The Regional Landscape of the Human Colon Culturome in Health and Cystic Fibrosis

preprint OA: closed CC-BY-NC-ND-4.0
📄 Open PDF Full text JSON View at publisher

Abstract

Cystic fibrosis (CF) alters gut physiology, yet its impact on microbial communities across colonic regions (ascending, transverse, descending colon) and microhabitats (lumen, mucosa) remains incompletely understood. Here, we applied culturomics to characterize gut microbiota in 32 individuals (22 nonCF, 10 CF). Persons with CF (pwCF) exhibited significantly higher viable bacterial loads than nonCF individuals, particularly in mucosal samples. Anaerobes predominated overall, with relative enrichment of aerobes in the mucosa of pwCF. Alpha diversity was reduced in mucosal samples and aerobic cultures for pwCF, whereas beta diversity was influenced by all the tested variables except the colonic region. Phylum-level analyses revealed enrichment of Proteobacteria and depletion of Actinobacteria, Bacteroidota, and Firmicutes in samples from pwCF, consistent with stool analysis. Random forest models identified selected oral-associated microbes as key predictive taxa and accurately classified polyp status with very high accuracy. Whole-genome sequencing of Bacteroides fragilis (n=21) and Escherichia coli (n=15) isolates, representing a subset of 109 gut bacterial genomes sequenced from this cohort, revealed minimal genomic variation across colonic regions and sample types, indicating intra-individual strain stability. The understandings from this pilot culturome study may help in developing targeted microbial therapeutic approaches to address the gut dysbiosis of CF. Importance This pilot study represents the first culturome analysis of the cystic fibrosis colon. Our preliminary findings demonstrate that CF-associated gut dysbiosis is spatially specific, with mucosal bacterial communities showing pronounced alterations while luminal communities remain unchanged. This spatial specificity suggests the mucosal microenvironment as a potential therapeutic target and indicates that interventions focused solely on luminal bacteria may be insufficient. The promising predictive accuracy of culturome-based machine learning models in this small cohort suggests these viable bacterial signatures could serve as biomarkers for CF management pending larger validation studies. Additionally, our initial observations of complex CFTR modulator effects on gut microbial communities provide insights for future studies optimizing combination therapies.
Full text 8,980 characters · extracted from preprint-html · click to expand
The Regional Landscape of the Human Colon Culturome in Health and Cystic Fibrosis | bioRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (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];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-M677548'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results The Regional Landscape of the Human Colon Culturome in Health and Cystic Fibrosis View ORCID Profile Sarvesh Surve , Rebecca Valls , View ORCID Profile Kaitlyn Barrack , Lorraine Gwilt , Timothy B Gardner , View ORCID Profile George O'Toole doi: https://doi.org/10.1101/2025.09.29.679198 Sarvesh Surve 1 Geisel School of Medicine at Dartmouth; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sarvesh Surve Rebecca Valls 2 Geisel School of medicine at Dartmouth; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Kaitlyn Barrack 1 Geisel School of Medicine at Dartmouth; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Kaitlyn Barrack Lorraine Gwilt 3 Dartmouth Hitchcock Medical Center; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Timothy B Gardner 4 Dartmouth-Hitchcock Medical Center Find this author on Google Scholar Find this author on PubMed Search for this author on this site George O'Toole 1 Geisel School of Medicine at Dartmouth; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for George O'Toole For correspondence: georgeo{at}dartmouth.edu Abstract Info/History Metrics Supplementary material Preview PDF Abstract Cystic fibrosis (CF) alters gut physiology, yet its impact on microbial communities across colonic regions (ascending, transverse, descending colon) and microhabitats (lumen, mucosa) remains incompletely understood. Here, we applied culturomics to characterize gut microbiota in 32 individuals (22 nonCF, 10 CF). Persons with CF (pwCF) exhibited significantly higher viable bacterial loads than nonCF individuals, particularly in mucosal samples. Anaerobes predominated overall, with relative enrichment of aerobes in the mucosa of pwCF. Alpha diversity was reduced in mucosal samples and aerobic cultures for pwCF, whereas beta diversity was influenced by all the tested variables except the colonic region. Phylum-level analyses revealed enrichment of Proteobacteria and depletion of Actinobacteria, Bacteroidota, and Firmicutes in samples from pwCF, consistent with stool analysis. Random forest models identified selected oral-associated microbes as key predictive taxa and accurately classified polyp status with very high accuracy. Whole-genome sequencing of Bacteroides fragilis (n=21) and Escherichia coli (n=15) isolates, representing a subset of 109 gut bacterial genomes sequenced from this cohort, revealed minimal genomic variation across colonic regions and sample types, indicating intra-individual strain stability. The understandings from this pilot culturome study may help in developing targeted microbial therapeutic approaches to address the gut dysbiosis of CF. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Cystic Fibrosis Foundation, https://ror.org/00ax59295 , OTOOLE22G0 National Institutes of Health , R01-ES033988 , P30-DK117469 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . View the discussion thread. Back to top Previous Next Posted September 29, 2025. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following The Regional Landscape of the Human Colon Culturome in Health and Cystic Fibrosis Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share The Regional Landscape of the Human Colon Culturome in Health and Cystic Fibrosis Sarvesh Surve , Rebecca Valls , Kaitlyn Barrack , Lorraine Gwilt , Timothy B Gardner , George O'Toole bioRxiv 2025.09.29.679198; doi: https://doi.org/10.1101/2025.09.29.679198 Share This Article: Copy Citation Tools The Regional Landscape of the Human Colon Culturome in Health and Cystic Fibrosis Sarvesh Surve , Rebecca Valls , Kaitlyn Barrack , Lorraine Gwilt , Timothy B Gardner , George O'Toole bioRxiv 2025.09.29.679198; doi: https://doi.org/10.1101/2025.09.29.679198 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Microbiology Subject Areas All Articles Animal Behavior and Cognition (7618) Biochemistry (17633) Bioengineering (13856) Bioinformatics (41841) Biophysics (21399) Cancer Biology (18529) Cell Biology (25422) Clinical Trials (138) Developmental Biology (13352) Ecology (19860) Epidemiology (2067) Evolutionary Biology (24282) Genetics (15582) Genomics (22462) Immunology (17700) Microbiology (40295) Molecular Biology (17140) Neuroscience (88419) Paleontology (666) Pathology (2823) Pharmacology and Toxicology (4813) Physiology (7632) Plant Biology (15107) Scientific Communication and Education (2042) Synthetic Biology (4284) Systems Biology (9808) Zoology (2267)

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
unpaywall
last seen: 2026-05-24T02:00:01.246996+00:00
License: CC-BY-NC-ND-4.0