{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T06:25:04Z","timestamp":1772173504381,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013222","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000}}],"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T00:00:00Z","timestamp":1752451200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Many microbial communities in nature are complex, with hundreds of coexisting strains and the resources they consume. We currently lack the ability to assemble and manipulate such communities in a predictable manner in the lab. Here, we take a first step in this direction by introducing and studying a simplified consumer resource model of such complex communities in serial dilution experiments. The main assumption of our model is that during the growth phase of the cycle, strains share resources and produce metabolic byproducts in proportion to their average abundances and strain-specific consumption\/production fluxes. We fit the model to describe serial dilution experiments in hCom2, a defined synthetic human gut microbiome with a steady-state diversity of 63 species growing on a rich media, using consumption and production fluxes inferred from metabolomics experiments. The model predicts serial dilution dynamics reasonably well, with a correlation coefficient between predicted and observed strain abundances as high as 0.8. We applied our model to: (i) calculate steady-state abundances of leave-one-out communities and use these results to infer the interaction network between strains; (ii) explore direct and indirect interactions between strains and resources by increasing concentrations of individual resources and monitoring changes in strain abundances; (iii) construct a resource supplementation protocol to maximally equalize steady-state strain abundances.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013222","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T17:37:52Z","timestamp":1752514672000},"page":"e1013222","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Coarse-grained model of serial dilution dynamics in synthetic human gut microbiome"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3453-9517","authenticated-orcid":true,"given":"Tarun","family":"Mahajan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3701-492X","authenticated-orcid":true,"given":"Sergei","family":"Maslov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"issue":"7415","key":"pcbi.1013222.ref001","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nature11550","article-title":"Diversity, stability and resilience of the human gut microbiota","volume":"489","author":"CA Lozupone","year":"2012","journal-title":"Nature."},{"key":"pcbi.1013222.ref002","first-page":"197","volume-title":"Thehuman gut microbiome in health and disease. Metagenomics","author":"J Jovel","year":"2018"},{"key":"pcbi.1013222.ref003","first-page":"43","article-title":"Prokaryotic and eukaryotic diversity of the human gut","volume":"72","author":"JR Marchesi","year":"2010","journal-title":"AdvApplMicrobiol."},{"issue":"3","key":"pcbi.1013222.ref004","first-page":"240","article-title":"Microbial diversity and function in soil: from genes to ecosystems","volume":"5","author":"V Torsvik","year":"2002","journal-title":"CurrOpinMicrobiol."},{"key":"pcbi.1013222.ref005","first-page":"243","article-title":"Microbial diversity in soil: selection of microbial populations by plant and soil type and implications for disease suppressiveness","volume":"42","author":"P Garbeva","year":"2004","journal-title":"AnnuRevPhytopathol."},{"issue":"32","key":"pcbi.1013222.ref006","doi-asserted-by":"crossref","first-page":"12115","DOI":"10.1073\/pnas.0605127103","article-title":"Microbial diversity in the deep sea and the underexplored\u201crare biosphere\u201d","volume":"103","author":"ML Sogin","year":"2006","journal-title":"ProcNatlAcadSciU S A."},{"key":"pcbi.1013222.ref007","first-page":"1325","article-title":"Marine microbial diversity and ecology: importance and future perspectives","author":"S Das","year":"2006","journal-title":"CurrSci."},{"issue":"7195","key":"pcbi.1013222.ref008","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/nature06899","article-title":"Abundance and diversity of microbial life in ocean crust","volume":"453","author":"CM Santelli","year":"2008","journal-title":"Nature."},{"issue":"4","key":"pcbi.1013222.ref009","doi-asserted-by":"crossref","first-page":"3730","DOI":"10.1016\/j.biortech.2010.11.119","article-title":"A meta-analysis of the microbial diversity observed in anaerobic digesters","volume":"102","author":"MC Nelson","year":"2011","journal-title":"BioresourTechnol."},{"key":"pcbi.1013222.ref010","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.biortech.2015.04.015","article-title":"Dynamics of microbial community in a mesophilic anaerobic digester treating food waste:relationship between community structure and process stability","volume":"189","author":"L Li","year":"2015","journal-title":"BioresourTechnol."},{"issue":"19","key":"pcbi.1013222.ref011","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1016\/j.cell.2022.08.003","article-title":"Design, construction, and in vivo augmentation of a complex gut microbiome","volume":"185","author":"AG Cheng","year":"2022","journal-title":"Cell."},{"issue":"12","key":"pcbi.1013222.ref012","first-page":"754","article-title":"Synthetic ecology of the human gut microbiota","volume":"17","author":"G Vrancken","year":"2019","journal-title":"Nat RevMicrobiol."},{"issue":"5","key":"pcbi.1013222.ref013","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1111\/pce.14004","article-title":"High-resolution phenotyping of sorghum genotypic and phenotypic responses to low nitrogen and synthetic microbial communities","volume":"44","author":"YN Chai","year":"2021","journal-title":"Plant Cell Environ."},{"issue":"11","key":"pcbi.1013222.ref014","article-title":"The effects of soil phosphorus content on plant microbiota are driven by the plant phosphate starvation response","volume":"17","author":"OM Finkel","year":"2019","journal-title":"PLoSBiol."},{"issue":"12","key":"pcbi.1013222.ref015","article-title":"Fine-scale diversity of microbial communities due to satellite niches in boom and bust environments","volume":"18","author":"Y Fridman","year":"2022","journal-title":"PLoSComputBiol."},{"issue":"1","key":"pcbi.1013222.ref016","first-page":"6661","article-title":"Complementary resource preferences spontaneously emerge in diauxic microbial communities","volume":"12","author":"Z Wang","year":"2021","journal-title":"NatCommun."},{"issue":"5","key":"pcbi.1013222.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1012049","article-title":"Biodiversity is enhanced by sequential resource utilization and environmental fluctuations via emergent temporal niches","volume":"20","author":"B Bloxham","year":"2024","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1013222.ref018","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.57790","article-title":"Nutrient levels and trade-offs control diversity in a serial dilution ecosystem","volume":"9","author":"A Erez","year":"2020","journal-title":"Elife."},{"key":"pcbi.1013222.ref019","unstructured":"Lotka AJ. Elements of physical biology. Williams & Wilkins; 1925."},{"issue":"1","key":"pcbi.1013222.ref020","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1093\/icesjms\/3.1.3","article-title":"Variations andfluctuations of the number of individuals in animal species living together","volume":"3","author":"V Volterra","year":"1928","journal-title":"ICES J Marine Sci."},{"issue":"6","key":"pcbi.1013222.ref021","article-title":"Deciphering microbial interactions in synthetic human gut microbiome communities","volume":"14","author":"OS Venturelli","year":"2018","journal-title":"MolSystBiol."},{"key":"pcbi.1013222.ref022","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.25051","article-title":"Lotka-Volterrapairwise modeling fails to capture diverse pairwise microbial interactions","volume":"6","author":"B Momeni","year":"2017","journal-title":"Elife."},{"issue":"6","key":"pcbi.1013222.ref023","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1073\/pnas.51.6.1207","article-title":"Competition, habitat selection, and character displacement in a patchy environment","volume":"51","author":"R Macarthur","year":"1964","journal-title":"ProcNatlAcadSciU S A."},{"issue":"1","key":"pcbi.1013222.ref024","first-page":"1","article-title":"Species packing and competitive equilibrium for many species","volume":"1","author":"R MacArthur","year":"1970","journal-title":"TheorPopulBiol."},{"issue":"1","key":"pcbi.1013222.ref025","first-page":"26","article-title":"MacArthur\u2019s consumer-resource model","volume":"37","author":"P Chesson","year":"1990","journal-title":"TheorPopulatBiol."},{"issue":"3","key":"pcbi.1013222.ref026","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1086\/283633","article-title":"Resources:a graphical-mechanistic approach to competition and predation","volume":"116","author":"D Tilman","year":"1980","journal-title":"AmNaturalist."},{"key":"pcbi.1013222.ref027","doi-asserted-by":"crossref","unstructured":"Tilman D. Resource competition and community structure. Princeton University Press; 1982.","DOI":"10.1515\/9780691209654"},{"key":"pcbi.1013222.ref028","first-page":"1","article-title":"Resource competition predicts assembly of gut bacterial communities in vitro","author":"PY Ho","year":"2024","journal-title":"NatMicrobiol."},{"key":"pcbi.1013222.ref029","first-page":"2024","article-title":"Fitness advantage of sequential metabolic strategies emerges from community interactions in strongly fluctuating environments","author":"Z Wang","year":"2024","journal-title":"bioRxiv"},{"issue":"5","key":"pcbi.1013222.ref030","article-title":"Diauxic lags explain unexpected coexistence in multi-resource environments","volume":"18","author":"B Bloxham","year":"2022","journal-title":"MolSystBiol."},{"issue":"1","key":"pcbi.1013222.ref031","first-page":"3510","article-title":"Culturing of a complex gut microbial community in mucin-hydrogel carriers reveals strain- and gene-associated spatial organization","volume":"14","author":"X Jin","year":"2023","journal-title":"NatCommun."},{"issue":"12","key":"pcbi.1013222.ref032","article-title":"Control points for design of taxonomic composition in synthetic human gut communities","volume":"14","author":"BM Connors","year":"2023","journal-title":"Cell Syst."},{"issue":"7867","key":"pcbi.1013222.ref033","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41586-021-03707-9","article-title":"A metabolomics pipeline for the mechanistic interrogation of the gut microbiome","volume":"595","author":"S Han","year":"2021","journal-title":"Nature."},{"issue":"1","key":"pcbi.1013222.ref034","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s40168-021-01059-0","article-title":"Identifying biases and their potential solutions in human microbiome studies","volume":"9","author":"JT Nearing","year":"2021","journal-title":"Microbiome."},{"issue":"5","key":"pcbi.1013222.ref035","article-title":"Dynamic metabolic adaptation can promote species coexistence in competitive microbialcommunities","volume":"16","author":"L Pacciani-Mori","year":"2020","journal-title":"PLoSComputBiol."},{"issue":"1","key":"pcbi.1013222.ref036","first-page":"55","article-title":"An RNA-centric view on gutBacteroidetes","volume":"402","author":"D Ryan","year":"2020","journal-title":"BiolChem."},{"issue":"6","key":"pcbi.1013222.ref037","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01824-17","article-title":"Differentsubstrate preferences help closely related bacteria to coexist in the gut","volume":"8","author":"P Louis","year":"2017","journal-title":"mBio."},{"issue":"12","key":"pcbi.1013222.ref038","article-title":"Evidence for a multi-level trophic organization of the human gut microbiome","volume":"15","author":"T Wang","year":"2019","journal-title":"PLoSComputBiol."},{"issue":"1","key":"pcbi.1013222.ref039","first-page":"1335","article-title":"Ecology-guided prediction of cross-feeding interactions in the human gut microbiome","volume":"12","author":"A Goyal","year":"2021","journal-title":"NatCommun."},{"key":"pcbi.1013222.ref040","doi-asserted-by":"crossref","first-page":"910377","DOI":"10.3389\/fpls.2022.910377","article-title":"Elucidatingplant-microbe-environment interactions through omics-enabled metabolic modelling using synthetic communities","volume":"13","author":"AE Beck","year":"2022","journal-title":"Front Plant Sci."},{"issue":"10","key":"pcbi.1013222.ref041","first-page":"1445","article-title":"Synthetic microbiota reveal priority effects and keystone strains in the Arabidopsisphyllosphere","volume":"3","author":"CI Carlstr\u00f6m","year":"2019","journal-title":"NatEcolEvol."},{"issue":"12","key":"pcbi.1013222.ref042","first-page":"731","article-title":"Reconstructing organisms insilico: genome-scale models and their emerging applications","volume":"18","author":"X Fang","year":"2020","journal-title":"Nat RevMicrobiol."},{"issue":"3","key":"pcbi.1013222.ref043","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2021.12.036","article-title":"Genomic structure predicts metabolite dynamics in microbial communities","volume":"185","author":"K Gowda","year":"2022","journal-title":"Cell."},{"issue":"10","key":"pcbi.1013222.ref044","first-page":"1799","article-title":"Genome content predicts the carbon catabolic preferences of heterotrophic bacteria","volume":"8","author":"M Gralka","year":"2023","journal-title":"NatMicrobiol."},{"issue":"2","key":"pcbi.1013222.ref045","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.02481-14","article-title":"Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of theproatherogenicmetabolite trimethylamine-N-oxide","volume":"6","author":"KA Romano","year":"2015","journal-title":"mBio."},{"key":"pcbi.1013222.ref046","doi-asserted-by":"crossref","unstructured":"Lawson CL, Hanson RJ. Solving least squares problems. SIAM; 1995.","DOI":"10.1137\/1.9781611971217"},{"issue":"3","key":"pcbi.1013222.ref047","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy1.0: fundamental algorithms for scientific computing in Python","volume":"17","author":"P Virtanen","year":"2020","journal-title":"Nat Methods."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1013222","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T17:57:24Z","timestamp":1752775044000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013222"}},"subtitle":[],"editor":[{"given":"Nic","family":"Vega","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,7,14]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1013222","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.01.23.576928","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,14]]}}}