{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:17Z","timestamp":1787029037064,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Apigenin is a major dietary flavonoid with many bioactivities, widely distributed in plants. Apigenin reaches the colon region intact and interacts there with the human gut microbiota, however there is little research on how apigenin affects the gut bacteria. This study investigated the effect of pure apigenin on human gut bacteria, at both the single strain and community levels. The effect of apigenin on the single gut bacteria strains Bacteroides galacturonicus, Bifidobacterium catenulatum, Lactobacillus rhamnosus GG, and Enterococcus caccae, was examined by measuring their anaerobic growth profiles. The effect of apigenin on a gut microbiota community was studied by culturing a fecal inoculum under in vitro conditions simulating the human ascending colon. 16S rRNA gene sequencing and GC-MS analysis quantified changes in the community structure. Single molecule RNA sequencing was used to reveal the response of Enterococcus caccae to apigenin. Enterococcus caccae was effectively inhibited by apigenin when cultured alone, however, the genus Enterococcus was enhanced when tested in a community setting. Single molecule RNA sequencing found that Enterococcus caccae responded to apigenin by up-regulating genes involved in DNA repair, stress response, cell wall synthesis, and protein folding. Taken together, these results demonstrate that apigenin affects both the growth and gene expression of Enterococcus caccae.<\/jats:p>","DOI":"10.3390\/molecules22081292","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T09:47:19Z","timestamp":1501753639000},"page":"1292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Apigenin Impacts the Growth of the Gut Microbiota and Alters the Gene Expression of Enterococcus"],"prefix":"10.3390","volume":"22","author":[{"given":"Minqian","family":"Wang","sequence":"first","affiliation":[{"name":"Dairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, US Department of Agriculture, 600 E Mermaid Lane, Wyndmoor, PA 19038, USA"},{"name":"Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenni","family":"Firrman","sequence":"additional","affiliation":[{"name":"Dairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, US Department of Agriculture, 600 E Mermaid Lane, Wyndmoor, PA 19038, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Virginia Tech, 114 MCB Hall, Blacksburg, VA 24060, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Arango-Argoty","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Virginia Tech, 114 MCB Hall, Blacksburg, VA 24060, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4059-7804","authenticated-orcid":false,"given":"Peggy","family":"Tomasula","sequence":"additional","affiliation":[{"name":"Dairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, US Department of Agriculture, 600 E Mermaid Lane, Wyndmoor, PA 19038, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3962-290X","authenticated-orcid":false,"given":"LinShu","family":"Liu","sequence":"additional","affiliation":[{"name":"Dairy and Functional Foods Research Unit, Eastern Regional Research Center, Agricultural Research Service, US Department of Agriculture, 600 E Mermaid Lane, Wyndmoor, PA 19038, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kit","family":"Yam","sequence":"additional","affiliation":[{"name":"Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,3]]},"reference":[{"key":"ref_1","unstructured":"Bhagwat, S., Haytowitz, D.B., and Holden, J.M. (2017, July 10). USDA Database for the Flavonoid Content of Selected Foods Release 3.1, Available online: https:\/\/www.ars.usda.gov\/ARSUserFiles\/80400525\/Data\/Flav\/Flav_R03-1.pdf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.taap.2007.09.013","article-title":"Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K\/Akt pathway and \u03b24 integrin function in MDA-MB-231 breast cancer cells","volume":"226","author":"Lee","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0891-5849(98)00020-3","article-title":"Quercetin glucosides interact with the intestinal glucose transport pathway","volume":"25","author":"Gee","year":"1998","journal-title":"Free Radic. Biol. Med."},{"key":"ref_4","unstructured":"Janssen, K. (1997). Dietary Non-Nutrients and Haemostasis in Humans: Effects of Salicylates, Flavonoids and Ginger, Ponsen & Looijen."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s11130-007-0047-7","article-title":"Estimation of daily human intake of food flavonoids","volume":"62","author":"Mullie","year":"2007","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S0378-8741(00)00265-8","article-title":"Phytochemical flavones isolated from Scutellaria barbata and antibacterial activity against methicillin-resistant Staphylococcus aureus","volume":"72","author":"Sato","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/S0367-326X(00)00185-4","article-title":"Antibacterial and allelopathic activity of extract from Castanea sativa leaves","volume":"71","author":"Basile","year":"2000","journal-title":"Fitoterapia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/175851","article-title":"Antibacterial attributes of apigenin, isolated from Portulaca oleracea L.","volume":"2014","author":"Nayaka","year":"2014","journal-title":"Int. J. Bacteriol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/ptr.2061","article-title":"Antibacterial activity of flavonoids and phenylpropanoids from Marrubium globosum ssp. libanoticum","volume":"21","author":"Rigano","year":"2007","journal-title":"Phytother. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jep.2004.02.030","article-title":"Biological activity of five antibacterial flavonoids from Combretum erythrophyllum (Combretaceae)","volume":"93","author":"Martini","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1016\/j.bmcl.2007.01.032","article-title":"Validate antibacterial mode and find main bioactive components of traditional Chinese medicine Aquilegia oxysepala","volume":"17","author":"Yu","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_12","first-page":"233","article-title":"Apigenin and cancer chemoprevention: Progress, potential and promise (Review)","volume":"30","author":"Patel","year":"2007","journal-title":"Int. J. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7121","DOI":"10.4049\/jimmunol.179.10.7121","article-title":"Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-\u03baB through the suppression of p65 phosphorylation","volume":"179","author":"Nicholas","year":"2007","journal-title":"J. Immunol."},{"key":"ref_14","first-page":"104","article-title":"Study of antioxidant effect of apigenin, luteolin and quercetin by DNA protective method","volume":"48","author":"Rauko","year":"2001","journal-title":"Neoplasma"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1007\/s11095-010-0089-7","article-title":"Apigenin: A promising molecule for cancer prevention","volume":"27","author":"Shukla","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.jnutbio.2013.05.001","article-title":"Benefits of polyphenols on gut microbiota and implications in human health","volume":"24","author":"Cardona","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1021\/jf062088r","article-title":"Absorption and excretion of luteolin and apigenin in rats after oral administration of Chrysanthemum morifolium extract","volume":"55","author":"Chen","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1124\/dmd.104.000893","article-title":"Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration","volume":"33","author":"Gradolatto","year":"2005","journal-title":"Drug Metab. Dispos."},{"key":"ref_19","first-page":"5849","article-title":"Anaerobic degradation of flavonoids by Clostridium orbiscindens","volume":"69","author":"Schoefer","year":"2003","journal-title":"Microbiology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.3945\/jn.108.102814","article-title":"The bioavailability of apigenin-7-glucoside is influenced by human intestinal microbiota in rats","volume":"139","author":"Hanske","year":"2009","journal-title":"J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s00203-005-0063-7","article-title":"Differential antibacterial activity of genistein arising from global inhibition of DNA, RNA and protein synthesis in some bacterial strains","volume":"184","author":"Ulanowska","year":"2006","journal-title":"Arch. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1078\/0944-5013-00206","article-title":"Assessment of the antibacterial activity of selected flavonoids and consideration of discrepancies between previous reports","volume":"158","author":"Cushnie","year":"2003","journal-title":"Microbiol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1074\/mcp.M110.002741","article-title":"Proteomics and transcriptomics characterization of bile stress response in probiotic Lactobacillus rhamnosus GG","volume":"10","author":"Koskenniemi","year":"2011","journal-title":"Mol. Cell. Proteom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.anaerobe.2016.10.004","article-title":"The effect of quercetin on genetic expression of the commensal gut microbes Bifidobacterium catenulatum, Enterococcus caccae and Ruminococcus gauvreauii","volume":"42","author":"Firrman","year":"2016","journal-title":"Anaerobe"},{"key":"ref_25","unstructured":"Gilmore, M.S., Clewell, D.B., and Ike, Y. (2014). Enterococcus diversity, origins in nature, and gut colonization. Enterococci: From Commensals to Leading Causes of Drug Resistant Infection, Massachusetts Eye and Ear Infirmary."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1128\/MMBR.00023-12","article-title":"Enterococci in the environment","volume":"76","author":"Byappanahalli","year":"2012","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/4441022a","article-title":"Microbial ecology: Human gut microbes associated with obesity","volume":"444","author":"Ley","year":"2006","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11331","DOI":"10.1021\/jf303165w","article-title":"Gut microbial metabolism of polyphenols from black tea and red wine\/grape juice is source-specific and colon-region dependent","volume":"60","author":"Peters","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1042\/BJ20082222","article-title":"The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: Implications for epithelial protection","volume":"420","author":"Vincent","year":"2009","journal-title":"Biochem. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1136\/gut.52.10.1442","article-title":"Short chain fatty acids stimulate epithelial mucin 2 expression through differential effects on prostaglandin E(1) and E(2) production by intestinal myofibroblasts","volume":"52","author":"Willemsen","year":"2003","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S0140-6736(03)12489-0","article-title":"Gut flora in health and disease","volume":"360","author":"Guarner","year":"2003","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The Microbial Metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Le Bourgeois, P., Bugarel, M., Campo, N., Daveran-Mingot, M.-L., Labont\u00e9, J., Lanfranchi, D., Lautier, T., Pag\u00e8s, C., and Ritzenthaler, P. (2007). The unconventional Xer recombination machinery of Streptococci\/Lactococci. PLoS Genet., 3.","DOI":"10.1371\/journal.pgen.0030117"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1746-1448-2-11","article-title":"The uvrA, uvrB and uvrC genes are required for repair of ultraviolet light induced DNA photoproducts in Halobacterium sp. NRC-1","volume":"2","author":"Crowley","year":"2006","journal-title":"Saline Syst."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.1574-6968.2011.02226.x","article-title":"Functional analysis of Borrelia burgdorferi uvrA in DNA damage protection","volume":"317","author":"Sambir","year":"2011","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7635","DOI":"10.1128\/JB.00903-06","article-title":"The Streptomyces NrdR transcriptional regulator is a Zn ribbon\/ATP cone protein that binds to the promoter regions of class Ia and class II ribonucleotide reductase operons","volume":"188","author":"Grinberg","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1021\/cr040471u","article-title":"Prokaryotic nucleotide excision repair: The UvrABC System","volume":"106","author":"Truglio","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1074\/jbc.M115.674408","article-title":"Novel structural components contribute to the high thermal stability of acyl carrier protein from Enterococcus faecalis","volume":"291","author":"Park","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1128\/JB.01148-13","article-title":"Inefficient translation renders the Enterococcus faecalis fabk enoyl-acyl carrier protein reductase phenotypically cryptic","volume":"196","author":"Bi","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1093\/oxfordjournals.jbchem.a135614","article-title":"Effect of thiolactomycin on the individual enzymes of the fatty acid synthase system in Escherichia coli","volume":"99","author":"Nishida","year":"1986","journal-title":"J. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8376","DOI":"10.1128\/JB.00763-06","article-title":"A homologue of the 3-oxoacyl-(acyl carrier protein) synthase III gene located in the glycosylation island of Pseudomonas syringae pv. tabaci regulates virulence factors via N-acyl homoserine lactone and fatty acid synthesis","volume":"188","author":"Taguchi","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s13213-014-0912-1","article-title":"Gradual pediocin PA-1 resistance in Enterococcus faecalis confers cross-protection to diverse pore-forming cationic antimicrobial peptides displaying changes in cell wall and mannose PTS expression","volume":"65","author":"Kumariya","year":"2015","journal-title":"Ann. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1146\/annurev.biochem.74.082803.133524","article-title":"The structural biology of type II fatty acid biosynthesis","volume":"74","author":"White","year":"2005","journal-title":"Annu. Rev. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mBio.00281-13","article-title":"Daptomycin-resistant Enterococcus faecalis diverts the antibiotic molecule from the division septum and remodels cell membrane phospholipids","volume":"4","author":"Tran","year":"2013","journal-title":"MBio"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1056\/NEJMoa1011138","article-title":"Genetic basis for in vivo daptomycin resistance in enterococci","volume":"365","author":"Arias","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1084\/jem.20020322","article-title":"Synthetic lipoteichoic acid from Staphylococcus aureus is a potent stimulus of cytokine release","volume":"195","author":"Morath","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.1073\/pnas.1005066107","article-title":"Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid","volume":"108","author":"Mohamadzadeh","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"10989","DOI":"10.1021\/ja504125v","article-title":"Multiple complexes of long aliphatic N-acyltransferases lead to synthesis of 2,6-diacylated\/2-acyl-substituted glycopeptide antibiotics, effectively killing vancomycin-resistant Enterococcus","volume":"136","author":"Lyu","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1128\/MMBR.66.4.702-738.2002","article-title":"Biochemistry and comparative genomics of SxxK superfamily acyltransferases offer a clue to the mycobacterial paradox: Presence of penicillin-susceptible target proteins versus lack of efficiency of penicillin as therapeutic agent","volume":"66","author":"Goffin","year":"2002","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1574-6976.2008.00105.x","article-title":"The penicillin-binding proteins: Structure and role in peptidoglycan biosynthesis","volume":"32","author":"Sauvage","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1046\/j.1365-2958.2000.01724.x","article-title":"Role of penicillin-binding protein PBP 2B in assembly and functioning of the division machinery of Bacillus subtilis","volume":"35","author":"Daniel","year":"2000","journal-title":"Mol. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.resmic.2008.06.008","article-title":"Diversity of Firmicutes peptidoglycan hydrolases and specificities of those involved in daughter cell separation","volume":"159","author":"Layec","year":"2008","journal-title":"Res. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4267","DOI":"10.1128\/AAC.00794-13","article-title":"Reducing the level of undecaprenyl pyrophosphate synthase has complex effects on susceptibility to cell wall antibiotics","volume":"57","author":"Lee","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/jmcb\/mjq021","article-title":"Molecular mechanisms of ligand-mediated attenuation of DNA binding by MarR family transcriptional regulators","volume":"2","author":"Perera","year":"2010","journal-title":"J. Mol. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1146\/annurev.micro.091208.073241","article-title":"Management of oxidative stress in Bacillus","volume":"63","author":"Zuber","year":"2009","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_56","first-page":"1","article-title":"Function and control of the Spx-family of proteins within the bacterial stress response","volume":"8","author":"Zuber","year":"2013","journal-title":"Briefs Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev-biochem-060208-092442","article-title":"Molecular chaperone functions in protein folding and proteostasis","volume":"82","author":"Kim","year":"2013","journal-title":"Annu. Rev. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1099\/mic.0.055657-0","article-title":"Proteomic and transcriptomic analysis of the response to bile stress of Lactobacillus casei BL23","volume":"158","year":"2012","journal-title":"Microbiology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0168-6445(03)00055-X","article-title":"Bacterial iron homeostasis","volume":"27","author":"Andrews","year":"2003","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.freeradbiomed.2003.09.022","article-title":"Colonic metabolism of dietary polyphenols: Influence of structure on microbial fermentation products","volume":"36","author":"Rechner","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Wu, G.D., Lewis, J.D., Hoffmann, C., Chen, Y.-Y., Knight, R., Bittinger, K., Hwang, J., Chen, J., Berkowsky, R., and Nessel, L. (2010). Sampling and pyrosequencing methods for characterizing bacterial communities in the human gut using 16S sequence tags. BMC Microbiol., 10.","DOI":"10.1186\/1471-2180-10-206"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"McKenna, P., Hoffmann, C., Minkah, N., Aye, P.P., Lackner, A., Liu, Z., Lozupone, C.A., Hamady, M., Knight, R., and Bushman, F.D. (2008). The macaque gut microbiome in health, lentiviral infection, and chronic enterocolitis. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.0040020"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s40168-017-0267-5","article-title":"Optimizing methods and dodging pitfalls in microbiome research","volume":"5","author":"Kim","year":"2017","journal-title":"Microbiome"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1093\/bioinformatics\/btq461","article-title":"Search and clustering orders of magnitude faster than BLAST","volume":"26","author":"Edgar","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/ismej.2011.139","article-title":"An improved Greengenes taxonomy with explicit ranks for ecological and evolutionary analyses of bacteria and archaea","volume":"6","author":"McDonald","year":"2012","journal-title":"ISME J."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Price, M.N., Dehal, P.S., and Arkin, A.P. (2010). FastTree 2\u2014Approximately maximum-likelihood trees for large alignments. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009490"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nmeth.1226","article-title":"Mapping and quantifying mammalian transcriptomes by RNA-Seq","volume":"5","author":"Mortazavi","year":"2008","journal-title":"Nat. Methods"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/8\/1292\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:45:05Z","timestamp":1760208305000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/8\/1292"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,3]]},"references-count":68,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["molecules22081292"],"URL":"https:\/\/doi.org\/10.3390\/molecules22081292","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,3]]}}}