{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:27:29Z","timestamp":1790807249396,"version":"4.1.0"},"reference-count":100,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T00:00:00Z","timestamp":1697328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Generalitat Valenciana-Fondo Social Europeo","award":["ACIF\/2020\/376"],"award-info":[{"award-number":["ACIF\/2020\/376"]}]},{"name":"Generalitat Valenciana-Fondo Social Europeo","award":["INDI 21\/35"],"award-info":[{"award-number":["INDI 21\/35"]}]},{"name":"Generalitat Valenciana-Fondo Social Europeo","award":["ISP 60386"],"award-info":[{"award-number":["ISP 60386"]}]},{"name":"Centre for Poultry Quality and Animal Feed of the Valencian Community (CECAV)","award":["ACIF\/2020\/376"],"award-info":[{"award-number":["ACIF\/2020\/376"]}]},{"name":"Centre for Poultry Quality and Animal Feed of the Valencian Community (CECAV)","award":["INDI 21\/35"],"award-info":[{"award-number":["INDI 21\/35"]}]},{"name":"Centre for Poultry Quality and Animal Feed of the Valencian Community (CECAV)","award":["ISP 60386"],"award-info":[{"award-number":["ISP 60386"]}]},{"name":"MSD","award":["ACIF\/2020\/376"],"award-info":[{"award-number":["ACIF\/2020\/376"]}]},{"name":"MSD","award":["INDI 21\/35"],"award-info":[{"award-number":["INDI 21\/35"]}]},{"name":"MSD","award":["ISP 60386"],"award-info":[{"award-number":["ISP 60386"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bacteriophage therapy is considered one of the most promising tools to control zoonotic bacteria, such as Salmonella, in broiler production. Phages exhibit high specificity for their targeted bacterial hosts, causing minimal disruption to the niche microbiota. However, data on the gut environment\u2019s response to phage therapy in poultry are limited. This study investigated the influence of Salmonella phage on host physiology through caecal microbiota and metabolome modulation using high-throughput 16S rRNA gene sequencing and an untargeted metabolomics approach. We employed 24 caecum content samples and 24 blood serum samples from 4-, 5- and 6-week-old broilers from a previous study where Salmonella phages were administered via feed in Salmonella-infected broilers, which were individually weighed weekly. Phage therapy did not affect the alpha or beta diversity of the microbiota. Specifically, we observed changes in the relative abundance of 14 out of the 110 genera using the PLS-DA and Bayes approaches. On the other hand, we noted changes in the caecal metabolites (63 up-accumulated and 37 down-accumulated out of the 1113 caecal metabolites). Nevertheless, the minimal changes in blood serum suggest a non-significant physiological response. The application of Salmonella phages under production conditions modulates the caecal microbiome and metabolome profiles in broilers without impacting the host physiology in terms of growth performance.<\/jats:p>","DOI":"10.3390\/ijms242015201","type":"journal-article","created":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T10:47:32Z","timestamp":1697366852000},"page":"15201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Modulation of Caecal Microbiota and Metabolome Profile in Salmonella-Infected Broilers by Phage Therapy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4759-258X","authenticated-orcid":false,"given":"Laura","family":"Lorenzo-Rebenaque","sequence":"first","affiliation":[{"name":"Department of Animal Production and Health, Veterinary Public Health and Food Science and Technology, Biomedical Research Institute, Faculty of Veterinary Medicine, Cardenal Herrera-CEU University, CEU Universities, Calle Santiago Ram\u00f3n y Cajal 20, Alfara del Patriarca, 45115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Casto-Rebollo","sequence":"additional","affiliation":[{"name":"Institute for Animal Science and Technology, Universitat Polit\u00e8cnica de Val\u00e8ncia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-0233","authenticated-orcid":false,"given":"Gianfranco","family":"Diretto","sequence":"additional","affiliation":[{"name":"Italian Agency for New Technologies, Energy and Sustainable Development (ENEA), Biotechnology Laboratory, Centro Ricerche Casaccia, Via Anguillarese, 301, Santa Maria di Galeria, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8161-3797","authenticated-orcid":false,"given":"Sarah","family":"Frusciante","sequence":"additional","affiliation":[{"name":"Italian Agency for New Technologies, Energy and Sustainable Development (ENEA), Biotechnology Laboratory, Centro Ricerche Casaccia, Via Anguillarese, 301, Santa Maria di Galeria, 00123 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8007-5739","authenticated-orcid":false,"given":"Juan Carlos","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Microbiology Department, Dr. Balmis University General Hospital, Microbiology Division, Miguel Hern\u00e1ndez University, ISABIAL, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-0949","authenticated-orcid":false,"given":"Mar\u00eda-Paz","family":"Ventero","sequence":"additional","affiliation":[{"name":"Microbiology Department, Dr. Balmis University General Hospital, ISABIAL, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0562-6104","authenticated-orcid":false,"given":"Carmen","family":"Molina-Pardines","sequence":"additional","affiliation":[{"name":"Microbiology Department, Dr. Balmis University General Hospital, ISABIAL, 03010 Alicante, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4220-6029","authenticated-orcid":false,"given":"Santiago","family":"Vega","sequence":"additional","affiliation":[{"name":"Department of Animal Production and Health, Veterinary Public Health and Food Science and Technology, Biomedical Research Institute, Faculty of Veterinary Medicine, Cardenal Herrera-CEU University, CEU Universities, Calle Santiago Ram\u00f3n y Cajal 20, Alfara del Patriarca, 45115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6152-3778","authenticated-orcid":false,"given":"Clara","family":"Marin","sequence":"additional","affiliation":[{"name":"Department of Animal Production and Health, Veterinary Public Health and Food Science and Technology, Biomedical Research Institute, Faculty of Veterinary Medicine, Cardenal Herrera-CEU University, CEU Universities, Calle Santiago Ram\u00f3n y Cajal 20, Alfara del Patriarca, 45115 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5226-4118","authenticated-orcid":false,"given":"Francisco","family":"Marco-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Institute for Animal Science and Technology, Universitat Polit\u00e8cnica de Val\u00e8ncia, 46022 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tzani, M., Mandilara, G., Dias, J.G., Sideroglou, T., Chrysostomou, A., and Mellou, K. (2021). Impact of Salmonella Control Programmes in Poultry on Human Salmonellosis Burden in Greece. Antibiotics, 10.","DOI":"10.3390\/antibiotics10020121"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101716","DOI":"10.1016\/j.psj.2022.101716","article-title":"The Control of Poultry Salmonellosis Using Organic Agents: An Updated Overview","volume":"101","author":"Salem","year":"2022","journal-title":"Poult. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"EFSA (2021). ECDC The European Union One Health 2020 Zoonoses Report. EFSA J., 19, e06406.","DOI":"10.2903\/j.efsa.2021.6971"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101968","DOI":"10.1016\/j.psj.2022.101968","article-title":"Research Note: Persistent Salmonella Problems in Slaughterhouses Related to Clones Linked to Poultry Companies","volume":"101","author":"Marin","year":"2022","journal-title":"Poult. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101696","DOI":"10.1016\/j.psj.2022.101696","article-title":"Alternatives to Antibiotics for Organic Poultry Production: Types, Modes of Action and Impacts on Bird\u2019s Health and Production","volume":"101","author":"Salem","year":"2022","journal-title":"Poult. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"916473","DOI":"10.3389\/fvets.2022.916473","article-title":"Potential Feed Additives as Antibiotic Alternatives in Broiler Production","volume":"9","author":"Ayalew","year":"2022","journal-title":"Front. Vet. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s12985-017-0849-7","article-title":"Bacteriophage Therapy to Combat Bacterial Infections in Poultry","volume":"14","author":"Wernicki","year":"2017","journal-title":"Virol. J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"\u017bbikowska, K., Michalczuk, M., and Dolka, B. (2020). The Use of Bacteriophages in the Poultry Industry. Animals, 10.","DOI":"10.3390\/ani10050872"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ruvalcaba-G\u00f3mez, J.M., Villagr\u00e1n, Z., Valdez-Alarc\u00f3n, J.J., Mart\u00ednez-N\u00fa\u00f1ez, M., Gomez-God\u00ednez, L.J., Ruesga-Guti\u00e9rrez, E., Anaya-Esparza, L.M., Arteaga-Garibay, R.I., and Villarruel-L\u00f3pez, A. (2022). Non-Antibiotics Strategies to Control Salmonella Infection in Poultry. Animals, 12.","DOI":"10.3390\/ani12010102"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhao, H., Li, Y., Lv, P., Huang, J., Tai, R., Jin, X., Wang, J., and Wang, X. (2022). Salmonella Phages Affect the Intestinal Barrier in Chicks by Altering the Composition of Early Intestinal Flora: Association with Time of Phage Use. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.947640"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/s41598-021-04679-6","article-title":"The Gut Microbiota of Chickens in a Commercial Farm Treated with a Salmonella Phage Cocktail","volume":"12","author":"Clavijo","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_12","first-page":"391","article-title":"Gut Microbes A Bacteriophage Cocktail Targeting Escherichia Coli Reduces E. Coli in Simulated Gut Conditions, While Preserving a Non-Targeted Representative Commensal Normal Microbiota","volume":"9","author":"Cieplak","year":"2018","journal-title":"Gut Microbes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/07315724.2018.1483783","article-title":"Bacteriophage for Gastrointestinal Health (PHAGE) Study: Evaluating the Safety and Tolerability of Supplemental Bacteriophage Consumption","volume":"38","author":"Gindin","year":"2019","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1093\/ps\/86.9.1904","article-title":"Ability of Bacteriophages Isolated from Different Sources to Reduce Salmonella Enterica Serovar Enteritidis in Vitro and in Vivo","volume":"86","author":"Higgins","year":"2007","journal-title":"Poult. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1637\/8406-071008-Reg.1","article-title":"El Tratamiento Por Aerosol Con Bacteri\u00f3fagos y Exclusi\u00f3n Competitiva Reduce La Infecci\u00f3n Con Salmonella Enteritidis En Pollos","volume":"53","author":"Borie","year":"2009","journal-title":"Avian Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1016\/j.rvsc.2012.06.004","article-title":"Use of Bacteriophage for Biological Control of Salmonella Enteritidis Infection in Chicken","volume":"93","author":"Lim","year":"2012","journal-title":"Res. Vet. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"956833","DOI":"10.3389\/fimmu.2022.956833","article-title":"Highly Different Effects of Phage Therapy and Antibiotic Therapy on Immunological Responses of Chickens Infected with Salmonella Enterica Serovar Typhimurium","volume":"13","author":"Grabowski","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lorenzo-Rebenaque, L., Malik, D.J., Catal\u00e1-Gregori, P., Torres, J., Marin, C., and Sevilla-Navarro, S. (2022). Microencapsulated Bacteriophages Incorporated in Feed for Salmonella Control in Broilers. Vet. Microbiol., 274.","DOI":"10.1016\/j.vetmic.2022.109579"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Peh, E., Szott, V., Reichelt, B., Friese, A., R\u00f6sler, U., Pl\u00f6tz, M., and Kittler, S. (2023). Bacteriophage Cocktail Application for Campylobacter Mitigation\u2014from in Vitro to in Vivo. BMC Microbiol., 23.","DOI":"10.1186\/s12866-023-02963-1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12198","DOI":"10.1038\/s41598-023-38791-6","article-title":"Effects of Bacteriophage on Salmonella Enteritidis Infection in Broilers","volume":"13","author":"Sarrami","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2217947","DOI":"10.1080\/22221751.2023.2217947","article-title":"A Bacteriophage Cocktail Delivered in Feed Significantly Reduced Salmonella Colonization in Challenged Broiler Chickens","volume":"12","author":"Thanki","year":"2023","journal-title":"Emerg. Microbes Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nature18849","article-title":"Interactions between the Microbiota and Pathogenic Bacteria in the Gut","volume":"535","author":"Sperandio","year":"2016","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kosznik-Kwa\u015bnicka, K., Podlacha, M., Grabowski, \u0141., Stasi\u0142oj\u0107, M., Nowak-Zaleska, A., Ciemi\u0144ska, K., Cyske, Z., Dydecka, A., Gaffke, L., and Mantej, J. (2022). Biological Aspects of Phage Therapy versus Antibiotics against Salmonella Enterica Serovar Typhimurium Infection of Chickens. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.941867"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.jfma.2018.09.007","article-title":"Metabolome Analysis for Investigating Host-Gut Microbiota Interactions","volume":"118","author":"Chen","year":"2019","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"454","DOI":"10.3389\/fgene.2019.00454","article-title":"Multi-Omic Analysis of the Microbiome and Metabolome in Healthy Subjects Reveals Microbiome-Dependent Relationships between Diet and Metabolites","volume":"10","author":"Tang","year":"2019","journal-title":"Front. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trac.2011.08.009","article-title":"Metabolite Identification and Quantitation in LC-MS\/MS-Based Metabolomics","volume":"32","author":"Xiao","year":"2012","journal-title":"TrAC\u2014Trends Anal. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ye, X., Zhou, L., Zhang, Y., Xue, S., Gan, Q.F., and Fang, S. (2021). Effect of Host Breeds on Gut Microbiome and Serum Metabolome in Meat Rabbits. BMC Vet. Res., 17.","DOI":"10.1186\/s12917-020-02732-6"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Grzymajlo, K. (2022). The Game for Three: Salmonella\u2013Host\u2013Microbiota Interaction Models. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.854112"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/19490976.2016.1241933","article-title":"Microbiome: Should We Diversify from Diversity?","volume":"7","author":"Johnson","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.4014\/jmb.1304.04067","article-title":"Therapeutic Effects of Bacteriophages against Salmonella Gallinarum Infection in Chickens","volume":"23","author":"Hong","year":"2013","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ahmadi, M., Amir Karimi Torshizi, M., Rahimi, S., and Dennehy, J.J. (2016). Prophylactic Bacteriophage Administration More Effective than Post-Infection Administration in Reducing Salmonella Enterica Serovar Enteritidis Shedding in Quail. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01253"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.3382\/ps\/pex109","article-title":"Effect of Dietary Bacteriophage Supplementation on Internal Organs, Fecal Excretion, and Ileal Immune Response in Laying Hens Challenged by Salmonella Enteritidis","volume":"96","author":"Adhikari","year":"2017","journal-title":"Poult. Sci."},{"key":"ref_33","first-page":"1539056","article-title":"Assessing the Impact of Bacteriophages in the Treatment of Salmonella in Broiler Chickens","volume":"8","author":"Nabil","year":"2018","journal-title":"Infect. Ecol. Epidemiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Vaz, C.S.L., Voss-Rech, D., Alves, L., Coldebella, A., Brentano, L., and Trevisol, I.M. (2020). Effect of Time of Therapy with Wild-Type Lytic Bacteriophages on the Reduction of Salmonella Enteritidis in Broiler Chickens. Vet. Microbiol., 240.","DOI":"10.1016\/j.vetmic.2019.108527"},{"key":"ref_35","first-page":"345","article-title":"Evaluation of the Efficiency of Using Salmonella Kentucky and Escherichia Coli O119 Bacteriophages in the Treatment and Prevention of Salmonellosis and Colibacillosis in Broiler Chickens","volume":"71","author":"Sorour","year":"2020","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41385-019-0250-5","article-title":"New Insights into Intestinal Phages","volume":"13","author":"Sausset","year":"2020","journal-title":"Mucosal Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1111\/1462-2920.13284","article-title":"Bacteriophages to Reduce Gut Carriage of Antibiotic Resistant Uropathogens with Low Impact on Microbiota Composition","volume":"18","author":"Galtier","year":"2016","journal-title":"Environ. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7043","DOI":"10.1038\/s41598-017-07278-6","article-title":"Bacteriophages as Potential New Mammalian Pathogens","volume":"7","author":"Tetz","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dissanayake, U., Ukhanova, M., Moye, Z.D., Sulakvelidze, A., and Mai, V. (2019). Bacteriophages Reduce Pathogenic Escherichia Coli Counts in Mice Without Distorting Gut Microbiota. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01984"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.chom.2019.05.001","article-title":"Dynamic Modulation of the Gut Microbiota and Metabolome by Bacteriophages in a Mouse Model","volume":"25","author":"Hsu","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1060713","DOI":"10.3389\/fgene.2022.1060713","article-title":"Examining the Effects of Salmonella Phage on the Caecal Microbiota and Metabolome Features in Salmonella-Free Broilers","volume":"13","author":"Diretto","year":"2022","journal-title":"Front. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Liu, Y., Lin, Q., Huang, X., Jiang, G., Li, C., Zhang, X., Liu, S., He, L., Liu, Y., and Dai, Q. (2021). Effects of Dietary Ferulic Acid on the Intestinal Microbiota and the Associated Changes on the Growth Performance, Serum Cytokine Profile, and Intestinal Morphology in Ducks. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.698213"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.virol.2012.09.002","article-title":"Oral T4-like Phage Cocktail Application to Healthy Adult Volunteers from Bangladesh","volume":"434","author":"Sarker","year":"2012","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/1462-2920.13574","article-title":"Oral Application of Escherichia Coli Bacteriophage: Safety Tests in Healthy and Diarrheal Children from Bangladesh","volume":"19","author":"Sarker","year":"2017","journal-title":"Environ. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.virol.2013.05.022","article-title":"Safety Analysis of a Russian Phage Cocktail: From Metagenomic Analysis to Oral Application in Healthy Human Subjects","volume":"443","author":"McCallin","year":"2013","journal-title":"Virology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ebiom.2015.12.023","article-title":"Oral Phage Therapy of Acute Bacterial Diarrhea with Two Coliphage Preparations: A Randomized Trial in Children from Bangladesh","volume":"4","author":"Sarker","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Rubinelli, P.M., Kim, S.A., Park, S.H., Roto, S.M., Nealon, N.J., Ryan, E.P., and Ricke, S.C. (2017). Differential Effects of Rice Bran Cultivars to Limit Salmonella Typhimurium in Chicken Cecal in Vitro Incubations and Impact on the Cecal Microbiome and Metabolome. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185002"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101588","DOI":"10.1016\/j.psj.2021.101588","article-title":"Informal Nutrition Symposium: Leveraging the Microbiome (and the Metabolome) for Poultry Production","volume":"101","author":"Lee","year":"2022","journal-title":"Poult. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Aljahdali, N.H., Sanad, Y.M., Han, J., and Foley, S.L. (2020). Current Knowledge and Perspectives of Potential Impacts of Salmonella Enterica on the Profile of the Gut Microbiota. BMC Microbiol., 20.","DOI":"10.1186\/s12866-020-02008-x"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Khan, S., and Chousalkar, K.K. (2020). Salmonella Typhimurium Infection Disrupts but Continuous Feeding of Bacillus Based Probiotic Restores Gut Microbiota in Infected Hens. J. Anim. Sci. Biotechnol., 11.","DOI":"10.1186\/s40104-020-0433-7"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jiang, F., Gao, H., Qin, W., Song, P., Wang, H., Zhang, J., Liu, D., Wang, D., and Zhang, T. (2021). Marked Seasonal Variation in Structure and Function of Gut Microbiota in Forest and Alpine Musk Deer. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.699797"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s12967-022-03280-3","article-title":"Alterations in the Gut Microbiome and Metabolome Profiles of Septic Rats Treated with Aminophylline","volume":"20","author":"Li","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrgastro.2016.168","article-title":"Liver-Guardian, Modifier and Target of Sepsis","volume":"14","author":"Strnad","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Memon, F.U., Yang, Y., Zhang, G., Leghari, I.H., Lv, F., Wang, Y., Laghari, F., Khushk, F.A., and Si, H. (2022). Chicken Gut Microbiota Responses to Dietary Bacillus Subtilis Probiotic in the Presence and Absence of Eimeria Infection. Microorganisms, 10.","DOI":"10.3390\/microorganisms10081548"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e10941","DOI":"10.7717\/peerj.10941","article-title":"Extensive Microbial Diversity within the Chicken Gut Microbiome Revealed by Metagenomics and Culture","volume":"9","author":"Gilroy","year":"2021","journal-title":"PeerJ"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/19476337.2018.1561520","article-title":"Antimicrobial Compounds Produced by Weissella Confusa Cys2-2 Strain Inhibit Gram-Negative Bacteria Growth","volume":"17","author":"Tenea","year":"2019","journal-title":"CYTA J. Food"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"104414","DOI":"10.1016\/j.yrtph.2019.104414","article-title":"Safety Assessment of Weissella Confusa\u2014A Direct-Fed Microbial Candidate","volume":"107","author":"Cupi","year":"2019","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1128\/JB.01328-10","article-title":"Draft Genome Sequence of Turicibacter Sanguinis PC909, Isolated from Human Feces","volume":"193","author":"Klaassens","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"712226","DOI":"10.3389\/fvets.2021.712226","article-title":"The Spatial and Temporal Characterization of Gut Microbiota in Broilers","volume":"8","author":"Zhou","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Baniel, A., Amato, K.R., Beehner, J.C., Bergman, T.J., Mercer, A., Perlman, R.F., Petrullo, L., Reitsema, L., Sams, S., and Lu, A. (2021). Seasonal Shifts in the Gut Microbiome Indicate Plastic Responses to Diet in Wild Geladas. Microbiome, 9.","DOI":"10.1186\/s40168-020-00977-9"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"100935","DOI":"10.1016\/j.psj.2020.12.032","article-title":"Dietary Supplementation with Bacillus Subtilis Promotes Growth Performance of Broilers by Altering the Dominant Microbial Community","volume":"100","author":"Zhang","year":"2021","journal-title":"Poult. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9364","DOI":"10.1038\/s41598-020-66369-z","article-title":"High Oscillospira Abundance Indicates Constipation and Low BMI in the Guangdong Gut Microbiome Project","volume":"10","author":"Chen","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Reyer, H., Sj\u00f6berg, P.J.R., Oster, M., Wubuli, A., Murani, E., Ponsuksili, S., Wolf, P., and Wimmers, K. (2021). Mineral Phosphorus Supply in Piglets Impacts the Microbial Composition and Phytate Utilization in the Large Intestine. Microorganisms, 9.","DOI":"10.3390\/microorganisms9061197"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3389\/fvets.2015.00061","article-title":"Salmonella Enterica Serovars Enteritidis Infection Alters the Indigenous Microbiota Diversity in Young Layer Chicks","volume":"2","author":"Mon","year":"2015","journal-title":"Front. Vet. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Li, Y., Fu, X., Ma, X., Geng, S., Jiang, X., Huang, Q., Hu, C., and Han, X. (2018). Intestinal Microbiome-Metabolome Responses to Essential Oils in Piglets. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01988"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12711-022-00699-6","article-title":"Differences in Caecal Microbiota Composition and Salmonella Carriage between Experimentally Infected Inbred Lines of Chickens","volume":"54","author":"Cazals","year":"2022","journal-title":"Genet. Sel. Evol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Wang, L., Lilburn, M., and Yu, Z. (2016). Intestinal Microbiota of Broiler Chickens as Affected by Litter Management Regimens. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00593"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5809","DOI":"10.3382\/ps\/pez380","article-title":"Changes in Cecum Microbial Community in Response to Total Sulfur Amino Acid (TSAA: DL-Methionine) in Antibiotic-Free and Supplemented Poultry Birds","volume":"98","author":"Kumar","year":"2019","journal-title":"Poult. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"101612","DOI":"10.1016\/j.psj.2021.101612","article-title":"Centennial Review: Factors Affecting the Chicken Gastrointestinal Microbial Composition and Their Association with Gut Health and Productive Performance","volume":"101","author":"Bindari","year":"2022","journal-title":"Poult. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.3382\/ps\/pev182","article-title":"Effect of Lactulose Supplementation on Growth Performance, Intestinal Histomorphology, Cecal Microbial Population, and Short-Chain Fatty Acid Composition of Broiler Chickens","volume":"94","author":"Calik","year":"2015","journal-title":"Poult. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.csbj.2018.03.002","article-title":"Current Perspectives of the Chicken Gastrointestinal Tract and Its Microbiome","volume":"16","author":"Seifert","year":"2018","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.3382\/ps\/pex359","article-title":"The Gastrointestinal Microbiome and Its Association with the Control of Pathogens in Broiler Chicken Production: A Review","volume":"97","author":"Clavijo","year":"2018","journal-title":"Poult. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Yang, D., Zhao, D., Shah, S.Z.A., Wu, W., Lai, M., Zhang, X., Li, J., Guan, Z., Zhao, H., and Li, W. (2020). Implications of Gut Microbiota Dysbiosis and Metabolic Changes in Prion Disease. Neurobiol. Dis., 135.","DOI":"10.1016\/j.nbd.2019.104704"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Carroll-Portillo, A., and Lin, H.C. (2019). Bacteriophage and the Innate Immune System: Access and Signaling. Microorganisms, 7.","DOI":"10.3390\/microorganisms7120625"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3730519","DOI":"10.1155\/2019\/3730519","article-title":"Bacteriophages: Uncharacterized and Dynamic Regulators of the Immune System","volume":"2019","author":"Sinha","year":"2019","journal-title":"Mediators Inflamm."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"van Belleghem, J.D., D\u0105browska, K., Vaneechoutte, M., Barr, J.J., and Bollyky, P.L. (2019). Interactions between Bacteriophage, Bacteria, and the Mammalian Immune System. Viruses, 11.","DOI":"10.3390\/v11010010"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/mBio.01874-17","article-title":"Bacteriophage Transcytosis Provides a Mechanism to Cross Epithelial Cell Layers","volume":"8","author":"Nguyen","year":"2017","journal-title":"mBio"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Aldars-Garc\u00eda, L., Gisbert, J.P., and Chaparro, M. (2021). Metabolomics Insights into Inflammatory Bowel Disease: A Comprehensive Review. Pharmaceuticals, 14.","DOI":"10.3390\/ph14111190"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1136\/gutjnl-2022-328048","article-title":"Faecal metabolome and its determinants in inflammatory bowel disease","volume":"72","author":"Vila","year":"2023","journal-title":"Gut"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1111\/jam.15319","article-title":"Metabolite and Transcriptome Analyses Revealed the Modulation of Fructo-Oligosaccharide on Ileum Metabolism of Taiping Chickens","volume":"132","author":"Ma","year":"2022","journal-title":"J. Appl. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"G535","DOI":"10.1152\/ajpgi.00008.2022","article-title":"Microbial Metabolites: Cause or Consequence in Gastrointestinal Disease?","volume":"322","author":"Fobofou","year":"2022","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Wang, G., McConn, B.R., Liu, D., Cline, M.A., and Gilbert, E.R. (2017). The Effects of Dietary Macronutrient Composition on Lipid Metabolism-Associated Factor Gene Expression in the Adipose Tissue of Chickens Are Influenced by Fasting and Refeeding. BMC Obes., 4.","DOI":"10.1186\/s40608-017-0150-8"},{"key":"ref_83","first-page":"27","article-title":"Evaluation of the Effect of Dietary Supplementation of Bacteriophage on Production Performance and Excreta Microflora of Commercial Broiler and Layer Chickens in Bangladesh","volume":"9","author":"Noor","year":"2020","journal-title":"MOJ Proteom. Bioinform."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"14391","DOI":"10.1038\/s41598-022-18663-1","article-title":"Effects of Bacteriophage Supplement on the Growth Performance, Microbial Population, and PGC-1\u03b1 and TLR4 Gene Expressions of Broiler Chickens","volume":"12","author":"Sarrami","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Sevilla-Navarro, S., Catal\u00e1-Gregori, P., and Marin, C. (2020). Salmonella Bacteriophage Diversity According to Most Prevalent Salmonella Serovars in Layer and Broiler Poultry Farms from Eastern Spain. Animals, 10.","DOI":"10.3390\/ani10091456"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Lorenzo-Rebenaque, L., Malik, D.J., Catal\u00e1-Gregori, P., Marin, C., and Sevilla-Navarro, S. (2021). In Vitro and In Vivo Gastrointestinal Survival of Non-Encapsulated and Microencapsulated Salmonella Bacteriophages: Implications for Bacteriophage Therapy in Poultry. Pharmaceuticals, 14.","DOI":"10.3390\/ph14050434"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"303","DOI":"10.21775\/cimb.040.303","article-title":"Bacteriophage Encapsulation Using Spray Drying for Phage Therapy","volume":"40","author":"Malik","year":"2021","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Ijaz, U.Z., Sivaloganathan, L., McKenna, A., Richmond, A., Kelly, C., Linton, M., Stratakos, A.C., Lavery, U., Elmi, A., and Wren, B.W. (2018). Comprehensive Longitudinal Microbiome Analysis of the Chicken Cecum Reveals a Shift from Competitive to Environmental Drivers and a Window of Opportunity for Campylobacter. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02452"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/nar\/gks808","article-title":"Evaluation of General 16S Ribosomal RNA Gene PCR Primers for Classical and Next-Generation Sequencing-Based Diversity Studies","volume":"41","author":"Klindworth","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_90","unstructured":"(2022, September 13). Babraham Bioinformatics FastQC A Quality Control Tool for High Throughput Sequence Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA Ribosomal RNA Gene Database Project: Improved Data Processing and Web-Based Tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"101971","DOI":"10.1016\/j.psj.2022.101971","article-title":"Research Note: Choice of Microbiota Database Affects Data Analysis and Interpretation in Chicken Cecal Microbiota","volume":"101","author":"Campos","year":"2022","journal-title":"Poult. Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s11240-017-1310-8","article-title":"A High-Throughput Flow Cytometry System for Early Screening of in Vitro Made Polyploids in Dendrobium Hybrids","volume":"132","author":"Grosso","year":"2018","journal-title":"Plant Cell Tissue Organ. Cult."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Garcia-Dominguez, X., Diretto, G., Frusciante, S., Vicente, J.S., and Marco-Jim\u00e9nez, F. (2020). Metabolomic Analysis Reveals Changes in Preimplantation Embryos Following Fresh or Vitrified Transfer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197116"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Yu, Y., Tan, P., Zhuang, Z., Wang, Z., Zhu, L., Qiu, R., and Xu, H. (2021). Untargeted Metabolomic Approach to Study the Serum Metabolites in Women with Polycystic Ovary Syndrome. BMC Med. Genom., 14.","DOI":"10.1186\/s12920-021-01058-y"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1021\/ac051495j","article-title":"Large-Scale Human Metabolomics Studies: A Strategy for Data (Pre-) Processing and Validation","volume":"78","author":"Bijlsma","year":"2006","journal-title":"Anal. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Greenacre, M., Mart\u00ednez-\u00c1lvaro, M., and Blasco, A. (2021). Compositional Data Analysis of Microbiome and Any-Omics Datasets: A Validation of the Additive Logratio Transformation. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.727398"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Rohart, F., Gautier, B., Singh, A., and Cao, K.-A.L. (2017). MixOmics: An R Package for \u2019omics Feature Selection and Multiple Data Integration. PLoS Comput. Biol., 13.","DOI":"10.1101\/108597"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/cem.2627","article-title":"Variable Influence on Projection (VIP) for Orthogonal Projections to Latent Structures (OPLS)","volume":"28","author":"Eriksson","year":"2014","journal-title":"J. Chemom."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Blasco, A. (2017). Bayesian Data Analysis for Animal Scientists: The Basics, Springer.","DOI":"10.1007\/978-3-319-54274-4"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/20\/15201\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:07:14Z","timestamp":1760130434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/20\/15201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,15]]},"references-count":100,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms242015201"],"URL":"https:\/\/doi.org\/10.3390\/ijms242015201","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,15]]}}}