{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T08:45:22Z","timestamp":1769935522366,"version":"3.49.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04469\/2020"],"award-info":[{"award-number":["UIDB\/04469\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-029628"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029628"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/117365\/2016"],"award-info":[{"award-number":["SFRH\/BD\/117365\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/140182\/2018"],"award-info":[{"award-number":["SFRH\/BD\/140182\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04469\/2020"],"award-info":[{"award-number":["UIDB\/04469\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04469\/2020"],"award-info":[{"award-number":["UIDB\/04469\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-029628"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029628"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-029182"],"award-info":[{"award-number":["POCI-01-0145-FEDER-029182"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Ministry of Education and Science | Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/04469\/2020"],"award-info":[{"award-number":["UIDB\/04469\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["UNLOCK project NRGWI.obrug.2018.005"],"award-info":[{"award-number":["UNLOCK project NRGWI.obrug.2018.005"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Biofilms Microbiomes"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lytic bacteriophages are considered safe for human consumption as biocontrol agents against foodborne pathogens, in particular in ready-to-eat foodstuffs. Phages could, however, evolve to infect different hosts when passing through the gastrointestinal tract (GIT). This underlines the importance of understanding the impact of phages towards colonic microbiota, particularly towards bacterial families usually found in the colon such as the <jats:italic>Enterobacteriaceae<\/jats:italic>. Here we propose in vitro batch fermentation as model for initial safety screening of lytic phages targeting Shiga toxin-producing <jats:italic>Escherichia coli<\/jats:italic> (STEC). As inoculum we used faecal material of three healthy donors. To assess phage safety, we monitored fermentation parameters, including short chain fatty acid production and gas production\/intake by colonic microbiota. We performed shotgun metagenomic analysis to evaluate the outcome of phage interference with colonic microbiota composition and functional potential. During the 24\u2009h incubation, concentrations of phage and its host were also evaluated. We found the phage used in this study, named <jats:italic>E. coli<\/jats:italic> phage vB_EcoS_Ace (Ace), to be safe towards human colonic microbiota, independently of the donors\u2019 faecal content used. This suggests that individuality of donor faecal microbiota did not interfere with phage effect on the fermentations. However, the model revealed that the attenuated STEC strain used as phage host perturbed the faecal microbiota as based on metagenomic analysis, with potential differences in metabolic output. We conclude that the in vitro batch fermentation model used in this study is a reliable safety screening for lytic phages intended to be used as biocontrol agents.<\/jats:p>","DOI":"10.1038\/s41522-022-00334-8","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T04:02:41Z","timestamp":1664164961000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["An in vitro fermentation model to study the impact of bacteriophages targeting Shiga toxin-encoding Escherichia coli on the colonic microbiota"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9348-7553","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Pinto","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7280-9915","authenticated-orcid":false,"given":"Sudarshan A.","family":"Shetty","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7149-0727","authenticated-orcid":false,"given":"Erwin G.","family":"Zoetendal","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9806-8147","authenticated-orcid":false,"given":"Raquel F. S.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[]},{"given":"Ana C.","family":"Pinheiro","sequence":"additional","affiliation":[]},{"given":"Carina","family":"Almeida","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5180-7133","authenticated-orcid":false,"given":"Joana","family":"Azeredo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6138-5026","authenticated-orcid":false,"given":"Hauke","family":"Smidt","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"334_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pmed.1001923","volume":"12","author":"AH Havelaar","year":"2015","unstructured":"Havelaar, A. H. et al. World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010. PLoS Med. 12, 1\u201323 (2015).","journal-title":"PLoS Med."},{"key":"334_CR2","doi-asserted-by":"publisher","first-page":"e236","DOI":"10.1017\/S095026881900116X","volume":"147","author":"SM Pires","year":"2019","unstructured":"Pires, S. M., Majowicz, S., Gill, A. & Devleesschauwer, B. Global and regional source attribution of shiga toxin-producing Escherichia coli infections using analysis of outbreak surveillance data. Epidemiol. Infect. 147, e236 (2019).","journal-title":"Epidemiol. Infect"},{"key":"334_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2016.00825","volume":"7","author":"D Guti\u00e9rrez","year":"2016","unstructured":"Guti\u00e9rrez, D., Rodr\u00edguez-Rubio, L., Mart\u00ednez, B., Rodr\u00edguez, A. & Garc\u00eda, P. Bacteriophages as weapons against bacterial biofilms in the food industry. Front. Microbiol. 7, 1\u201315 (2016).","journal-title":"Front. Microbiol."},{"key":"334_CR4","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.copbio.2020.10.003","volume":"68","author":"M Gambino","year":"2021","unstructured":"Gambino, M. & Br\u00f8ndsted, L. Looking into the future of phage-based control of zoonotic pathogens in food and animal production. Curr. Opin. Biotechnol. 68, 96\u2013103 (2021).","journal-title":"Curr. Opin. Biotechnol."},{"key":"334_CR5","doi-asserted-by":"crossref","unstructured":"Amarillas, L., Chaidez, C., Gonz\u00e1lez-Robles, A., Lugo-Melchor, Y. & Le\u00f3n-F\u00e9lix, J. Characterization of novel bacteriophage phiC119 capable of lysing multidrugresistant Shiga toxin-producing Escherichia coli O157:H7. PeerJ 4, e2423 (2016).","DOI":"10.7717\/peerj.2423"},{"key":"334_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12985-019-1269-7","volume":"17","author":"YD Niu","year":"2020","unstructured":"Niu, Y. D., Liu, H., Johnson, R. P., McAllister, T. A. & Stanford, K. Effect of a bacteriophage T5virus on growth of Shiga toxigenic Escherichia coli and Salmonella strains in individual and mixed cultures. Virol. J. 17, 1\u20137 (2020).","journal-title":"Virol. J."},{"key":"334_CR7","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3390\/antibiotics7040101","volume":"7","author":"C Howard-Varona","year":"2018","unstructured":"Howard-Varona, C. et al. Fighting fire with fire: phage potential for the treatment of E. coli o157 infection. Antibiotics 7, 101 (2018).","journal-title":"Antibiotics"},{"key":"334_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fcimb.2013.00020","volume":"3","author":"D Tomat","year":"2013","unstructured":"Tomat, D., Migliore, L., Aquili, V., Quiberoni, A. & Balagu\u00e9, C. Phage biocontrol of enteropathogenic and shiga toxin-producing Escherichia coli in meat products. Front. Cell. Infect. Microbiol. 3, 1\u201310 (2013).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"334_CR9","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1093\/femsre\/fuaa017","volume":"44","author":"DP Pires","year":"2020","unstructured":"Pires, D. P., Costa, A. R., Pinto, G., Meneses, L. & Azeredo, J. Current challenges and future opportunities of phage therapy. FEMS Microbiol. Rev. 44, 684\u2013700 (2020).","journal-title":"FEMS Microbiol. Rev."},{"key":"334_CR10","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/1471-2180-12-160","volume":"12","author":"D Corogeanu","year":"2012","unstructured":"Corogeanu, D. et al. Therapeutic concentrations of antibiotics inhibit Shiga toxin release from enterohemorrhagic E. coli O104:H4 from the 2011 German outbreak. BMC Microbiol. 12, 160 (2012).","journal-title":"BMC Microbiol"},{"key":"334_CR11","doi-asserted-by":"publisher","first-page":"93","DOI":"10.5937\/tehmesa1402093N","volume":"55","author":"I Nastasijevi\u0107","year":"2015","unstructured":"Nastasijevi\u0107, I., Mitrovi\u0107, R. & Jankovi\u0107, V. STEC in the beef chain: one health approach. Tehnol. mesa 55, 93\u2013116 (2015).","journal-title":"Tehnol. mesa"},{"key":"334_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/femsec\/fiab105","volume":"97","author":"G Pinto","year":"2021","unstructured":"Pinto, G. et al. The interactions of bacteriophage Ace and Shiga toxin-producing Escherichia coli during biocontrol. FEMS Microbiol. Ecol. 97, 1\u201315 (2021).","journal-title":"FEMS Microbiol. Ecol."},{"key":"334_CR13","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1080\/1040841X.2020.1729695","volume":"46","author":"LDR Melo","year":"2020","unstructured":"Melo, L. D. R., Oliveira, H., Pires, D. P., Dabrowska, K. & Azeredo, J. Phage therapy efficacy: a review of the last 10 years of preclinical studies. Crit. Rev. Microbiol. 46, 78\u201399 (2020).","journal-title":"Crit. Rev. Microbiol."},{"key":"334_CR14","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1128\/AEM.06231-11","volume":"78","author":"M Park","year":"2012","unstructured":"Park, M. et al. Characterization and comparative genomic analysis of a novel bacteriophage, SFP10, simultaneously inhibiting both Salmonella enterica and Escherichia coli O157:H7. Appl. Environ. Microbiol. 78, 58\u201369 (2012).","journal-title":"Appl. Environ. Microbiol."},{"key":"334_CR15","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.chom.2017.10.010","volume":"22","author":"L De Sordi","year":"2017","unstructured":"De Sordi, L., Khanna, V. & Debarbieux, L. The gut microbiota facilitates drifts in the genetic diversity and infectivity of bacterial viruses. Cell Host Microbe 22, 801\u2013808.e3 (2017).","journal-title":"Cell Host Microbe"},{"key":"334_CR16","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1038\/s41396-019-0435-7","volume":"13","author":"JNV Martinson","year":"2019","unstructured":"Martinson, J. N. V. et al. Rethinking gut microbiome residency and the Enterobacteriaceae in healthy human adults. ISME J. 13, 2306\u20132318 (2019).","journal-title":"ISME J."},{"key":"334_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2018.01835","volume":"9","author":"ZY Kho","year":"2018","unstructured":"Kho, Z. Y. & Lal, S. K. The human gut microbiome\u2014a potential controller of wellness and disease. Front. Microbiol. 9, 1\u201323 (2018).","journal-title":"Front. Microbiol."},{"key":"334_CR18","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.jconrel.2020.06.016","volume":"326","author":"PJ Voorhees","year":"2020","unstructured":"Voorhees, P. J., Cruz-Teran, C., Edelstein, J. & Lai, S. K. Challenges & opportunities for phage-based in situ microbiome engineering in the gut. J. Control. Release 326, 106\u2013119 (2020).","journal-title":"J. Control. Release"},{"key":"334_CR19","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.3390\/ijms20081925","volume":"20","author":"I Tsitko","year":"2019","unstructured":"Tsitko, I. et al. A small in vitro fermentation model for screening the gut microbiota effects of different fiber preparations. Int. J. Mol. Sci. 20, 1925 (2019).","journal-title":"Int. J. Mol. Sci"},{"key":"334_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0160533","volume":"11","author":"R Takagi","year":"2016","unstructured":"Takagi, R. et al. A single-batch fermentation system to simulate human colonic microbiota for high-throughput evaluation of prebiotics. PLoS ONE 11, 1\u201316 (2016).","journal-title":"PLoS ONE"},{"key":"334_CR21","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.mimet.2016.08.002","volume":"129","author":"MM O\u2019Donnell","year":"2016","unstructured":"O\u2019Donnell, M. M. et al. Preparation of a standardised faecal slurry for ex-vivo microbiota studies which reduces inter-individual donor bias. J. Microbiol. Methods 129, 109\u2013116 (2016).","journal-title":"J. Microbiol. Methods"},{"key":"334_CR22","doi-asserted-by":"publisher","first-page":"79","DOI":"10.3109\/09637486.2013.825700","volume":"65","author":"NA Khalil","year":"2014","unstructured":"Khalil, N. A., Walton, G. E., Gibson, G. R., Tuohy, K. M. & Andrews, S. C. In vitro batch cultures of gut microbiota from healthy and ulcerative colitis (UC) subjects suggest that sulphate-reducing bacteria levels are raised in UC and by a protein-rich diet. Int. J. Food Sci. Nutr. 65, 79\u201388 (2014).","journal-title":"Int. J. Food Sci. Nutr."},{"key":"334_CR23","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1039\/C3FO60702J","volume":"5","author":"M Minekus","year":"2014","unstructured":"Minekus, M. et al. A standardised static in vitro digestion method suitable for food-an international consensus. Food Funct. 5, 1113\u20131124 (2014).","journal-title":"Food Funct."},{"key":"334_CR24","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1007\/s002530051622","volume":"53","author":"M Minekus","year":"1999","unstructured":"Minekus, M. et al. A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products. Appl. Microbiol. Biotechnol. 53, 108\u2013114 (1999).","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"334_CR25","doi-asserted-by":"publisher","first-page":"1800232","DOI":"10.1002\/mnfr.201800232","volume":"62","author":"F Gu","year":"2018","unstructured":"Gu, F. et al. In vitro fermentation behavior of isomalto\/malto-polysaccharides using human fecal inoculum indicates prebiotic potential. Mol. Nutr. Food Res. 62, 1800232 (2018).","journal-title":"Mol. Nutr. Food Res"},{"key":"334_CR26","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.bcdf.2013.09.008","volume":"2","author":"F Hugenholtz","year":"2013","unstructured":"Hugenholtz, F., Mullaney, J. A., Kleerebezem, M., Smidt, H. & Rosendale, D. I. Modulation of the microbial fermentation in the gut by fermentable carbohydrates. Bioact. Carbohydr. Diet. Fibre 2, 133\u2013142 (2013).","journal-title":"Bioact. Carbohydr. Diet. Fibre"},{"key":"334_CR27","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3920\/BM2014.0151","volume":"7","author":"HR Cardarelli","year":"2016","unstructured":"Cardarelli, H. R. et al. In vitro fermentation of prebiotic carbohydrates by intestinal microbiota in the presence of Lactobacillus amylovorus DSM 16998. Benef. Microbes 7, 119\u2013133 (2016).","journal-title":"Benef. Microbes"},{"key":"334_CR28","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1055\/s-2001-18537","volume":"39","author":"A Bender","year":"2001","unstructured":"Bender, A. et al. Colonic fermentation as affected by antibiotics and acidic pH: application of an in vitro model. Z. Gastroenterol. 39, 911\u2013918 (2001).","journal-title":"Z. Gastroenterol."},{"key":"334_CR29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep39235","volume":"6","author":"FL Nobrega","year":"2016","unstructured":"Nobrega, F. L. et al. Genetically manipulated phages with improved pH resistance for oral administration in veterinary medicine. Sci. Rep. 6, 1\u201312 (2016).","journal-title":"Sci. Rep."},{"key":"334_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2017.00467","volume":"8","author":"R Mi\u0229dzybrodzki","year":"2017","unstructured":"Mi\u0229dzybrodzki, R. et al. Means to facilitate the overcoming of gastric juice barrier by a therapeutic staphylococcal bacteriophage A5\/80. Front. Microbiol. 8, 1\u201311 (2017).","journal-title":"Front. Microbiol."},{"key":"334_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-43115-8","volume":"9","author":"LDR Melo","year":"2019","unstructured":"Melo, L. D. R., Ferreira, R., Costa, A. R., Oliveira, H. & Azeredo, J. Efficacy and safety assessment of two enterococci phages in an in vitro biofilm wound model. Sci. Rep. 9, 1\u201312 (2019).","journal-title":"Sci. Rep."},{"key":"334_CR32","doi-asserted-by":"crossref","unstructured":"Liao, Y. Te et al. Characterization of a lytic bacteriophage as an antimicrobial agent for biocontrol of shiga toxin-producing escherichia coli o145 strains. Antibiotics 8, 74 (2019).","DOI":"10.3390\/antibiotics8020074"},{"key":"334_CR33","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1080\/07315724.2009.10719798","volume":"28","author":"A Maathuis","year":"2009","unstructured":"Maathuis, A., Venema, K., Hoffman, A., Evans, A. & Sanders, L. The effect of the undigested fraction of maize products on the activity and composition of the microbiota determined in a dynamic in vitro model of the human proximal large intestine. J. Am. Coll. Nutr. 28, 657\u2013666 (2009).","journal-title":"J. Am. Coll. Nutr."},{"key":"334_CR34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmicb.2019.01676","volume":"10","author":"S Iacob","year":"2019","unstructured":"Iacob, S., Iacob, D. G. & Luminos, L. M. Intestinal microbiota as a host defense mechanism to infectious threats. Front. Microbiol. 10, 1\u20139 (2019).","journal-title":"Front. Microbiol."},{"key":"334_CR35","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1038\/s41592-018-0176-y","volume":"15","author":"EA Franzosa","year":"2018","unstructured":"Franzosa, E. A. et al. Species-level functional profiling of metagenomes and metatranscriptomes. Nat. Methods 15, 962\u2013968 (2018).","journal-title":"Nat. Methods"},{"key":"334_CR36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mimet.2014.08.022","volume":"107","author":"M Aguirre","year":"2014","unstructured":"Aguirre, M., Ramiro-Garcia, J., Koenen, M. E. & Venema, K. To pool or not to pool? Impact of the use of individual and pooled fecal samples for in vitro fermentation studies. J. Microbiol. Methods 107, 1\u20137 (2014).","journal-title":"J. Microbiol. Methods"},{"key":"334_CR37","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.mimet.2013.08.008","volume":"95","author":"JAK McDonald","year":"2013","unstructured":"McDonald, J. A. K. et al. Evaluation of microbial community reproducibility, stability and composition in a human distal gut chemostat model. J. Microbiol. Methods 95, 167\u2013174 (2013).","journal-title":"J. Microbiol. Methods"},{"key":"334_CR38","first-page":"391","volume":"9","author":"T Cieplak","year":"2018","unstructured":"Cieplak, T., Soffer, N., Sulakvelidze, A. & Nielsen, D. S. A bacteriophage cocktail targeting Escherichia coli reduces E. coli in simulated gut conditions, while preserving a non-targeted representative commensal normal microbiota. Gut Microbes 9, 391\u2013399 (2018).","journal-title":"Gut Microbes"},{"key":"334_CR39","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/j.chom.2019.05.001","volume":"25","author":"BB Hsu","year":"2019","unstructured":"Hsu, B. B. et al. Dynamic modulation of the gut microbiota and metabolome by bacteriophages in a mouse model. Cell Host Microbe 25, 803\u2013814.e5 (2019).","journal-title":"Cell Host Microbe"},{"key":"334_CR40","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.resmic.2011.06.010","volume":"162","author":"D Pires","year":"2011","unstructured":"Pires, D., Sillankorva, S., Faustino, A. & Azeredo, J. Use of newly isolated phages for control of Pseudomonas aeruginosa PAO1 and ATCC 10145 biofilms. Res. Microbiol. 162, 798\u2013806 (2011).","journal-title":"Res. Microbiol."},{"key":"334_CR41","doi-asserted-by":"publisher","first-page":"108791","DOI":"10.1016\/j.foodres.2019.108791","volume":"128","author":"D Alves","year":"2020","unstructured":"Alves, D., Cerqueira, M. A., Pastrana, L. M. & Sillankorva, S. Entrapment of a phage cocktail and cinnamaldehyde on sodium alginate emulsion-based films to fight food contamination by Escherichia coli and Salmonella Enteritidis. Food Res. Int. 128, 108791 (2020).","journal-title":"Food Res. Int."},{"key":"334_CR42","doi-asserted-by":"publisher","first-page":"2750","DOI":"10.1128\/aem.54.11.2750-2755.1988","volume":"54","author":"GR Gibson","year":"1988","unstructured":"Gibson, G. R., Cummings, J. H. & Macfarlane, G. T. Use of a three-stage continuous culture system to study the effect of mucin on dissimilatory sulfate reduction and methanogenesis by mixed populations of human gut bacteria. Appl. Environ. Microbiol. 54, 2750\u20132755 (1988).","journal-title":"Appl. Environ. Microbiol."},{"key":"334_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0113864","volume":"9","author":"M Aguirre","year":"2014","unstructured":"Aguirre, M., Jonkers, D. M. A. E., Troost, F. J., Roeselers, G. & Venema, K. In vitro characterization of the impact of different substrates on metabolite production, energy extraction and composition of gut microbiota from lean and obese subjects. PLoS ONE 9, 1\u201323 (2014).","journal-title":"PLoS ONE"},{"key":"334_CR44","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.mimet.2015.07.019","volume":"117","author":"M Aguirre","year":"2015","unstructured":"Aguirre, M. et al. Evaluation of an optimal preparation of human standardized fecal inocula for in vitro fermentation studies. J. Microbiol. Methods 117, 78\u201384 (2015).","journal-title":"J. Microbiol. Methods"},{"key":"334_CR45","doi-asserted-by":"publisher","first-page":"100235","DOI":"10.1016\/j.bcdf.2020.100235","volume":"24","author":"MJ Logtenberg","year":"2020","unstructured":"Logtenberg, M. J. et al. Pooled faecal inoculum can predict infant fiber fermentability despite high inter-individual variability of microbiota composition. Bioact. Carbohydr. Diet. Fibre 24, 100235 (2020).","journal-title":"Bioact. Carbohydr. Diet. Fibre"},{"key":"334_CR46","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3389\/fmicb.2020.00058","volume":"11","author":"AL Arantes","year":"2020","unstructured":"Arantes, A. L. et al. Enrichment of anaerobic syngas-converting communities and isolation of a novel carboxydotrophic Acetobacterium wieringae strain JM. Front. Microbiol. 11, 58 (2020).","journal-title":"Front. Microbiol"},{"key":"334_CR47","unstructured":"Bushnell, Brian. BBMap: a fast, accurate, splice-aware aligner. No. LBNL-7065E. Lawrence Berkeley National Lab.(LBNL), Berkeley, CA (United States), 2014."},{"key":"334_CR48","unstructured":"Babraham Bioinformatics\u2014FastQC a quality control tool for high throughput sequence data. https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"334_CR49","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s12038-019-9930-2","volume":"44","author":"SA Shetty","year":"2019","unstructured":"Shetty, S. A. & Lahti, L. Microbiome data science. J. Biosci. 44, 115 (2019).","journal-title":"J. Biosci"},{"key":"334_CR50","first-page":"1","volume":"1","author":"J Oksanen","year":"2008","unstructured":"Oksanen, J. Vegan: an introduction to ordination. Management 1, 1\u201310 (2008).","journal-title":"Management"},{"key":"334_CR51","doi-asserted-by":"publisher","first-page":"4863","DOI":"10.1111\/1462-2920.15269","volume":"22","author":"SA Shetty","year":"2020","unstructured":"Shetty, S. A., Boeren, S., Bui, T. P. N., Smidt, H. & de Vos, W. M. Unravelling lactate-acetate and sugar conversion into butyrate by intestinal Anaerobutyricum and Anaerostipes species by comparative proteogenomics. Environ. Microbiol. 22, 4863\u20134875 (2020).","journal-title":"Environ. Microbiol."},{"key":"334_CR52","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","volume":"31","author":"S Anders","year":"2015","unstructured":"Anders, S., Pyl, P. T. & Huber, W. HTSeq-A Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166\u2013169 (2015).","journal-title":"Bioinformatics"}],"container-title":["npj Biofilms and Microbiomes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41522-022-00334-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41522-022-00334-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41522-022-00334-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T04:03:59Z","timestamp":1664165039000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41522-022-00334-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,26]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["334"],"URL":"https:\/\/doi.org\/10.1038\/s41522-022-00334-8","relation":{},"ISSN":["2055-5008"],"issn-type":[{"value":"2055-5008","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,26]]},"assertion":[{"value":"7 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"74"}}