{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T18:07:06Z","timestamp":1783966026241,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of China","award":["32302922"],"award-info":[{"award-number":["32302922"]}]},{"name":"Natural Science Foundation of China","award":["2024J08038"],"award-info":[{"award-number":["2024J08038"]}]},{"name":"Natural Science Foundation of China","award":["JAT220060"],"award-info":[{"award-number":["JAT220060"]}]},{"name":"Natural Science foundation of Fujian province","award":["32302922"],"award-info":[{"award-number":["32302922"]}]},{"name":"Natural Science foundation of Fujian province","award":["2024J08038"],"award-info":[{"award-number":["2024J08038"]}]},{"name":"Natural Science foundation of Fujian province","award":["JAT220060"],"award-info":[{"award-number":["JAT220060"]}]},{"name":"Education Research Fund for Young Academic of Fujian Province","award":["32302922"],"award-info":[{"award-number":["32302922"]}]},{"name":"Education Research Fund for Young Academic of Fujian Province","award":["2024J08038"],"award-info":[{"award-number":["2024J08038"]}]},{"name":"Education Research Fund for Young Academic of Fujian Province","award":["JAT220060"],"award-info":[{"award-number":["JAT220060"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: The impact of heat stress on intestinal bacterial antimicrobial resistance (AMR) and its underlying mechanisms is not fully understood. This study aims to explore how heat stress influences AMR in the gut and the mechanisms involved. Methods: A Specific-Pathogen-Free (SPF) mouse model was used, divided into a control group (maintained at 25 \u00b0C) and a heat stress group (exposed to 42 \u00b0C for 30 min twice daily for 55 days). The effectiveness of the model was verified by RT-qPCR and histopathological analysis. Antibiotic susceptibility testing and clonal analysis (ERIC-PCR) were performed. Colonization assays were conducted to determine the accumulation of resistant strains in the gut. Metagenomic sequencing was conducted to investigated microbial composition. Results: RT-qPCR and Histopathological analysis revealed intestinal damage and significant upregulation of genes related to stress response, intestinal barrier integrity and inflammation, indicating successful model establishment and physiological alterations. Antibiotic susceptibility testing revealed increased resistance to erythromycin, chloramphenicol, and tetracycline among Enterococcus strains. Clonal analysis demonstrated that these resistant strains were clonally unrelated. Sequencing identified a novel ermB-carrying integrative and conjugative element (ICEFZMF) among four erythromycin-resistant strains. The rectum harbored a higher proportion of erythromycin-resistant Enterococcus strains with elevated minimum inhibitory concentrations (MICs) after 25 days of heat stress exposure. Colonization assays confirmed that heat stress led to the accumulation of erythromycin-resistant Enterococcus in the rectum. Metagenomic sequencing revealed significant changes in microbial composition, favoring anaerobic metabolism. Conclusions: This study suggests that chronic heat stress can promote the emergence of antibiotic-resistant strains through ICE transfer, providing insight for environmental safety.<\/jats:p>","DOI":"10.3390\/antibiotics14050460","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:44:58Z","timestamp":1746171898000},"page":"460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Chronic Heat Stress Can Induce Conjugation of a Novel ermB-Containing ICEFZMF, Increasing Resistance to Erythromycin Among Enterococcus Strains in Diverse Intestinal Segments in the Mouse Model"],"prefix":"10.3390","volume":"14","author":[{"given":"Lingxian","family":"Yi","sequence":"first","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zining","family":"Ren","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0084-6951","authenticated-orcid":false,"given":"Yu","family":"Feng","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yechun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianshuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihong","family":"Kuang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Deng","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yang","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daojin","family":"Yu","sequence":"additional","affiliation":[{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/jpn.12346","article-title":"Dietary supplementation with glutamine and gamma-aminobutyric acid improves growth performance and serum parameters in 22- to 35-day-old broilers exposed to hot environment","volume":"100","author":"Hu","year":"2016","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.mjafi.2014.04.011","article-title":"Antimicrobial resistance: A public health challenge","volume":"71","author":"Jindal","year":"2015","journal-title":"Med. J. Armed Forces India"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1146\/annurev-animal-111523-102133","article-title":"A One Health Approach to Reducing Livestock Disease Prevalence in Developing Countries: Advances, Challenges, and Prospects","volume":"13","author":"Lane","year":"2025","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Bava, R., Castagna, F., Lupia, C., Poerio, G., Liguori, G., Lombardi, R., Naturale, M.D., Mercuri, C., Bulotta, R.M., and Britti, D. (2024). Antimicrobial Resistance in Livestock: A Serious Threat to Public Health. Antibiotics, 13.","DOI":"10.3390\/antibiotics13060551"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ramos, S., Silva, V., Dapkevicius, M.L.E., Igrejas, G., and Poeta, P. (2020). Enterococci, from Harmless Bacteria to a Pathogen. Microorganisms, 8.","DOI":"10.20944\/preprints202007.0393.v1"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Torres, C., Alonso, C.A., Ruiz-Ripa, L., Leon-Sampedro, R., Del Campo, R., and Coque, T.M. (2018). Antimicrobial Resistance in Enterococcus spp. of animal origin. Microbiol. Spectr., 6.","DOI":"10.1128\/microbiolspec.ARBA-0032-2018"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Guan, L., Beig, M., Wang, L., Navidifar, T., Moradi, S., Motallebi Tabaei, F., Teymouri, Z., Abedi Moghadam, M., and Sedighi, M. (2024). Global status of antimicrobial resistance in clinical Enterococcus faecalis isolates: Systematic review and meta-analysis. Ann. Clin. Microbiol. Antimicrob., 23.","DOI":"10.1186\/s12941-024-00728-w"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3168\/jds.2018-14576","article-title":"Short communication: Antimicrobial resistance and virulence genes of Enterococcus faecalis isolated from subclinical bovine mastitis cases in China","volume":"102","author":"Yang","year":"2019","journal-title":"J. Dairy. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yi, L., Xu, R., Yuan, X., Ren, Z., Song, H., Lai, H., Sun, Z., Deng, H., Yang, B., and Yu, D. (2024). Heat stress enhances the occurrence of erythromycin resistance of Enterococcus isolates in mice feces. J. Therm. Biol., 120.","DOI":"10.1016\/j.jtherbio.2024.103786"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"110359","DOI":"10.1016\/j.foodres.2021.110359","article-title":"Effects of acid, alkaline, cold, and heat environmental stresses on the antibiotic resistance of the Salmonella enterica serovar Typhimurium","volume":"144","author":"Wu","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ijfoodmicro.2011.02.013","article-title":"Impact of environmental stress desiccation, acidity, alkalinity, heat or cold on antibiotic susceptibility of Cronobacter sakazakii","volume":"146","author":"Osaili","year":"2011","journal-title":"Int. J. Food Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4015","DOI":"10.1111\/j.1742-4658.2011.08305.x","article-title":"Induction of a stress response in Lactococcus lactis is associated with a resistance to ribosomally active antibiotics","volume":"278","author":"Dorrian","year":"2011","journal-title":"FEBS J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Rodriguez-Verdugo, A., Gaut, B.S., and Tenaillon, O. (2013). Evolution of Escherichia coli rifampicin resistance in an antibiotic-free environment during thermal stress. BMC Evol. Biol., 13.","DOI":"10.1186\/1471-2148-13-50"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/pbi.12659","article-title":"The heat-shock protein\/chaperone network and multiple stress resistance","volume":"15","author":"Jacob","year":"2017","journal-title":"Plant Biotechnol. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1016\/j.biocel.2012.04.002","article-title":"Small heat shock proteins HSP27 (HspB1), alphaB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death","volume":"44","author":"Acunzo","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.1007\/s10620-010-1558-x","article-title":"Evidence for enhanced cytoprotective function of HSP90-overexpressing small intestinal epithelial cells","volume":"56","author":"Tamaki","year":"2011","journal-title":"Dig. Dis. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1136\/vr.d4775","article-title":"Effects of transportation on expression of Hsp90, Hsp70, Hsp27 and alphaB-crystallin in the pig stomach","volume":"169","author":"Zhang","year":"2011","journal-title":"Vet. Rec."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tabler, T.W., Greene, E.S., Orlowski, S.K., Hiltz, J.Z., Anthony, N.B., and Dridi, S. (2020). Intestinal Barrier Integrity in Heat-Stressed Modern Broilers and Their Ancestor Wild Jungle Fowl. Front. Vet. Sci., 7.","DOI":"10.3389\/fvets.2020.00249"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, Y., Sun, W., Wu, E., Wang, K., Chen, X., Cui, Y., Zhang, G., Lv, F., Wang, Y., and Peng, X. (2022). Polysaccharides From Abrus cantoniensis Hance Modulate Intestinal Microflora and Improve Intestinal Mucosal Barrier and Liver Oxidative Damage Induced by Heat Stress. Front. Vet. Sci., 9.","DOI":"10.3389\/fvets.2022.868433"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1096\/fasebj.10.11.8836041","article-title":"Paneth cell defensins: Endogenous peptide components of intestinal host defense","volume":"10","author":"Ouellette","year":"1996","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"G422","DOI":"10.1152\/ajpgi.00412.2004","article-title":"Mechanism of TNF-alpha modulation of Caco-2 intestinal epithelial tight junction barrier: Role of myosin light-chain kinase protein expression","volume":"288","author":"Ma","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/j.1365-2982.2012.01921.x","article-title":"Intestinal barrier function in health and gastrointestinal disease","volume":"24","author":"Camilleri","year":"2012","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bischoff, S.C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.D., Serino, M., Tilg, H., Watson, A., and Wells, J.M. (2014). Intestinal permeability--a new target for disease prevention and therapy. BMC Gastroenterol., 14.","DOI":"10.1186\/s12876-014-0189-7"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pastorelli, L., De Salvo, C., Mercado, J.R., Vecchi, M., and Pizarro, T.T. (2013). Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: Lessons learned from animal models and human genetics. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00280"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.2527\/jas.2008-1624","article-title":"Heat-stress-induced damage to porcine small intestinal epithelium associated with downregulation of epithelial growth factor signaling","volume":"87","author":"Liu","year":"2009","journal-title":"J. Anim. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1053\/rvsc.2001.0448","article-title":"Thirty minutes transport causes small intestinal acidosis in pigs","volume":"70","author":"Nabuurs","year":"2001","journal-title":"Res. Vet. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.2174\/092986712800099767","article-title":"Radiation-induced stress proteins-the role of heat shock proteins (HSP) in anti- tumor responses","volume":"19","author":"Schmid","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yi, L., Durand, R., Grenier, F., Yang, J., Yu, K., Burrus, V., and Liu, J.H. (2022). PixR, a Novel Activator of Conjugative Transfer of IncX4 Resistance Plasmids, Mitigates the Fitness Cost of mcr-1 Carriage in Escherichia coli. mBio, 13.","DOI":"10.1128\/mbio.03209-21"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nrmicro884","article-title":"Genomic islands in pathogenic and environmental microorganisms","volume":"2","author":"Dobrindt","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/1574-6976.12067","article-title":"Bacterial insertion sequences: Their genomic impact and diversity","volume":"38","author":"Siguier","year":"2014","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.envint.2013.08.023","article-title":"Abundance and persistence of antibiotic resistance genes in livestock farms: A comprehensive investigation in eastern China","volume":"61","author":"Cheng","year":"2013","journal-title":"Environ. Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105222","DOI":"10.1016\/j.prevetmed.2020.105222","article-title":"Resistance patterns to C and D antibiotic categories for veterinary use of Campylobacter spp., Escherichia coli and Enterococcus spp. commensal isolates from laying hen farms in Spain during 2018","volume":"186","author":"Marin","year":"2021","journal-title":"Prev. Vet. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"125868","DOI":"10.1016\/j.jhazmat.2021.125868","article-title":"Short-term cold stress can reduce the abundance of antibiotic resistance genes in the cecum and feces in a pig model","volume":"416","author":"Yang","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_34","first-page":"14","article-title":"Interaction between the gut microbiome and mucosal immune system","volume":"4","author":"Shi","year":"2017","journal-title":"Mil. Med. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.chom.2014.02.005","article-title":"The treatment-naive microbiome in new-onset Crohn\u2019s disease","volume":"15","author":"Gevers","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1128\/jb.125.1.19-24.1976","article-title":"Microcalorimetric study of the anaerobic growth of Escherichia coli: Measurements of the affinity of whole cells for various energy substrates","volume":"125","author":"Belaich","year":"1976","journal-title":"J. Bacteriol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1017\/S1751731111002448","article-title":"Adaptation to hot climate and strategies to alleviate heat stress in livestock production","volume":"6","author":"Renaudeau","year":"2012","journal-title":"Animal"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.envsci.2013.01.019","article-title":"Seasonal alpine grazing trends in Switzerland: Economic importance and impact on biotic communities","volume":"32","author":"Flury","year":"2013","journal-title":"Environ. Sci. Policy"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"RP97144","DOI":"10.7554\/eLife.97144","article-title":"Enteric glia regulate Paneth cell secretion and intestinal microbial ecology","volume":"13","author":"Prochera","year":"2025","journal-title":"eLife"},{"key":"ref_40","unstructured":"CLSI (2022). CLSI. Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [32nd ed.]. CLSI supplement M100."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1080\/03079457.2017.1359404","article-title":"Characterization of Enterococcus faecalis isolates by chicken embryo lethality assay and ERIC-PCR","volume":"47","author":"Blanco","year":"2018","journal-title":"Avian Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1146\/annurev.genom.9.081307.164359","article-title":"Next-generation DNA sequencing methods","volume":"9","author":"Mardis","year":"2008","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1101\/gr.097261.109","article-title":"De novo assembly of human genomes with massively parallel short read sequencing","volume":"20","author":"Li","year":"2010","journal-title":"Genome Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1093\/bioinformatics\/btr039","article-title":"Easyfig: A genome comparison visualizer","volume":"27","author":"Sullivan","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chen, L., Huang, J., Huang, X., He, Y., Sun, J., Dai, X., Wang, X., Shafiq, M., and Wang, L. (2021). Horizontal Transfer of Different erm(B)-Carrying Mobile Elements Among Streptococcus suis Strains with Different Serotypes. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.628740"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"577048","DOI":"10.1016\/j.jneuroim.2019.577048","article-title":"An antibiotic depleted microbiome drives severe Campylobacter jejuni-mediated Type 1\/17 colitis, Type 2 autoimmunity and neurologic sequelae in a mouse model","volume":"337","author":"Brooks","year":"2019","journal-title":"J. Neuroimmunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1093\/bioinformatics\/btv033","article-title":"MEGAHIT: An ultra-fast single-node solution for large and complex metagenomics assembly via succinct de Bruijn graph","volume":"31","author":"Li","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ymeth.2016.02.020","article-title":"MEGAHIT v1.0: A fast and scalable metagenome assembler driven by advanced methodologies and community practices","volume":"102","author":"Li","year":"2016","journal-title":"Methods"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zeller, G., Tap, J., Voigt, A.Y., Sunagawa, S., Kultima, J.R., Costea, P.I., Amiot, A., Bohm, J., Brunetti, F., and Habermann, N. (2014). Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol. Syst. Biol., 10.","DOI":"10.15252\/msb.20145645"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"D354","DOI":"10.1093\/nar\/gkj102","article-title":"From genomics to chemical genomics: New developments in KEGG","volume":"34","author":"Kanehisa","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D199","DOI":"10.1093\/nar\/gkt1076","article-title":"Data, information, knowledge and principle: Back to metabolism in KEGG","volume":"42","author":"Kanehisa","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D443","DOI":"10.1093\/nar\/gkn656","article-title":"ARDB--Antibiotic Resistance Genes Database","volume":"37","author":"Liu","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1007\/s00784-023-04882-x","article-title":"Amplicon-based next-generation sequencing for comparative analysis of root canal microbiome of teeth with primary and persistent\/secondary endodontic infections","volume":"27","author":"Kesim","year":"2023","journal-title":"Clin. Oral. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W.S., and Huttenhower, C. (2011). Metagenomic biomarker discovery and explanation. Genome Biol., 12.","DOI":"10.1186\/gb-2011-12-6-r60"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"White, J.R., Nagarajan, N., and Pop, M. (2009). Statistical methods for detecting differentially abundant features in clinical metagenomic samples. PLoS Comput. Biol., 5.","DOI":"10.1371\/journal.pcbi.1000352"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/5\/460\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:25:31Z","timestamp":1760030731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/5\/460"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":58,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["antibiotics14050460"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14050460","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,30]]}}}