{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:30:23Z","timestamp":1790314223638,"version":"4.1.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      As the predominant constituents of the vaginal microbiome in healthy women,\n                      <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                      species are considered essential in maintaining a homeostatic vaginal microbiome. Specific\n                      <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                      species can produce beneficial metabolites to support their persistence within the host environment and inhibit\n                      <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                      colonization. Due to the extensive diversity of\n                      <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                      species and their metabolites, comprehensively investigating all possible interactions remains challenging. This study employed an integrative approach combining genome-scale metabolic modeling, metagenomic sequencing, and\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      validation to explore\n                      <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      interactions. Pairwise simulations of 159\n                      <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                      strains with\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      revealed that most strains exhibit inhibitory effects, altering fungal amino acid and carbohydrate metabolism. Key inhibitory metabolites identified included formate, L-lactate, and L-malate. Metagenomic analysis of vaginal swabs from 20 vulvovaginal candidiasis (VVC) patients and 20 healthy women showed a correlation between\n                      <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                      species abundance and reduced\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      colonization.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      experiments confirmed the inhibitory effects of these metabolites and the selected\n                      <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                      strains on\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      growth, thereby validating our computational predictions. These findings provide insights into the metabolic interactions within the vaginal microbiome and pave the way for targeted microbial or metabolite-based therapeutic strategies to manage VVC.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Vulvovaginal candidiasis is a prevalent fungal infection with significant implications for women\u2019s health, caused primarily by\n                        <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                        . Although the protective role of a\n                        <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                        -dominated vaginal microbiome is well established, the metabolic mechanisms underlying the interactions between\n                        <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                        species and\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        remain inadequately understood. Specifically, the\n                        <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                        species that effectively inhibit\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        and the metabolic pathways involved warrant further investigation. This study offers novel insights into the metabolic mechanisms underlying\n                        <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                        antagonism against\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        . By identifying critical metabolic pathways and inhibitory metabolites, this study enhances our understanding of vaginal microbiome dynamics and host-microbe interactions. The findings suggest that key\n                        <jats:italic toggle=\"yes\">Lactobacillus<\/jats:italic>\n                        strains and their metabolites could significantly reduce harmful levels of\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        , paving the way for future therapeutic strategies that leverage these microbial characteristics to promote vaginal health.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02984-24","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T09:03:17Z","timestamp":1744794197000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Genome-scale metabolic modeling reveals specific vaginal\n                    <i>Lactobacillus<\/i>\n                    strains and their metabolites as key inhibitors of\n                    <i>Candida albicans<\/i>"],"prefix":"10.1128","volume":"13","author":[{"given":"Tianqi","family":"Hu","sequence":"first","affiliation":[{"name":"Microbiome-X, School of Public Health, Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Meng","sequence":"additional","affiliation":[{"name":"Microbiome-X, School of Public Health, Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Microbiome-X, School of Public Health, Cheeloo College of Medicine, Shandong University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dashuang","family":"Sheng","sequence":"additional","affiliation":[{"name":"Microbiome-X, School of Public Health, Cheeloo College of Medicine, Shandong 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