{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T09:04:33Z","timestamp":1774343073936,"version":"3.50.1"},"reference-count":73,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nordic Alumni Engagement Initiative 2026"},{"DOI":"10.13039\/501100005621","name":"Kasetsart University Research and Development Institute","doi-asserted-by":"crossref","award":["FF(KU)29.67"],"award-info":[{"award-number":["FF(KU)29.67"]}],"id":[{"id":"10.13039\/501100005621","id-type":"DOI","asserted-by":"crossref"}]},{"name":"KUSynBio Special Research Incubator Unit","award":["FF(KU-SRIU)5.69"],"award-info":[{"award-number":["FF(KU-SRIU)5.69"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Fermentation"],"abstract":"<jats:p>Limosilactobacillus fermentum KUB-D18 is a probiotic strain with significant potential in food fermentation and health promotion, yet the systems-level mechanisms underlying its physiological robustness remain elusive. To elucidate the metabolic remodeling strategies operating across growth phases, we developed an integrated framework combining genome-scale metabolic modeling (GSMM) with transcriptomics. A high-quality metabolic model for L. fermentum KUB-D18, designated iYH640 and comprising 640 genes, 1530 metabolites, and 1922 reactions, was constructed and validated against experimental growth data. Specifically, in vitro assays measuring biomass and glucose concentrations showed a maximum specific growth rate of 0.2696 h\u22121 and a glucose uptake rate of 11.75 mmol gDCW\u22121 h\u22121, providing physiological constraints for the model. Using transcriptome-regulated flux balance analysis (TR-FBA), gene expression profiles from the logarithmic phase (L-phase) and stationary phase (S-phase) were integrated to quantify growth phase-specific metabolic flux distributions. These simulations revealed a distinct transcription-driven metabolic shift, in which the organism moves from a proliferation-oriented metabolic state with active central carbon metabolism and macromolecule synthesis to a maintenance-oriented state. This S-phase is characterized by reduced flux through anabolic pathways together with the selective preservation of redox balance and nucleotide homeostasis. Collectively, these results provide a quantitative explanation of how L. fermentum KUB-D18 balances growth and maintenance, offering a mechanistic basis for improving its stability and functional performance in industrial probiotic applications.<\/jats:p>","DOI":"10.3390\/fermentation12030168","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T08:47:42Z","timestamp":1774255662000},"page":"168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Growth Physiology and Transcriptome Profiling Uncover Probiotic Adaptability of Limosilactobacillus fermentum KUB-D18"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3043-0493","authenticated-orcid":false,"given":"Yuke","family":"He","sequence":"first","affiliation":[{"name":"Interdisciplinary Graduate Program in Bioscience, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"}]},{"given":"Suttavadee","family":"Junyakul","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4442-3411","authenticated-orcid":false,"given":"Nachon","family":"Raethong","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1277-9299","authenticated-orcid":false,"given":"Massalin","family":"Nakphaichit","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok 10900, Thailand"},{"name":"Center of Excellence for Microbiota Innovation, Kasetsart University, Bangkok 10900, Thailand"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-6198","authenticated-orcid":false,"given":"Solange I.","family":"Mussatto","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Biomedicine, Technical University of Denmark, S\u00f8ltofts Plads, Building 223, 2800 Kongens Lyngby, Denmark"}]},{"given":"Wanwipa","family":"Vongsangnak","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand"},{"name":"Omics Center for Agriculture, Bioresources, Food, and Health, Kasetsart University (OmiKU), Bangkok 10900, Thailand"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"146747","DOI":"10.1016\/j.gene.2022.146747","article-title":"Comparative genomics-based probiotic relevance of Limosilactobacillus fermentum KUB-D18","volume":"840","author":"Phujumpa","year":"2022","journal-title":"Gene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1177\/10820132211012252","article-title":"Selection of potential probiotics with cholesterol-lowering properties for probiotic yoghurt production","volume":"28","author":"Wongrattanapipat","year":"2022","journal-title":"Food Sci. 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