn, Emily A. Troyer, Kelly Weldon, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-829379/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background Depression and obesity, both of which are highly prevalent and inflammation underlies, often co-occur. Microbiome perturbations are implicated in obesity-inflammation-depression interrelationships, but how microbiome alterations contribute to underlying pathologic processes remains unclear. Metabolomic investigations to uncover microbial neuroactive metabolites may offer mechanistic insights into host-microbe interactions. Methods Using 16S sequencing and untargeted mass spectrometry of saliva, and blood monocyte inflammation regulation assays, we determined key microbes, metabolites and host inflammation in association with depressive symptomatology, obesity, and depressive symptomatology-obesity comorbidity. Results Gram-negative bacteria with inflammation potential were enriched relative to Gram-positive bacteria in comorbid obesity-depression, supporting the inflammation-oral microbiome link in obesity-depression interrelationships. Oral microbiome was highly predictive of depressive symptomatology-obesity co-occurrences than obesity and depressive symptomatology independently, suggesting specific microbial signatures associated with obesity-depression co-occurrences. Mass spectrometry analysis revealed significant changes in levels of signaling molecules of microbiota, microbial or dietary derived signaling peptides and aromatic amino acids among host phenotypes. Furthermore, integration of the microbiome and metabolomics data revealed that key oral microbes, many previously shown to have neuroactive potential, co-occurred with potential neuropeptides and biosynthetic precursors of the neurotransmitters dopamine, epinephrine and serotonin. Conclusions Together, our findings offer novel insights into oral microbial-brain connection and potential neuroactive metabolites involved. General Microbiology Applied & Industrial Microbiology depressive symptomatology obesity depressive symptomatology-obesity comorbidity symptomatology independently Full Text Supplementary Files Supplementarytables.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Review # 1 received at journal 21 Oct, 2021 Reviewer # 2 agreed at journal 21 Sep, 2021 Reviewer # 1 agreed at journal 19 Sep, 2021 Reviewers invited by journal 16 Sep, 2021 Editor assigned by journal 08 Sep, 2021 Submission checks completed at journal 27 Aug, 2021 Editor invited by journal 23 Aug, 2021 First submitted to journal 17 Aug, 2021 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. 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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-829379","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":47033036,"identity":"c7120ee8-37d2-46af-add3-3e2fd7d702b1","order_by":0,"name":"Suzi Hong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA90lEQVRIiWNgGAWjYDACZh4QaZMAZDUwQ4SAbB58WtjBsmlAZYyNzcRp4QfLHiZBi3wz78HHBb/O5/GzH2x/XMBwWF6+PYHxwds23FoMDvMlG8/su10s2ZPY2DyD4bDhhjMPmA3n4tPCzGMmzdtzO3HDAaAWHqALDSQS2KR58WiRbwZrOZe4//xDiBb5GQnsv/FpYTgM1MLz40DiBgmoLQw3EtiY8WkxOMxjbMzbkJw448bDxtk8BulAvzxslpxzDo/D+s8YPub5Y5fY35984DNPhTUwxJIPfnhThsdhIMAId4YBmNtAQD0I/CFCzSgYBaNgFIxcAABgMlIT3CaofAAAAABJRU5ErkJggg==","orcid":"","institution":"University of California San Diego","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Suzi","middleName":"","lastName":"Hong","suffix":""},{"id":47538707,"identity":"b4023edc-be82-48bc-9daa-40d9364122d5","order_by":1,"name":"Gajender Aleti","email":"","orcid":"","institution":"University of California San Diego","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gajender","middleName":"","lastName":"Aleti","suffix":""},{"id":47538708,"identity":"102f7282-b4eb-4809-85f7-11a932a33f7a","order_by":2,"name":"Jordan N. 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Microbiome perturbations are implicated in obesity-inflammation-depression interrelationships, but how microbiome alterations contribute to underlying pathologic processes remains unclear. Metabolomic investigations to uncover microbial neuroactive metabolites may offer mechanistic insights into host-microbe interactions. \u003c/p\u003e\u003cp\u003eMethods\u003c/p\u003e\u003cp\u003eUsing 16S sequencing and untargeted mass spectrometry of saliva, and blood monocyte inflammation regulation assays, we determined key microbes, metabolites and host inflammation in association with depressive symptomatology, obesity, and depressive symptomatology-obesity comorbidity. \u003c/p\u003e\u003cp\u003eResults\u003c/p\u003e\u003cp\u003eGram-negative bacteria with inflammation potential were enriched relative to Gram-positive bacteria in comorbid obesity-depression, supporting the inflammation-oral microbiome link in obesity-depression interrelationships. Oral microbiome was highly predictive of depressive symptomatology-obesity co-occurrences than obesity and depressive symptomatology independently, suggesting specific microbial signatures associated with obesity-depression co-occurrences. Mass spectrometry analysis revealed significant changes in levels of signaling molecules of microbiota, microbial or dietary derived signaling peptides and aromatic amino acids among host phenotypes. Furthermore, integration of the microbiome and metabolomics data revealed that key oral microbes, many previously shown to have neuroactive potential, co-occurred with potential neuropeptides and biosynthetic precursors of the neurotransmitters dopamine, epinephrine and serotonin. \u003c/p\u003e\u003cp\u003eConclusions\u003c/p\u003e\u003cp\u003eTogether, our findings offer novel insights into oral microbial-brain connection and potential neuroactive metabolites involved.\u003c/p\u003e","manuscriptTitle":"Salivary bacterial signatures in depression-obesity comorbidity are associated with neurotransmitters and neuroactive dipeptides","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-08-23 14:48:05","doi":"10.21203/rs.3.rs-829379/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2021-10-22T00:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable due to the journal's policy.\n"},{"type":"reviewerAgreed","content":"","date":"2021-09-22T00:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2021-09-20T00:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-09-17T00:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-09-09T00:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-08-27T15:14:22+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-08-24T00:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2021-08-18T00:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-microbiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mcro","sideBox":"Learn more about [BMC Microbiology](http://bmcmicrobiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/mcro","title":"BMC Microbiology","twitterHandle":"#bmcmicrobiology","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9f292113-0807-4466-a810-220085918e9b","owner":[],"postedDate":"August 23rd, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":6628934,"name":"General Microbiology"},{"id":6628935,"name":"Applied \u0026 Industrial Microbiology"}],"tags":[],"updatedAt":"2022-02-25T11:35:11+00:00","versionOfRecord":[],"versionCreatedAt":"2021-08-23 14:48:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-829379","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-829379","identity":"rs-829379","version":["v1"]},"buildId":"ehx78VzkSd0WSzXnipQa-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}