{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:55:08Z","timestamp":1780494908344,"version":"3.54.1"},"reference-count":62,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Texas Tech University School of Veterinary Medicine (TTU-SVM)","award":["6040-32000-011-05J"],"award-info":[{"award-number":["6040-32000-011-05J"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Salmonella Kentucky comprises two major lineages, ST152 and fluoroquinolone-resistant (FluR) ST198, which have diverged genotypically and phenotypically along distinct evolutionary and epidemiological trajectories. ST198 is linked to global human disease, while ST152 is primarily animal-associated in the U.S. We hypothesized that lineage-specific metabolic adaptations contribute to their differing host associations and pathogenicity. Methods: We performed comparative metabolic profiling of ST198 (n = 3) and ST152 (n = 4) strains across 948 substrates and environmental conditions. Growth assays tested the ability of these lineages and other non-typhoidal Salmonella (NTS) serovars (n = 5) to utilize myo-inositol and lactulose as sole carbon sources. Comparative genomic analyses of 294 ST198, 173 ST152, and 1300 other NTS serovars identified nutrient utilization genes. Results: ST198 exhibited significantly higher respiratory activity and broader metabolic versatility across carbon, nitrogen\/sulfur sources, and stress conditions. The canonical iol gene cluster for myo-inositol catabolism was conserved in ST198 but absent in ST152, which nonetheless showed weak growth on myo-inositol, suggesting an alternative metabolic pathway for myo-inositol may exist. We also report for the first time that, despite lineage-specific differences in metabolic efficiency, multiple NTS serovars, including S. Kentucky, can metabolize lactulose, a synthetic disaccharide traditionally associated with beneficial gut microbes. These results suggest the potential existence of a novel lactulose metabolic pathway in NTS. Conclusions: These findings highlight ST198\u2019s metabolic adaptability and reveal novel metabolic capacities in NTS. A mechanistic understanding of nutrient utilization pathways, particularly of myo-inositol and lactulose, will provide novel insights into the mechanisms underlying nutrient metabolism that likely modulate the ecological success and pathogenic potential of NTS in human and animal hosts.<\/jats:p>","DOI":"10.3390\/genes16091051","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T11:51:12Z","timestamp":1757332272000},"page":"1051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative Genomics and Functional Profiling Reveal Lineage-Specific Metabolic Adaptations in Globally Emerging Fluoroquinolone-Resistant Salmonella Kentucky ST198"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3904-9381","authenticated-orcid":false,"given":"Juned","family":"Ahmed","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-3597","authenticated-orcid":false,"given":"Rachel C.","family":"Soltys","sequence":"additional","affiliation":[{"name":"Animal Disease Diagnostic Laboratory, Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9212-9175","authenticated-orcid":false,"given":"Smriti","family":"Shringi","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3968-4705","authenticated-orcid":false,"given":"Jean","family":"Guard","sequence":"additional","affiliation":[{"name":"United States National Poultry Research Center, Agriculture Research Service, United States Department of Agriculture, Athens, GA 30605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7996-1143","authenticated-orcid":false,"given":"Bradd J.","family":"Haley","sequence":"additional","affiliation":[{"name":"Environmental Microbial and Food Safety Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, MD 20705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6365-7868","authenticated-orcid":false,"given":"Devendra H.","family":"Shah","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine, Texas Tech University, Amarillo, TX 79106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1086\/650733","article-title":"The Global Burden of Nontyphoidal Salmonella Gastroenteritis","volume":"50","author":"Majowicz","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/zph.12571","article-title":"Salmonella Enterica Serovar Kentucky Recovered from Human Clinical Cases in Maryland, USA (2011\u20132015)","volume":"66","author":"Haley","year":"2019","journal-title":"Zoonoses Public Health"},{"key":"ref_3","first-page":"001089","article-title":"Genomic and Phenotypic Characterization of Salmonella Enterica Serovar Kentucky","volume":"9","author":"Richards","year":"2023","journal-title":"Microb. Genom."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1089\/fpd.2022.0005","article-title":"Genomic Diversity, Antimicrobial Resistance, and Virulence Gene Profiles of Salmonella Serovar Kentucky Isolated from Humans, Food, and Animal Ceca Content Sources in the United States","volume":"19","author":"Tate","year":"2022","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_5","first-page":"000877","article-title":"Epidemiological Links and Antimicrobial Resistance of Clinical Salmonella Enterica ST198 Isolates: A Nationwide Microbial Population Genomic Study in Switzerland","volume":"8","author":"Biggel","year":"2022","journal-title":"Microb. Genom."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/S1473-3099(13)70124-5","article-title":"Highly Drug-Resistant Salmonella Enterica Serotype Kentucky ST198-X1: A Microbiological Study","volume":"13","author":"Hello","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s44259-023-00003-6","article-title":"Highly Drug Resistant Clone of Salmonella Kentucky ST198 in Clinical Infections and Poultry in Zimbabwe","volume":"1","author":"Mashe","year":"2023","journal-title":"Npj Antimicrob. Resist."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/zph.12884","article-title":"Genomic Diversity and Resistome Profiles of Salmonella Enterica Subsp. Enterica Serovar Kentucky Isolated from Food and Animal Sources in Ireland","volume":"69","author":"Slowey","year":"2022","journal-title":"Zoonoses Public Health"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Soltys, R.C., Sakomoto, C.K., Oltean, H.N., Guard, J., Haley, B.J., and Shah, D.H. (2021). High-Resolution Comparative Genomics of Salmonella Kentucky Aids Source Tracing and Detection of ST198 and ST152 Lineage-Specific Mutations. Front. Sustain. Food Syst., 5.","DOI":"10.3389\/fsufs.2021.695368"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Haley, B.J., Kim, S.W., Pettengill, J., Luo, Y., Karns, J.S., and Kessel, J.A.S.V. (2016). Genomic and Evolutionary Analysis of Two Salmonella Enterica Serovar Kentucky Sequence Types Isolated from Bovine and Poultry Sources in North America. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161225"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00944-23","DOI":"10.1128\/aem.00944-23","article-title":"Poultry Production as the Main Reservoir of Ciprofloxacin- and Tigecycline-Resistant Extended-Spectrum \u03b2-Lactamase (ESBL)-Producing Salmonella Enterica Serovar Kentucky ST198.2-2 Causing Human Infections in China","volume":"89","author":"Wang","year":"2023","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e00935-20","DOI":"10.1128\/mSystems.00935-20","article-title":"National Prevalence of Salmonella Enterica Serotype Kentucky ST198 with High-Level Resistance to Ciprofloxacin and Extended-Spectrum Cephalosporins in China, 2013 to 2017","volume":"6","author":"Chen","year":"2021","journal-title":"mSystems"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez, X., Fern\u00e1ndez, J., Bances, M., Lumbreras, P., Alkorta, M., Hern\u00e1ez, S., Prieto, E., de la Iglesia, P., de Toro, M., and Rodicio, M.R. (2021). Genomic Analysis of Ciprofloxacin-Resistant Salmonella Enterica Serovar Kentucky ST198 From Spanish Hospitals. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.720449"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wo\u0142kowicz, T., Zacharczuk, K., Gierczy\u0144ski, R., Nowakowska, M., and Piekarska, K. (2021). Antimicrobial Resistance and Whole-Genome Characterisation of High-Level Ciprofloxacin-Resistant Salmonella Enterica Serovar Kentucky ST 198 Strains Isolated from Human in Poland. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179381"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e00125-18","DOI":"10.1128\/genomeA.00125-18","article-title":"Complete Genome Sequence of a Ciprofloxacin-Resistant Salmonella Enterica Subsp. Enterica Serovar Kentucky Sequence Type 198 Strain, PU131, Isolated from a Human Patient in Washington State","volume":"6","author":"Shah","year":"2018","journal-title":"Genome Announc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1111\/zph.13075","article-title":"Ciprofloxacin-Resistant ST198 Salmonella Kentucky in a Hospitalized American Black Bear (Ursus americanus), with Evidence of Subsequent Nosocomial Transmission","volume":"70","author":"Cummings","year":"2023","journal-title":"Zoonoses Public Health"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Okoro, C.K., Barquist, L., Connor, T.R., Harris, S.R., Clare, S., Stevens, M.P., Arends, M.J., Hale, C., Kane, L., and Pickard, D.J. (2015). Signatures of Adaptation in Human Invasive Salmonella Typhimurium ST313 Populations from Sub-Saharan Africa. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003848"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s44259-024-00027-6","article-title":"Population Structure and Ongoing Microevolution of the Emerging Multidrug-Resistant Salmonella Typhimurium ST213","volume":"2","author":"Calva","year":"2024","journal-title":"Npj Antimicrob. Resist."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.tim.2018.06.001","article-title":"Evolution of Salmonella within Hosts","volume":"26","author":"Tanner","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Burin, R., and Shah, D.H. (2021). Phenelzine and Amoxapine Inhibit Tyramine and D-Glucuronic Acid Catabolism in Clinically Significant Salmonella in A Serotype-Independent Manner. Pathogens, 10.","DOI":"10.3390\/pathogens10040469"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7857","DOI":"10.1128\/AEM.03040-13","article-title":"Dimethyl Adenosine Transferase (KsgA) Deficiency in Salmonella Enterica Serovar Enteritidis Confers Susceptibility to High Osmolarity and Virulence Attenuation in Chickens","volume":"79","author":"Chiok","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.ijmm.2018.10.004","article-title":"Genomic Organization and Role of SPI-13 in Nutritional Fitness of Salmonella","volume":"308","author":"Elder","year":"2018","journal-title":"Int. J. Med. Microbiol. IJMM"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7753","DOI":"10.1128\/AEM.01228-07","article-title":"Detection of Salmonella Enterica Subpopulations by Phenotype Microarray Antibiotic Resistance Patterns","volume":"73","author":"Morales","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_24","unstructured":"Kolde, R. (2025, August 26). Pheatmap: Pretty Heatmaps. R Package, version 1.0.12. Available online: https:\/\/CRAN.R-project.org\/package=pheatmap."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4412","DOI":"10.1093\/bioinformatics\/btac504","article-title":"PanExplorer: A Web-Based Tool for Exploratory Analysis and Visualization of Bacterial Pan-Genomes","volume":"38","author":"Dereeper","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kr\u00f6ger, C., Rothhardt, J.E., Brokatzky, D., Felsl, A., Kary, S.C., Heermann, R., and Fuchs, T.M. (2018). The Small RNA RssR Regulates Myo-Inositol Degradation by Salmonella Enterica. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-35784-8"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e02013-22","DOI":"10.1128\/spectrum.02013-22","article-title":"Metabolism in the Niche: A Large-Scale Genome-Based Survey Reveals Inositol Utilization To Be Widespread among Soil, Commensal, and Pathogenic Bacteria","volume":"10","author":"Weber","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1093\/molbev\/mst025","article-title":"Detecting Sequence Homology at the Gene Cluster Level with MultiGeneBlast","volume":"30","author":"Medema","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D678","DOI":"10.1093\/nar\/gkac1003","article-title":"Introducing the Bacterial and Viral Bioinformatics Resource Center (BV-BRC): A Resource Combining PATRIC, IRD and ViPR","volume":"51","author":"Olson","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6781","DOI":"10.1002\/jsfa.14389","article-title":"A Novel \u03b2-Galactosidase from Anaerobic Thermophilic Caldicellulosiruptor Saccharolyticus DSM 8903 with High Potential for Lactulose Production","volume":"105","author":"Baramee","year":"2025","journal-title":"J. Sci. Food Agric."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kumari, S., Panesar, P.S., Panwar, D., and Singla, G. (2022). Lactulose. Probiotics, Prebiotics and Synbiotics, John Wiley & Sons, Ltd.","DOI":"10.1002\/9781119702160.ch14"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10970","DOI":"10.1021\/jf503484d","article-title":"In Vitro Fermentation of Lactulose by Human Gut Bacteria","volume":"62","author":"Mao","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1099\/00221287-128-2-319","article-title":"The Fermentation of Lactulose by Colonic Bacteria","volume":"128","author":"Sahota","year":"1982","journal-title":"Microbiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1007\/s13197-024-05997-z","article-title":"Review of History and Mechanisms of Action of Lactulose (4-O-\u03b2-D-Galactopyranosyl-\u03b2-D-Fructofuranose): Present and Future Applications in Food","volume":"61","year":"2024","journal-title":"J. Food Sci. Technol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Aung, K.T., Khor, W.C., Ong, K.H., Tan, W.L., Wong, Z.N., Oh, J.Q., Wong, W.K., Tan, B.Z.Y., Maiwald, M., and Tee, N.W.S. (2022). Characterisation of Salmonella Enteritidis ST11 and ST1925 Associated with Human Intestinal and Extra-Intestinal Infections in Singapore. Int. J. Environ. Res. Public Health, 19.","DOI":"10.3390\/ijerph19095671"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41564-020-00836-1","article-title":"Stepwise Evolution of Salmonella Typhimurium ST313 Causing Bloodstream Infection in Africa","volume":"6","author":"Pulford","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00920-24","DOI":"10.1128\/aem.00920-24","article-title":"Osmotic Stress Response of the Coral and Oyster Pathogen Vibrio Coralliilyticus: Acquisition of Catabolism Gene Clusters for the Compatible Solute and Signaling Molecule Myo-Inositol","volume":"90","author":"Loughran","year":"2024","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5000","DOI":"10.1128\/AEM.01018-16","article-title":"Metabolism of Myo-Inositol by Legionella Pneumophila Promotes Infection of Amoebae and Macrophages","volume":"82","author":"Manske","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e02724-23","DOI":"10.1128\/spectrum.02724-23","article-title":"Hierarchic Regulation of a Metabolic Pathway: H-NS, CRP, and SsrB Control Myo-Inositol Utilization by Salmonella Enterica","volume":"12","author":"Felsl","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/mmi.12788","article-title":"The Orphan Regulator ReiD of Salmonella Enterica Is Essential for Myo-Inositol Utilization","volume":"94","author":"Rothhardt","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1099\/mic.0.032250-0","article-title":"Myo-Inositol Transport by Salmonella Enterica Serovar Typhimurium","volume":"156","author":"Stolz","year":"2010","journal-title":"Microbiology"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Chhetri, D.R. (2019). Myo-Inositol and Its Derivatives: Their Emerging Role in the Treatment of Human Diseases. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01172"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1016\/j.biochi.2013.05.011","article-title":"Potential Role and Therapeutic Interests of Myo-Inositol in Metabolic Diseases","volume":"95","author":"Croze","year":"2013","journal-title":"Biochimie"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1080\/09637486.2020.1852191","article-title":"Myo-Inositol Supplementation to Prevent Gestational Diabetes in Overweight Non-Obese Women: Bioelectrical Impedance Analysis, Metabolic Aspects, Obstetric and Neonatal Outcomes\u2014A Randomized and Open-Label, Placebo-Controlled Clinical Trial","volume":"72","author":"Vitale","year":"2021","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Reddy, N.R., and Sathe, S.K. (2001). Food Phytates, CRC Press. [1st ed.].","DOI":"10.1201\/9781420014419"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"S330","DOI":"10.1002\/mnfr.200900099","article-title":"Phytate in Foods and Significance for Humans: Food Sources, Intake, Processing, Bioavailability, Protective Role and Analysis","volume":"53","author":"Schlemmer","year":"2009","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1158\/1055-9965.EPI-06-0128","article-title":"A Phase I Study of Myo-Inositol for Lung Cancer Chemoprevention","volume":"15","author":"Lam","year":"2006","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9537632","DOI":"10.1155\/2016\/9537632","article-title":"Myoinositol as a Safe and Alternative Approach in the Treatment of Infertile PCOS Women: A German Observational Study","volume":"2016","author":"Regidor","year":"2016","journal-title":"Int. J. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"14057","DOI":"10.1073\/pnas.95.24.14057","article-title":"SopB, a Protein Required for Virulence of Salmonella Dublin, Is an Inositol Phosphate Phosphatase","volume":"95","author":"Norris","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1046\/j.1365-2958.2001.02230.x","article-title":"A Salmonella Inositol Polyphosphatase Acts in Conjunction with Other Bacterial Effectors to Promote Host Cell Actin Cytoskeleton Rearrangements and Bacterial Internalization","volume":"39","author":"Zhou","year":"2001","journal-title":"Mol. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Berlemont, R., and Martiny, A.C. (2016). Glycoside Hydrolases across Environmental Microbial Communities. PLoS Comput. Biol., 12.","DOI":"10.1371\/journal.pcbi.1005300"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"El Mouali, Y., Gaviria-Cantin, T., S\u00e1nchez-Romero, M.A., Gibert, M., Westermann, A.J., Vogel, J., and Balsalobre, C. (2018). CRP-cAMP Mediates Silencing of Salmonella Virulence at the Post-Transcriptional Level. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007401"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1111\/mmi.12149","article-title":"The Intestinal Fatty Acid Propionate Inhibits Salmonella Invasion through the Post-Translational Control of HilD","volume":"87","author":"Hung","year":"2013","journal-title":"Mol. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D490","DOI":"10.1093\/nar\/gkt1178","article-title":"The Carbohydrate-Active Enzymes Database (CAZy) in 2013","volume":"42","author":"Lombard","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Karakan, T., Tuohy, K.M., and Janssen-van Solingen, G. (2021). Low-Dose Lactulose as a Prebiotic for Improved Gut Health and Enhanced Mineral Absorption. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.672925"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hecht, A.L., Mahmud, N., Chaudhry, S., Cao, J.Y., Branigan, G.P., Lee, J., Theiller, E., Roggiani, M., Friedman, E.S., and Herman, L. (2025). Carbohydrate Consumption Drives Adaptive Mutations in Escherichia Coli Associated with Increased Risk for Systemic Infection. BioRxiv.","DOI":"10.1101\/2025.03.26.645536"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1136\/gut.52.11.1572","article-title":"van der Dietary Fructo-Oligosaccharides and Lactulose Inhibit Intestinal Colonisation but Stimulate Translocation of Salmonella in Rats","volume":"52","author":"Meer","year":"2003","journal-title":"Gut"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wotzka, S.Y., Kreuzer, M., Maier, L., Z\u00fcnd, M., Schlumberger, M., Nguyen, B., Fox, M., Pohl, D., Heinrich, H., and Rogler, G. (2018). Microbiota Stability in Healthy Individuals after Single-Dose Lactulose Challenge\u2014A Randomized Controlled Study. PLoS ONE, 13.","DOI":"10.1101\/424531"},{"key":"ref_59","first-page":"43","article-title":"Effect of Lactulose on the Composition and Metabolic Activity of the Human Faecal Flora","volume":"5","author":"Terada","year":"1992","journal-title":"Microb. Ecol. Health Dis."},{"key":"ref_60","first-page":"165","article-title":"A Human Volunteer Study to Determine the Prebiotic Effects of Lactulose Powder on Human Colonic Microbiota","volume":"14","author":"Tuohy","year":"2002","journal-title":"Microb. Ecol. Health Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"90","DOI":"10.17221\/8722-VETMED","article-title":"Effects of Lactulose on Growth, Carcass Characteristics, Faecal Microbiota, and Blood Constituents in Broilers","volume":"61","author":"Nyachoti","year":"2016","journal-title":"Veterin\u00e1rn\u00ed Medic\u00edna"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.vetmic.2009.09.061","article-title":"Evaluation of the Inclusion of a Mixture of Organic Acids or Lactulose into the Feed of Pigs Experimentally Challenged with Salmonella Typhimurium","volume":"142","author":"Costabile","year":"2010","journal-title":"Vet. Microbiol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/9\/1051\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:41:57Z","timestamp":1760035317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/9\/1051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":62,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["genes16091051"],"URL":"https:\/\/doi.org\/10.3390\/genes16091051","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,8]]}}}