{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:46:30Z","timestamp":1792179990934,"version":"4.4.0"},"reference-count":83,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["31660713"],"award-info":[{"award-number":["31660713"]}]},{"name":"National Natural Science Foundation of China","award":["81903168"],"award-info":[{"award-number":["81903168"]}]},{"name":"National Natural Science Foundation of China","award":["20212014"],"award-info":[{"award-number":["20212014"]}]},{"name":"National Natural Science Foundation of China","award":["20210035"],"award-info":[{"award-number":["20210035"]}]},{"name":"National Natural Science Foundation of China","award":["20220026"],"award-info":[{"award-number":["20220026"]}]},{"DOI":"10.13039\/501100019340","name":"The Nanning Science and Technology base Project","doi-asserted-by":"publisher","award":["31660713"],"award-info":[{"award-number":["31660713"]}],"id":[{"id":"10.13039\/501100019340","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019340","name":"The Nanning Science and Technology base Project","doi-asserted-by":"publisher","award":["81903168"],"award-info":[{"award-number":["81903168"]}],"id":[{"id":"10.13039\/501100019340","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019340","name":"The Nanning Science and Technology base Project","doi-asserted-by":"publisher","award":["20212014"],"award-info":[{"award-number":["20212014"]}],"id":[{"id":"10.13039\/501100019340","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019340","name":"The Nanning Science and Technology base Project","doi-asserted-by":"publisher","award":["20210035"],"award-info":[{"award-number":["20210035"]}],"id":[{"id":"10.13039\/501100019340","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019340","name":"The Nanning Science and Technology base Project","doi-asserted-by":"publisher","award":["20220026"],"award-info":[{"award-number":["20220026"]}],"id":[{"id":"10.13039\/501100019340","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Project of Bama Country for Talents in Science and Technology","award":["31660713"],"award-info":[{"award-number":["31660713"]}]},{"name":"The Project of Bama Country for Talents in Science and Technology","award":["81903168"],"award-info":[{"award-number":["81903168"]}]},{"name":"The Project of Bama Country for Talents in Science and Technology","award":["20212014"],"award-info":[{"award-number":["20212014"]}]},{"name":"The Project of Bama Country for Talents in Science and Technology","award":["20210035"],"award-info":[{"award-number":["20210035"]}]},{"name":"The Project of Bama Country for Talents in Science and Technology","award":["20220026"],"award-info":[{"award-number":["20220026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Salmonella typhimurium (S. typhimurium), a prevalent cause of foodborne infection, induces significant changes in the host transcriptome and metabolome. The lack of therapeutics with minimal or no side effects prompts the scientific community to explore alternative therapies. This study investigates the therapeutic potential of a probiotic mixture comprising Lactobacillus acidophilus (L. acidophilus 1.3251) and Lactobacillus plantarum (L. plantarum 9513) against S. typhimurium, utilizing transcriptome and metabolomic analyses, a novel approach that has not been previously documented. Twenty-four SPF-BALB\/c mice were divided into four groups: control negative group (CNG); positive control group (CPG); probiotic-supplemented non-challenged group (LAPG); and probiotic-supplemented Salmonella-challenged group (LAPST). An RNA-sequencing analysis of small intestinal (ileum) tissue revealed 2907 upregulated and 394 downregulated DEGs in the LAPST vs. CPG group. A functional analysis of DEGs highlighted their significantly altered gene ontology (GO) terms related to metabolism, gut integrity, cellular development, and immunity (p \u2264 0.05). The KEGG analysis showed that differentially expressed genes (DEGs) in the LAPST group were primarily involved in pathways related to gut integrity, immunity, and metabolism, such as MAPK, PI3K-Akt, AMPK, the tryptophan metabolism, the glycine, serine, and threonine metabolism, ECM\u2013receptor interaction, and others. Additionally, the fecal metabolic analysis identified 1215 upregulated and 305 downregulated metabolites in the LAPST vs. CPG group, implying their involvement in KEGG pathways including bile secretion, propanoate metabolism, arginine and proline metabolism, amino acid biosynthesis, and protein digestion and absorption, which are vital for maintaining barrier integrity, immunity, and metabolism. In conclusion, these findings suggest that the administration of a probiotic mixture improves immunity, maintains gut homeostasis and barrier integrity, and enhances metabolism in Salmonella infection.<\/jats:p>","DOI":"10.3390\/genes15040435","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:42:30Z","timestamp":1711892550000},"page":"435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Novel Synergistic Probiotic Intervention: Transcriptomic and Metabolomic Analysis Reveals Ameliorative Effects on Immunity, Gut Barrier, and Metabolism of Mice during Salmonella typhimurium Infection"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8922-5082","authenticated-orcid":false,"given":"Muhammad","family":"Junaid","sequence":"first","affiliation":[{"name":"Medical College, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Lu","sequence":"additional","affiliation":[{"name":"Medical College, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiang","family":"Li","sequence":"additional","affiliation":[{"name":"Medical College, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical College, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9879-2023","authenticated-orcid":false,"given":"Ahmad Ud","family":"Din","sequence":"additional","affiliation":[{"name":"Plants for Human Health Institute, North Carolina State University, 600 Laureate Way, Kannapolis, NC 28081, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongquan","family":"Qi","sequence":"additional","affiliation":[{"name":"Medical College, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xiong","sequence":"additional","affiliation":[{"name":"Guangxi Center for Animals Disease Control and Prevention, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Yan","sequence":"additional","affiliation":[{"name":"Medical College, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ehuwa, O., Jaiswal, A.K., and Jaiswal, S. (2021). Salmonella, food safety and food handling practices. Foods, 10.","DOI":"10.3390\/foods10050907"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.18683\/germs.2021.1244","article-title":"Salmonella spp. infection-a continuous threat worldwide","volume":"11","author":"Popa","year":"2021","journal-title":"Germs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/1758-2229.12628","article-title":"The metabolic pathways utilized by Salmonella typhimurium during infection of host cells","volume":"10","author":"Thompson","year":"2018","journal-title":"Environ. Microbiol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1089\/fpd.2019.2676","article-title":"The epidemiology of monophasic Salmonella typhimurium","volume":"17","author":"Sun","year":"2020","journal-title":"Foodborne Pathog. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1111\/jam.13459","article-title":"Lactobacillus paracasei metabolism of rice bran reveals metabolome associated with Salmonella typhimurium growth reduction","volume":"122","author":"Nealon","year":"2017","journal-title":"J. Appl. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"492","DOI":"10.2460\/javma.2002.221.492","article-title":"Animal sources of salmonellosis in humans","volume":"221","author":"Sanchez","year":"2002","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"438","DOI":"10.4103\/jehp.jehp_557_21","article-title":"Antibiotics at the crossroads\u2013Do we have any therapeutic alternatives to control the emergence and spread of antimicrobial resistance?","volume":"10","author":"Sannathimmappa","year":"2021","journal-title":"J. Educ. Health Promot."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.bbi.2020.04.014","article-title":"CD4+ CD25+ T Cells are Essential for Behavioral Effects of Lactobacillus rhamnosus JB-1 in Male BALB\/c mice","volume":"88","author":"Liu","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.eng.2020.06.026","article-title":"Lactobacillus plantarum CCFM8610 alleviates irritable bowel syndrome and prevents gut microbiota dysbiosis: A randomized, double-blind, placebo-controlled, pilot clinical trial","volume":"7","author":"Liu","year":"2021","journal-title":"Engineering"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature23480","article-title":"A randomized synbiotic trial to prevent sepsis among infants in rural India","volume":"548","author":"Panigrahi","year":"2017","journal-title":"Nature"},{"key":"ref_12","unstructured":"Michael, P., and Shivshetty, N. (2024, March 26). Chapter-5 Probiotics. Available online: https:\/\/www.researchgate.net\/profile\/Neelesh-Maurya\/publication\/374750375."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12934-017-0691-z","article-title":"Beneficial effects on host energy metabolism of short-chain fatty acids and vitamins produced by commensal and probiotic bacteria","volume":"16","author":"LeBlanc","year":"2017","journal-title":"Microb. Cell Factories"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"s51","DOI":"10.1079\/BJN2002629","article-title":"Probiotics and intestinal health effects: A clinical perspective","volume":"88","author":"Marteau","year":"2002","journal-title":"Br. J. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1017\/S0029665110001710","article-title":"Immune-stimulating effects of lactic acid bacteria in vivo and in vitro","volume":"69","author":"Elmadfa","year":"2010","journal-title":"Proc. Nutr. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101409","DOI":"10.1016\/j.aqrep.2022.101409","article-title":"Dietary effect of Lactobacillus plantarum (TISTR 912) on digestive enzyme activity, growth performance, immune response, and disease resistance of black sharkminnow (Labeo chrysophekadion) against Aeromonas hydrophila infection","volume":"27","author":"Keereelang","year":"2022","journal-title":"Aquac. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kwoji, I.D., Aiyegoro, O.A., Okpeku, M., and Adeleke, M.A. (2021). Multi-strain probiotics: Synergy among isolates enhances biological activities. Biology, 10.","DOI":"10.3390\/biology10040322"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100905","DOI":"10.1016\/j.aqrep.2021.100905","article-title":"Multi-strain probiotics: Functions, effectiveness and formulations for aquaculture applications","volume":"21","author":"Puvanasundram","year":"2021","journal-title":"Aquac. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Tremblay, A., Xu, X., Colee, J., and Tompkins, T.A. (2021). Efficacy of a multi-strain probiotic formulation in pediatric populations: A comprehensive review of clinical studies. Nutrients, 13.","DOI":"10.3390\/nu13061908"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s12602-017-9264-z","article-title":"Lactobacillus plantarum and its probiotic and food potentialities","volume":"9","author":"Seddik","year":"2017","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1756284820971201","DOI":"10.1177\/1756284820971201","article-title":"Lactobacillus acidophilus LB: A useful pharmabiotic for the treatment of digestive disorders","volume":"13","year":"2020","journal-title":"Ther. Adv. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1126\/science.aad8588","article-title":"Lactobacillus plantarum strain maintains growth of infant mice during chronic undernutrition","volume":"351","author":"Schwarzer","year":"2016","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1186\/s13054-018-2209-4","article-title":"Can probiotics be an alternative to chlorhexidine for oral care in the mechanically ventilated patient? A multicentre, prospective, randomised controlled open trial","volume":"22","author":"Klarin","year":"2018","journal-title":"Crit. Care"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.3389\/fimmu.2020.01428","article-title":"Probiotics and probiotic-derived functional factors\u2014Mechanistic insights into applications for intestinal homeostasis","volume":"11","author":"Yan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101323","DOI":"10.1016\/j.psj.2021.101323","article-title":"Effects of Lactobacillus acidophilus on the growth performance, immune response, and intestinal barrier function of broiler chickens challenged with Escherichia coli O157","volume":"100","author":"Wu","year":"2021","journal-title":"Poult. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1039\/C9FO02935D","article-title":"Identification of the key physiological characteristics of Lactobacillus plantarum strains for ulcerative colitis alleviation","volume":"11","author":"Liu","year":"2020","journal-title":"Food Funct."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.cell.2018.08.041","article-title":"Personalized gut mucosal colonization resistance to empiric probiotics is associated with unique host and microbiome features","volume":"174","author":"Zmora","year":"2018","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.chom.2018.11.002","article-title":"Microbiota-derived lactate accelerates intestinal stem-cell-mediated epithelial development","volume":"24","author":"Lee","year":"2018","journal-title":"Cell Host"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev-immunol-070119-115104","article-title":"Interaction between the microbiota, epithelia, and immune cells in the intestine","volume":"38","author":"Kayama","year":"2020","journal-title":"Annu. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jare.2021.06.012","article-title":"Protective effects of different Bacteroides vulgatus strains against lipopolysaccharide-induced acute intestinal injury, and their underlying functional genes","volume":"36","author":"Wang","year":"2022","journal-title":"J. Adv. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lowe, R., Shirley, N., Bleackley, M., Dolan, S., and Shafee, T. (2017). Transcriptomics technologies. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005457"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e03399-20","DOI":"10.1128\/mBio.03399-20","article-title":"In vivo transcriptome of Lactobacillus acidophilus and colonization impact on murine host intestinal gene expression","volume":"12","author":"Goh","year":"2021","journal-title":"mBio"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1038\/ismej.2010.61","article-title":"Convergence in probiotic Lactobacillus gut-adaptive responses in humans and mice","volume":"4","author":"Marco","year":"2010","journal-title":"ISME J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.7717\/peerj.32","article-title":"Associations between the human intestinal microbiota, Lactobacillus rhamnosus GG and serum lipids indicated by integrated analysis of high-throughput profiling data","volume":"1","author":"Lahti","year":"2013","journal-title":"PeerJ"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1016\/j.csbj.2022.03.038","article-title":"Gut microbial metabolome in inflammatory bowel disease: From association to therapeutic perspectives","volume":"20","author":"Li","year":"2022","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1007\/s42770-023-01060-9","article-title":"Comparison of the effects of probiotic strains (Lactobacillus gasseri, Lactiplantibacillus plantarum, Lactobacillus acidophilus, and Limosilactobacillus fermentum) isolated from human and food products on the immune response of CT26 tumor\u2013bearing mice","volume":"54","author":"Hatami","year":"2023","journal-title":"Braz. J. Microbiol."},{"key":"ref_37","first-page":"431","article-title":"Probiotic features of Lactobacillus plantarum mutant strains","volume":"96","author":"Bove","year":"2012","journal-title":"J. Appl. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/1574-6968.12293","article-title":"The life history of Lactobacillus acidophilus as a probiotic: A tale of revisionary taxonomy, misidentification and commercial success","volume":"349","author":"Bull","year":"2013","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_39","unstructured":"Baiandina, I., Kuleshova, O., and Krivenko, O. (2024, March 26). Light perception in Beroidae ctenophores: Evidence from laboratory experiments and genomics data. Available online: https:\/\/elibrary.ru\/item.asp?id=49238119."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1158\/1538-7445.AM2022-3566","article-title":"Sensitizing potential of a novel stimulated and haptenized vaccine in immunotherapy resistant metastatic colorectal cancer","volume":"82","author":"Richard","year":"2022","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13045-023-01442-4","article-title":"Myeloid-like tumor hybrid cells in bone marrow promote progression of prostate cancer bone metastasis","volume":"16","author":"Ye","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.2147\/CCID.S413887","article-title":"Transcriptome Analysis Identifies Biomarkers for the Diagnosis and Management of Psoriasis Complicated with Depression","volume":"16","author":"Xia","year":"2023","journal-title":"Clin. Cosmet. Investig. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1093\/jaoacint\/qsaa063","article-title":"A validated real-time PCR method for the specific identification of probiotic strain Lactobacillus rhamnosus GG (ATCC 53103)","volume":"103","author":"Shehata","year":"2020","journal-title":"J. AOAC Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e13307","DOI":"10.1111\/aji.13307","article-title":"Correlation of fecal metabolomics and gut microbiota in mice with endometriosis","volume":"84","author":"Ni","year":"2020","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jpba.2017.02.008","article-title":"Variations in gut microbiota and fecal metabolic phenotype associated with depression by 16S rRNA gene sequencing and LC\/MS-based metabolomics","volume":"138","author":"Yu","year":"2017","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Huang, F., Fu, M., Li, J., Chen, L., Feng, K., Huang, T., and Cai, Y.-D. (2023). Analysis and prediction of protein stability based on interaction network, gene ontology, and kegg pathway enrichment scores. Biochim. Et Biophys. Acta (BBA)-Proteins Proteom., 1871.","DOI":"10.1016\/j.bbapap.2023.140889"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/nm.4102","article-title":"CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands","volume":"22","author":"Lamas","year":"2016","journal-title":"Nat. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhang, H., Pan, S., Zhang, K., Michiels, J., Zeng, Q., Ding, X., Wang, J., Peng, H., Bai, J., and Xuan, Y. (2020). Impact of dietary manganese on intestinal barrier and inflammatory response in broilers challenged with Salmonella typhimurium. Microorganisms, 8.","DOI":"10.3390\/microorganisms8050757"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Taylor, S.J., and Winter, S.E. (2020). Salmonella finds a way: Metabolic versatility of Salmonella enterica serovar typhimurium in diverse host environments. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008540"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, S., Fischer, J., Ganesan, R., Hos, N.J., Cildir, G., Wolke, M., Pessia, A., Frommolt, P., Desiderio, V., and Velagapudi, V. (2021). Salmonella typhimurium impairs glycolysis-mediated acidification of phagosomes to evade macrophage defense. PLoS Pathog., 17.","DOI":"10.1101\/2021.01.14.426635"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Qin, X., Yang, M., Cai, H., Liu, Y., Gorris, L., Aslam, M.Z., Jia, K., Sun, T., Wang, X., and Dong, Q. (2022). Antibiotic Resistance of Salmonella typhimurium Monophasic Variant 1,4,[5],12:i:-in China: A Systematic Review and Meta-Analysis. Antibiotics, 11.","DOI":"10.3390\/antibiotics11040532"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Latif, A., Shehzad, A., Niazi, S., Zahid, A., Ashraf, W., Iqbal, M.W., Rehman, A., Riaz, T., Aadil, R.M., and Khan, I.M. (2023). Probiotics: Mechanism of action, health benefits and their application in food industries. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1216674"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Mazziotta, C., Tognon, M., Martini, F., Torreggiani, E., and Rotondo, J.C. (2023). Probiotics mechanism of action on immune cells and beneficial effects on human health. Cells, 12.","DOI":"10.3390\/cells12010184"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wolfe, W., Xiang, Z., Yu, X., Li, P., Chen, H., Yao, M., Fei, Y., Huang, Y., Yin, Y., and Xiao, H. (2023). The challenge of applications of probiotics in gastrointestinal diseases. Adv. Gut Microbiome Res., 2023.","DOI":"10.1155\/2023\/1984200"},{"key":"ref_55","first-page":"787796Satin","article-title":"An update on the use and investigation of probiotics in health and disease","volume":"62","author":"Sherman","year":"2013","journal-title":"Gut"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e01651-22","DOI":"10.1128\/spectrum.01651-22","article-title":"Probiotics (Lactobacillus plantarum HNU082) supplementation relieves ulcerative colitis by affecting intestinal barrier functions, immunity-related gene expression, gut microbiota, and metabolic pathways in mice","volume":"10","author":"Wu","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1007\/s00253-021-11099-z","article-title":"Modulation of the immune response and metabolism in germ-free rats colonized by the probiotic Lactobacillus salivarius LI01","volume":"105","author":"Xia","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"152","DOI":"10.4161\/gmic.27877","article-title":"In vivo gut transcriptome responses to Lactobacillus rhamnosus GG and Lactobacillus acidophilus in neonatal gnotobiotic piglets","volume":"5","author":"Kumar","year":"2014","journal-title":"Gut Microbes"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.gene.2019.02.068","article-title":"Transcriptome modulation by in ovo delivered Lactobacillus synbiotics in a range of chicken tissues","volume":"698","author":"Dunislawska","year":"2019","journal-title":"Gene"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Memon, F.U., Yang, Y., Leghari, I.H., Lv, F., Soliman, A.M., Zhang, W., and Si, H. (2021). Transcriptome analysis revealed ameliorative effects of Bacillus based probiotic on immunity, gut barrier system, and metabolism of chicken under an experimentally induced Eimeria tenella infection. Genes, 12.","DOI":"10.3390\/genes12040536"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11589","DOI":"10.1038\/srep11589","article-title":"Metabolome progression during early gut microbial colonization of gnotobiotic mice","volume":"5","author":"Marcobal","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.jaci.2017.02.011","article-title":"Correlation between early-life regulation of the immune system by microbiota and allergy development","volume":"139","author":"Gensollen","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14631","DOI":"10.1096\/fj.202001428R","article-title":"Simulated microgravity suppresses MAPK pathway-mediated innate immune response to bacterial infection and induces gut microbiota dysbiosis","volume":"34","author":"Wang","year":"2020","journal-title":"FASEB J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.it.2005.11.007","article-title":"MAP kinase kinase kinases and innate immunity","volume":"27","author":"Symons","year":"2006","journal-title":"Trends Immunol."},{"key":"ref_65","first-page":"994","article-title":"Probiotic Lactobacillus casei activates innate immunity via NF-\u03baB and p38 MAP kinase signaling pathways","volume":"8","author":"Kim","year":"2006","journal-title":"Microbes"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"739","DOI":"10.3920\/BM2015.0181","article-title":"The different effects of probiotics treatment on Salmonella-induced interleukin-8 response in intestinal epithelia cells via PI3K\/Akt and NOD2 expression","volume":"7","author":"Huang","year":"2016","journal-title":"Benef. Microbes"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/jcp.31016","article-title":"Lactobacillus plantarum postbiotics trigger AMPK-dependent autophagy to suppress Salmonella intracellular infection and NLRP3 inflammasome activation","volume":"238","author":"Wu","year":"2023","journal-title":"J. Cell. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"991","DOI":"10.2174\/1566524023666221014140817","article-title":"FoxO3 Regulates the Progress and Development of Aging and Aging-Related Diseases","volume":"23","author":"Chang","year":"2023","journal-title":"Curr. Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"6850","DOI":"10.1111\/febs.15776","article-title":"A guide to the composition and functions of the extracellular matrix","volume":"288","author":"Karamanos","year":"2021","journal-title":"FEBS J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"110046","DOI":"10.1016\/j.cellsig.2021.110046","article-title":"Focal adhesion dynamics in cellular function and disease","volume":"85","author":"Mishra","year":"2021","journal-title":"Cell. Signal."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1083\/jcb.201106011","article-title":"Impenetrable barriers or entry portals? The role of cell\u2013cell adhesion during infection","volume":"195","author":"Bonazzi","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1007\/s00726-022-03179-9","article-title":"Tryptophan regulates bile and nitrogen metabolism in two pig gut lactobacilli species in vitro based on metabolomics study","volume":"54","author":"Wu","year":"2022","journal-title":"Amino Acids"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Zhang, W., Zhang, Y., Li, Y., Ma, D., Zhang, H., and Kwok, L.-Y. (2022). Lacticaseibacillus rhamnosus Probio-M9-driven mouse mammary tumor-inhibitory effect is accompanied by modulation of host gut microbiota, immunity, and serum metabolome. Nutrients, 15.","DOI":"10.21203\/rs.3.rs-2053698\/v1"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Lin, C.-C., Huang, W.-C., Su, C.-H., Lin, W.-D., Wu, W.-T., Yu, B., and Hsu, Y.-M. (2020). Effects of multi-strain probiotics on immune responses and metabolic balance in helicobacter pylori-infected mice. Nutrients, 12.","DOI":"10.3390\/nu12082476"},{"key":"ref_75","first-page":"2000461","article-title":"An insight into the roles of dietary tryptophan and its metabolites in intestinal inflammation and inflammatory bowel disease","volume":"65","author":"Li","year":"2021","journal-title":"Mol. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e01188-18","DOI":"10.1128\/mBio.01188-18","article-title":"Branching out: Alterations in bacterial physiology and virulence due to branched-chain amino acid deprivation","volume":"9","author":"Kaiser","year":"2018","journal-title":"mBio"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Shao, Y., Zhen, W., Guo, F., Hu, Z., Zhang, K., Kong, L., Guo, Y., and Wang, Z. (2022). Pretreatment with probiotics Enterococcus faecium NCIMB 11181 attenuated Salmonella typhimurium-induced gut injury through modulating intestinal microbiome and immune responses with barrier function in broiler chickens. J. Anim. Sci. Biotechnol., 13.","DOI":"10.1186\/s40104-022-00765-5"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Wang, G., Huang, S., Cai, S., Yu, H., Wang, Y., Zeng, X., and Qiao, S. (2020). Lactobacillus reuteri ameliorates intestinal inflammation and modulates gut microbiota and metabolic disorders in dextran sulfate sodium-induced colitis in mice. Nutrients, 12.","DOI":"10.3390\/nu12082298"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1007\/s12602-022-09923-7","article-title":"Effects of dietary supplementation with Lactobacillus acidophilus and Bacillus subtilis on mucosal immunity and intestinal barrier are associated with its modulation of gut metabolites and microbiota in late-phase laying hens","volume":"15","author":"Chen","year":"2023","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5303","DOI":"10.1007\/s00018-021-03828-4","article-title":"Arginine-dependent immune responses","volume":"78","author":"Reith","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1017\/S0007114521004566","article-title":"Important roles of amino acids in immune responses","volume":"127","author":"Li","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"574","DOI":"10.3390\/nu3050574","article-title":"Dietary proteins as determinants of metabolic and physiologic functions of the gastrointestinal tract","volume":"3","author":"Luhovyy","year":"2011","journal-title":"Nutrients"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zhao, D.-D., Gai, Y.-D., Li, C., Fu, Z.-Z., Yin, D.-Q., Xie, M., Dai, J.-Y., Wang, X.-X., Li, Y.-X., and Wu, G.-F. (2023). Dietary taurine effect on intestinal barrier function, colonic microbiota and metabolites in weanling piglets induced by LPS. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1259133"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/4\/435\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:21:03Z","timestamp":1760106063000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/4\/435"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":83,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["genes15040435"],"URL":"https:\/\/doi.org\/10.3390\/genes15040435","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,29]]}}}