{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:57:53Z","timestamp":1775800673531,"version":"3.50.1"},"reference-count":74,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This study investigates the gut microbiome and metabolome of asthma patients treated with inhaled corticosteroids (ICS), some of whom experience adverse side effects. We analyzed stool samples from 24 participants, divided into three cohorts: asthma patients with side effects, those without, and healthy controls. Using next-generation sequencing and LC-MS\/MS metabolomics, we identified significant differences in bacterial species and metabolites. Multi-Omics Factor Analysis (MOFA) and Global Sensitivity Analysis-Partial Rank Correlation Coefficient (GSA-PRCC) provided insights into key contributors to side effects, such as tryptophan depletion and altered linolenate and glucose-1-phosphate levels. The study proposes dietary or probiotic interventions to mitigate side effects. Despite the limited sample size, these findings provide a basis for personalized asthma management approaches. Further studies are required to confirm initial fundings.<\/jats:p>","DOI":"10.1515\/jib-2024-0062","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T11:57:34Z","timestamp":1750679854000},"source":"Crossref","is-referenced-by-count":0,"title":["Metagenome and metabolome study on inhaled corticosteroids in asthma patients with side effects"],"prefix":"10.1515","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8293-774X","authenticated-orcid":false,"given":"Igor","family":"Goryanin","sequence":"first","affiliation":[{"name":"School of Informatics , University of Edinburgh , Edinburgh , UK"},{"name":"Okinawa Institute Science and Technology , Okinawa , Japan"},{"name":"KGDiscovery LTD , Edinburgh , UK"},{"name":"Kyrgyz State Medical Academy Named After I.K. Akhunbaev , Bishkek , Kyrgyzstan"},{"name":"MMWR LTD , Edinburgh , UK"}]},{"given":"Anatoly","family":"Sorokin","sequence":"additional","affiliation":[{"name":"Okinawa Institute Science and Technology , Okinawa , Japan"},{"name":"KGDiscovery LTD , Edinburgh , UK"}]},{"given":"Meder","family":"Seitov","sequence":"additional","affiliation":[{"name":"KGDiscovery LTD , Edinburgh , UK"},{"name":"Kyrgyz State Medical Academy Named After I.K. Akhunbaev , Bishkek , Kyrgyzstan"}]},{"given":"Berik","family":"Emilov","sequence":"additional","affiliation":[{"name":"KGDiscovery LTD , Edinburgh , UK"},{"name":"Kyrgyz State Medical Academy Named After I.K. Akhunbaev , Bishkek , Kyrgyzstan"}]},{"given":"Muktarbek","family":"Iskakov","sequence":"additional","affiliation":[{"name":"Kyrgyz State Medical Academy Named After I.K. Akhunbaev , Bishkek , Kyrgyzstan"}]},{"given":"Irina","family":"Goryanin","sequence":"additional","affiliation":[{"name":"MMWR LTD , Edinburgh , UK"}]},{"given":"Batyr","family":"Osmonov","sequence":"additional","affiliation":[{"name":"KGDiscovery LTD , Edinburgh , UK"},{"name":"Kyrgyz State Medical Academy Named After I.K. Akhunbaev , Bishkek , Kyrgyzstan"}]}],"member":"374","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"2026041005053822025_j_jib-2024-0062_ref_001","doi-asserted-by":"crossref","unstructured":"Frati, F, Salvatori, C, Incorvaia, C, Bellucci, A, Di Cara, G, Marcucci, F, et al.. The role of the microbiome in asthma: the gut\u2013lung Axis. Int J Mol Sci 2019;20:123. https:\/\/doi.org\/10.3390\/ijms20010123.","DOI":"10.3390\/ijms20010123"},{"key":"2026041005053822025_j_jib-2024-0062_ref_002","doi-asserted-by":"crossref","unstructured":"Logo\u0144, K, \u015awirkosz, G, Nowak, M, Wrze\u015bniewska, M, Szczygie\u0142, A, Gomu\u0142ka, K. The role of the microbiome in the pathogenesis and treatment of asthma. Biomedicines 2023;11:1618. https:\/\/doi.org\/10.3390\/biomedicines11061618.","DOI":"10.3390\/biomedicines11061618"},{"key":"2026041005053822025_j_jib-2024-0062_ref_003","doi-asserted-by":"crossref","unstructured":"Enaud, R, Prevel, R, Ciarlo, E, Beaufils, F, Wie\u00ebrs, G, Guery, B, et al.. The gut-lung Axis in health and respiratory diseases: a place for inter-organ and inter-Kingdom Crosstalks. Front Cell Infect Microbiol 2020;10:9. https:\/\/doi.org\/10.3389\/fcimb.2020.00009.","DOI":"10.3389\/fcimb.2020.00009"},{"key":"2026041005053822025_j_jib-2024-0062_ref_004","doi-asserted-by":"crossref","unstructured":"Zhou, A, Lei, Y, Tang, L, Hu, S, Yang, M, Wu, L, et al.. Gut microbiota: the emerging link to lung homeostasis and disease. J Bacteriol 2021;203:e00454\u201320. https:\/\/doi.org\/10.1128\/JB.00454-20.","DOI":"10.1128\/JB.00454-20"},{"key":"2026041005053822025_j_jib-2024-0062_ref_005","doi-asserted-by":"crossref","unstructured":"Dumas, A, Bernard, L, Poquet, Y, Lugo-Villarino, G, Neyrolles, O. The role of the lung microbiota and the gut-lung axis in respiratory infectious diseases. Cell Microbiol 2018;20:e12966. https:\/\/doi.org\/10.1111\/cmi.12966.","DOI":"10.1111\/cmi.12966"},{"key":"2026041005053822025_j_jib-2024-0062_ref_006","unstructured":"Heijink, IH, Pouwels, SD, Leijendekker, C, de Bruin, HG, Zijlstra, GJ, van der Vaart, H, et al.. Cigarette smoke impairs airway epithelial barrier function and cell-cell contact recovery. Eur Respir J 2015;45:394\u2013403."},{"key":"2026041005053822025_j_jib-2024-0062_ref_075","doi-asserted-by":"crossref","unstructured":"Keir, HR, Contoli, M, Chalmers, JD. Inhaled corticosteroids and the lung microbiome in COPD. Biomedicines 2021;9:1312. https:\/\/doi.org\/10.3390\/biomedicines9101312.","DOI":"10.3390\/biomedicines9101312"},{"key":"2026041005053822025_j_jib-2024-0062_ref_008","doi-asserted-by":"crossref","unstructured":"Sze, MA, Tsuruta, M, Yang, SW, Oh, Y, Man, SFP, Hogg, JC, et al.. Changes in the bacterial microbiota in gut, blood, and lungs following acute LPS instillation into mice lungs. PLoS One 2015;10:e0140990.","DOI":"10.1371\/journal.pone.0111228"},{"key":"2026041005053822025_j_jib-2024-0062_ref_009","doi-asserted-by":"crossref","unstructured":"Man, WH, de Steenhuijsen Piters, WAA, Bogaert, D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat Rev Microbiol 2017;15:259\u201370. https:\/\/doi.org\/10.1038\/nrmicro.2017.14.","DOI":"10.1038\/nrmicro.2017.14"},{"key":"2026041005053822025_j_jib-2024-0062_ref_010","doi-asserted-by":"crossref","unstructured":"Hilty, M, Burke, C, Pedro, H, Cardenas, P, Bush, A, Bossley, C, et al.. Disordered microbial communities in asthmatic airways. PLoS One 2010;5:e8578. https:\/\/doi.org\/10.1371\/journal.pone.0008578.","DOI":"10.1371\/journal.pone.0008578"},{"key":"2026041005053822025_j_jib-2024-0062_ref_011","doi-asserted-by":"crossref","unstructured":"Marri, PR, Stern, DA, Wright, AL, Billheimer, D, Martinez, FD. Asthma-associated differences in microbial composition of induced sputum. J Allergy Clin Immunol 2013;131:346\u201352.e3. https:\/\/doi.org\/10.1016\/j.jaci.2012.11.013.","DOI":"10.1016\/j.jaci.2012.11.013"},{"key":"2026041005053822025_j_jib-2024-0062_ref_012","doi-asserted-by":"crossref","unstructured":"Wang, Z, Singh, R, Miller, BE, Tal-Singer, R, Van Horn, S, Tomsho, L, et al.. Lung microbiome dynamics in COPD exacerbations. Eur Respir J 2016;47:1082\u201392. https:\/\/doi.org\/10.1183\/13993003.01406-2015.","DOI":"10.1183\/13993003.01406-2015"},{"key":"2026041005053822025_j_jib-2024-0062_ref_013","doi-asserted-by":"crossref","unstructured":"Goryanin, I, Sorokin, A, Vasieva, O. Using ASAR for analysis of electrogenic and human gut microbial communities. In Proceedings of the 13th international joint conference on biomedical engineering systems and technologies - bioinformatics. SciTePress - Science and Technology Publications; 2020, vol. III, 253\u20139 pp. https:\/\/doi.org\/10.5220\/0009193602530259.","DOI":"10.5220\/0009193602530259"},{"key":"2026041005053822025_j_jib-2024-0062_ref_014","unstructured":"https:\/\/www.asthmacontroltest.com\/."},{"key":"2026041005053822025_j_jib-2024-0062_ref_015","doi-asserted-by":"crossref","unstructured":"Moscato, G, Godnic-Cvar, J, Maestrelli, P, Malo, J, Burge, P, Coifman, R. Statement on self-monitoring of peak expiratory flows in the investigation of occupational asthma. Eur Respir J 1995;8:1605\u201310. https:\/\/doi.org\/10.1183\/09031936.95.08091605. Printed in UK \u2013 all rights reserved).","DOI":"10.1183\/09031936.95.08091605"},{"key":"2026041005053822025_j_jib-2024-0062_ref_016","doi-asserted-by":"crossref","unstructured":"Mariotti, F, Collarini, S, Vezzoli, S, Acerbi, D, Scuri, M, Kuna, P. Effect of antistatic AeroChamber Plus\u00ae Flow-Vu\u00ae spacer on the systemic bioavailability of CHF5993 a novel triple pMDI. Eur Respir J 2016;48:PA964. https:\/\/doi.org\/10.1183\/13993003.congress-2016.PA964.","DOI":"10.1183\/13993003.congress-2016.PA964"},{"key":"2026041005053822025_j_jib-2024-0062_ref_017","doi-asserted-by":"crossref","unstructured":"Lauber, CL, Zhou, N, Gordon, JI, Knight, R, Fierer, N. Effect of storage conditions on the assessment of bacterial community structure in soil and human-associated samples. FEMS Microbiol Lett 2010;307:80\u20136. https:\/\/doi.org\/10.1111\/j.1574-6968.2010.01965.x.","DOI":"10.1111\/j.1574-6968.2010.01965.x"},{"key":"2026041005053822025_j_jib-2024-0062_ref_018","doi-asserted-by":"crossref","unstructured":"Franzosa, EA, Morgan, XC, Segata, N, Waldron, L, Reyes, J, Earl, AM, et al.. Relating the metatranscriptome and metagenome of the human gut. Proc Natl Acad Sci 2014;111:E2329\u201338. https:\/\/doi.org\/10.1073\/pnas.1319284111.","DOI":"10.1073\/pnas.1319284111"},{"key":"2026041005053822025_j_jib-2024-0062_ref_019","doi-asserted-by":"crossref","unstructured":"Chen, Y, Chen, Y, Shi, C, Huang, Z, Zhang, Y, Li, S, et al.. SOAPnuke: a MapReduce acceleration-supported software for integrated quality control and preprocessing of high-throughput sequencing data. Gigascience 2018;7:1\u20136, PMID: 29220494. PMCID: PMC5788068. https:\/\/doi.org\/10.1093\/gigascience\/gix120.","DOI":"10.1093\/gigascience\/gix120"},{"key":"2026041005053822025_j_jib-2024-0062_ref_020","doi-asserted-by":"crossref","unstructured":"Ewing, B, Green, P. Base-calling of automated sequencer traces using Phred. II. Error probabilities. Genome Res 1998;8:186\u201394. https:\/\/doi.org\/10.1101\/gr.8.3.186.","DOI":"10.1101\/gr.8.3.186"},{"key":"2026041005053822025_j_jib-2024-0062_ref_021","doi-asserted-by":"crossref","unstructured":"Ewing, B, Hillier, L, Wendl, MC, Green, P. Base-calling of automated sequencer traces using Phred. I. Accuracy assessment. Genome Res 1998;8:175\u201385. https:\/\/doi.org\/10.1101\/gr.8.3.175.","DOI":"10.1101\/gr.8.3.175"},{"key":"2026041005053822025_j_jib-2024-0062_ref_022","doi-asserted-by":"crossref","unstructured":"MacManes, MD. On the optimal trimming of high-throughput mRNA sequence data. Front Genet 2014;5:13. https:\/\/doi.org\/10.3389\/fgene.2014.00013.","DOI":"10.3389\/fgene.2014.00013"},{"key":"2026041005053822025_j_jib-2024-0062_ref_023","doi-asserted-by":"crossref","unstructured":"Di Guida, R, Engel, J, Allwood, JW, Weber, RJM, Jones, MR, Sommer, U, et al.. Non-targeted UHPLC-MS metabolomic data processing methods: a comparative investigation of normalization, missing value imputation, transformation, and scaling. Metabolomics 2016;12:93. https:\/\/doi.org\/10.1007\/s11306-016-1030-9.","DOI":"10.1007\/s11306-016-1030-9"},{"key":"2026041005053822025_j_jib-2024-0062_ref_024","unstructured":"Xiao, JF, Zhou, B. Metabolomics and integrated metabolomics for the evaluation of metabolic profiling and biomarker 2015."},{"key":"2026041005053822025_j_jib-2024-0062_ref_025","doi-asserted-by":"crossref","unstructured":"Want, EJ, Wilson, ID, Gika, H, Theodoridis, G, Plumb, RS, Shockcor, J, et al.. Global metabolic profiling procedures for urine using UPLC-MS. Nat Protoc 2010;5:1005\u201318. https:\/\/doi.org\/10.1038\/nprot.2010.50.","DOI":"10.1038\/nprot.2010.50"},{"key":"2026041005053822025_j_jib-2024-0062_ref_026","doi-asserted-by":"crossref","unstructured":"Orakov, AN, Sakenova, NK, Sorokin, A, Goryanin, I. ASAR: visual analysis of metagenomes in R. Bioinformatics 2018;34:1404\u20135. https:\/\/doi.org\/10.1093\/bioinformatics\/btx775.","DOI":"10.1093\/bioinformatics\/btx775"},{"key":"2026041005053822025_j_jib-2024-0062_ref_027","doi-asserted-by":"crossref","unstructured":"Orakov, A, Sakenova, N, Goryanin, I, Sorokin, A. ASAR database: an R tool for visual analysis and storage of metagenomes. In Proceedings of the 11th international joint conference on biomedical engineering systems and technologies (BIOSTEC 2018) \u2013 Bioinformatics. Madeira, Portugal; 2018, vol. III, 196\u2013200 pp. https:\/\/doi.org\/10.5220\/0006722801960200.","DOI":"10.5220\/0006722801960200"},{"key":"2026041005053822025_j_jib-2024-0062_ref_028","unstructured":"Vasieva, O, Sorokin, A, Murzabaev, M, Babiak, P. Goryanin, I. Study on the analysis of personal gut microbiomes. J Comput Sci Syst Biol 2019."},{"key":"2026041005053822025_j_jib-2024-0062_ref_029","unstructured":"Vasieva, O. I goryanin \u2013 the gut microbiome versus COVID-19. J Comput Sci Syst Biol 2021."},{"key":"2026041005053822025_j_jib-2024-0062_ref_030","doi-asserted-by":"crossref","unstructured":"Szydlowski, L, Ehlich, J, Szczerbiak, P, Shibata, N. I Goryanin Novel species identification and deep functional annotation of electrogenic biofilms, selectively enriched in a microbial fuel cell array. Front Microbiol 2022;13:951044. https:\/\/doi.org\/10.3389\/fmicb.2022.951044.","DOI":"10.3389\/fmicb.2022.951044"},{"key":"2026041005053822025_j_jib-2024-0062_ref_031","unstructured":"Goryanin, I, Sorokin, A, Seitov, M, Emilov, B, Iskakov, M, Osmonov, B. Study on Inhaled steroids side effects. Kyrg Repub Healthc 2023;4 Preprints."},{"key":"2026041005053822025_j_jib-2024-0062_ref_032","doi-asserted-by":"crossref","unstructured":"Sorokin, A, Goryanin, I. FBA-PRCC partial rank correlation coefficient (PRCC) global sensitivity analysis (GSA) in application to constraint-based models. Biomolecules 2023;13:500\u201310. https:\/\/doi.org\/10.3390\/biom13030500.","DOI":"10.3390\/biom13030500"},{"key":"2026041005053822025_j_jib-2024-0062_ref_033","doi-asserted-by":"crossref","unstructured":"Manichanh, C, Borruel, N, Casellas, F, Guarner, F. The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol 2012;9:599\u2013608. https:\/\/doi.org\/10.1038\/nrgastro.2012.152.","DOI":"10.1038\/nrgastro.2012.152"},{"key":"2026041005053822025_j_jib-2024-0062_ref_034","doi-asserted-by":"crossref","unstructured":"Love, MI, Huber, W, Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014;15:550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026041005053822025_j_jib-2024-0062_ref_035","doi-asserted-by":"crossref","unstructured":"Balmant, BD, Fonseca, DC, Prud\u00eancio, APA, Rocha, IM, Callado, L, Alves, JTM, et al.. Megamonas funiformis, plasma Zonulin, and Sodium intake affect C3 complement levels in inactive systemic lupus erythematosus. Nutrients 2023;15:1999. https:\/\/doi.org\/10.3390\/nu15081999.","DOI":"10.3390\/nu15081999"},{"key":"2026041005053822025_j_jib-2024-0062_ref_036","doi-asserted-by":"crossref","unstructured":"Galeana-Cadena, D, G\u00f3mez-Garc\u00eda, IA, Lopez-Salinas, KG, Irineo-Moreno, V, Jim\u00e9nez-Ju\u00e1rez, F, Tapia-Garc\u00eda, AR, et al.. Winds of change a tale of: asthma and microbiomeFront. Microbiol. Sec Infect Agents and Dis 2023:14\u20132023. https:\/\/doi.org\/10.3389\/fmicb.2023.1295215.","DOI":"10.3389\/fmicb.2023.1295215"},{"key":"2026041005053822025_j_jib-2024-0062_ref_037","doi-asserted-by":"crossref","unstructured":"Balmant, BD, Fonseca, DC, Prud\u00eancio, APA, Rocha, IM, Callado, L, Alves, JTM, et al.. Megamonas funiformis, plasma Zonulin, and Sodium intake affect C3 complement levels in Inactive systemic lupus erythematosus. Nutrients 2023;15:1999. https:\/\/doi.org\/10.3390\/nu15081999.","DOI":"10.3390\/nu15081999"},{"key":"2026041005053822025_j_jib-2024-0062_ref_038","doi-asserted-by":"crossref","unstructured":"Lian, FP, Zhang, F, Zhao, CM, Wang, XX, Bu, YJ, Cen, X, et al.. Gut microbiota regulation of T lymphocyte subsets during systemic lupus erythematosus. BMC Immunol 2024;25:41. https:\/\/doi.org\/10.1186\/s12865-024-00632-0.","DOI":"10.1186\/s12865-024-00632-0"},{"key":"2026041005053822025_j_jib-2024-0062_ref_039","unstructured":"Weber-D\u0105browska, B. Bacteriophages in the gastrointestinal tract and their implications. Gut Pathog 2023. https:\/\/gutpathogens.biomedcentral.com\/articles\/10.1186\/s13099-023-00473-2."},{"key":"2026041005053822025_j_jib-2024-0062_ref_040","doi-asserted-by":"crossref","unstructured":"Ogilvie, LA, Caplin, J, Dedi, C, Diston, D, Cheek, E, Bowler, L, et al.. Comparative (meta)genomic analysis and ecological profiling of human gut-specific bacteriophage \u03c6B124-14. PLoS One 2012;7:e35053. https:\/\/doi.org\/10.1371\/journal.pone.0035053.","DOI":"10.1371\/journal.pone.0035053"},{"key":"2026041005053822025_j_jib-2024-0062_ref_041","doi-asserted-by":"crossref","unstructured":"Sutton, TDS, Hill, C. Gut bacteriophage: current understanding and challenges. Front Endocrinol 2019;10:784. https:\/\/doi.org\/10.3389\/fendo.2019.00784.","DOI":"10.3389\/fendo.2019.00784"},{"key":"2026041005053822025_j_jib-2024-0062_ref_042","doi-asserted-by":"crossref","unstructured":"Benler, S, Yutin, N, Antipov, D, Rayko, M, Shmakov, S, Gussow, AB, et al.. Thousands of previously unknown phages discovered in whole-community human gut metagenomes. Microbiome 2021;9:78. https:\/\/doi.org\/10.1186\/s40168-021-01017-w.","DOI":"10.1186\/s40168-021-01017-w"},{"key":"2026041005053822025_j_jib-2024-0062_ref_043","doi-asserted-by":"crossref","unstructured":"Leal Rodr\u00edguez, C, Shah, SA, Rasmussen, MA, Thorsen, J, Boulund, U, Pedersen, CET, et al.. The infant gut virome is associated with preschool asthma risk independently of bacteria. Nat Med 2024;30:138\u201348. https:\/\/doi.org\/10.1038\/s41591-023-02685-x.","DOI":"10.1038\/s41591-023-02685-x"},{"key":"2026041005053822025_j_jib-2024-0062_ref_044","doi-asserted-by":"crossref","unstructured":"K\u00e4mpfer, P, McInroy, JA, Glaeser, SP. Chryseobacterium rhizoplanae sp. nov., isolated from the rhizoplane environment. Antonie Leeuwenhoek 2015;107:533\u20138. https:\/\/doi.org\/10.1007\/s10482-014-0349-3.","DOI":"10.1007\/s10482-014-0349-3"},{"key":"2026041005053822025_j_jib-2024-0062_ref_045","doi-asserted-by":"crossref","unstructured":"Valverde-Molina, J, Garc\u00eda-Marcos, L. Microbiome and asthma: microbial dysbiosis and the origins, phenotypes, persistence, and severity of asthma. Nutrients 2023;15:486. https:\/\/doi.org\/10.3390\/nu15030486.","DOI":"10.3390\/nu15030486"},{"key":"2026041005053822025_j_jib-2024-0062_ref_046","doi-asserted-by":"crossref","unstructured":"Argelaguet, R, Arnol, D, Bredikhin, D, Deloro, Y, Velten, B, Marioni, JC, et al.. MOFA+: a statistical framework for comprehensive integration of multi-modal single-cell data. Genome Biol 2020;21:1\u201317. https:\/\/doi.org\/10.1186\/s13059-020-02015-1.","DOI":"10.1186\/s13059-020-02015-1"},{"key":"2026041005053822025_j_jib-2024-0062_ref_047","doi-asserted-by":"crossref","unstructured":"Kanehisa, M, Furumichi, M, Sato, Y, Kawashima, M, Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res 2023;51:D587\u201392. https:\/\/doi.org\/10.1093\/nar\/gkac963.","DOI":"10.1093\/nar\/gkac963"},{"key":"2026041005053822025_j_jib-2024-0062_ref_048","doi-asserted-by":"crossref","unstructured":"Heinken, A, Hertel, J, Acharya, G, Ravcheev, DA, Nyga, M, Okpala, OE, et al.. Genome-scale metabolic reconstruction of 7,302 human microorganisms for personalized medicine. Nat Biotechnol 2023;41:1320\u201331. https:\/\/doi.org\/10.1038\/s41587-022-01628-0.","DOI":"10.1038\/s41587-022-01628-0"},{"key":"2026041005053822025_j_jib-2024-0062_ref_049","doi-asserted-by":"crossref","unstructured":"Vanunu, O, Magger, O, Ruppin, E, Shlomi, T, Sharan, R. Associating genes and protein complexes with disease via network propagation. PLoS Comput Biol 2010;6:1000641\u20137. https:\/\/doi.org\/10.1371\/journal.pcbi.1000641.","DOI":"10.1371\/journal.pcbi.1000641"},{"key":"2026041005053822025_j_jib-2024-0062_ref_050","doi-asserted-by":"crossref","unstructured":"Santolini, M, Barab\u00e1si, A-L. Predicting perturbation patterns from the topology of biological networks. Proc Natl Acad Sci 2018;115:6375\u201385. https:\/\/doi.org\/10.1073\/pnas.1720589115.","DOI":"10.1073\/pnas.1720589115"},{"key":"2026041005053822025_j_jib-2024-0062_ref_051","doi-asserted-by":"crossref","unstructured":"McLean, C, Sorokin, A, Simpson, TI, Douglas Armstrong, J, Sorokina, O. BioNAR: an integrated biological network analysis package in Bioconductor. Bioinformat Adv 2023;3:137\u20138. https:\/\/doi.org\/10.1093\/bioadv\/vbad137.","DOI":"10.1093\/bioadv\/vbad137"},{"key":"2026041005053822025_j_jib-2024-0062_ref_052","doi-asserted-by":"crossref","unstructured":"Marino, S, Hogue, IB, Ray, CJ, Kirschner, DE. A methodology for performing global uncertainty and sensitivity analysis in systems biology. J Theor Biol 2008;254:178\u201396. https:\/\/doi.org\/10.1016\/j.jtbi.2008.04.011.","DOI":"10.1016\/j.jtbi.2008.04.011"},{"key":"2026041005053822025_j_jib-2024-0062_ref_053","doi-asserted-by":"crossref","unstructured":"Maes, M, Schotte, C, Scharp\u00e9, S, Martin, M, Blockx, P. The effects of glucocorticoids on the availability of L-tryptophan and tyrosine in the plasma of depressed patients. J Affect Disord 1990;18:121\u20137. https:\/\/doi.org\/10.1016\/0165-0327(90)90068-j.","DOI":"10.1016\/0165-0327(90)90068-J"},{"key":"2026041005053822025_j_jib-2024-0062_ref_054","unstructured":"Badawy, AA. Tryptophan metabolism, disposition and utilization in pregnancy. Biosci Rep 2017;37."},{"key":"2026041005053822025_j_jib-2024-0062_ref_055","doi-asserted-by":"crossref","unstructured":"Calder, PC. Omega-3 fatty acids and inflammatory processes: from molecules to man. Biochem Soc Trans 2020;45:1105\u201315. https:\/\/doi.org\/10.1042\/bst20160474.","DOI":"10.1042\/BST20160474"},{"key":"2026041005053822025_j_jib-2024-0062_ref_056","unstructured":"Koca, I, Ucar, M, Arik, HO, Yilmaz, M, Dokuyucu, R. Alpha-lipoic acid could be a promising treatment in steroid-induced osteonecrosis. Eur Rev Med Pharmacol Sci 2022;26:7404\u201312. https:\/\/doi.org\/10.26355\/eurrev_202210_30009."},{"key":"2026041005053822025_j_jib-2024-0062_ref_057","doi-asserted-by":"crossref","unstructured":"Hers, HG. The control of glycogen metabolism in the liver. Annu Rev Biochem 1976;45:167\u201389. https:\/\/doi.org\/10.1146\/annurev.bi.45.070176.001123.","DOI":"10.1146\/annurev.bi.45.070176.001123"},{"key":"2026041005053822025_j_jib-2024-0062_ref_058","doi-asserted-by":"crossref","unstructured":"Van Raalte, DH, Ouwens, DM, Diamant, M. Novel insights into glucocorticoid-mediated diabetogenic effects: towards expansion of therapeutic options? Eur J Clin Invest 2009;39:81\u201393. https:\/\/doi.org\/10.1111\/j.1365-2362.2008.02067.x.","DOI":"10.1111\/j.1365-2362.2008.02067.x"},{"key":"2026041005053822025_j_jib-2024-0062_ref_059","unstructured":"Horiba, M. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 2016;310:E631\u201341."},{"key":"2026041005053822025_j_jib-2024-0062_ref_060","doi-asserted-by":"crossref","unstructured":"Silveira, JS. Glucagon reduces airway hyperreactivity, inflammation, and remodeling induced by ovalbumin. Sci Rep 2019;9:2695.","DOI":"10.1038\/s41598-019-42981-6"},{"key":"2026041005053822025_j_jib-2024-0062_ref_061","unstructured":"Sewell, AC. Lysine metabolism in mammalian brain: an update on the importance of recent discoveries. Amino Acids 1993;5:173\u201389."},{"key":"2026041005053822025_j_jib-2024-0062_ref_062","doi-asserted-by":"crossref","unstructured":"Hallen, A, Jamie, JF, Cooper, AJ. Lysine metabolism in mammalian brain: an update on the importance of recent discoveries. Biochim Biophys Acta Proteins Proteom 2013;1834:1802\u201312.","DOI":"10.1007\/s00726-013-1590-1"},{"key":"2026041005053822025_j_jib-2024-0062_ref_063","unstructured":"Struys, EA. Saccharopine dehydrogenase deficiency: a rare cause of hyperlysinemia and lysine-\u03b1-ketoglutarate reductase\/saccharopine dehydrogenase deficiency. Mol Genet Metabol 2013;109:107\u201311."},{"key":"2026041005053822025_j_jib-2024-0062_ref_064","unstructured":"Wagener, FA. The heme-thiolate structure of human cystathionine \u03b2-synthase and its small molecule chemistry: implications for hyperhomocysteinemia and atherosclerosis. Inorg Chem 2016;55:7586\u201393."},{"key":"2026041005053822025_j_jib-2024-0062_ref_065","doi-asserted-by":"crossref","unstructured":"Patterson, E, Wall, R, Fitzgerald, GF, Ross, RP, Stanton, C. Health implications of high dietary omega-6 polyunsaturated Fatty acids. J Nutr Metabol 2016;2012. https:\/\/doi.org\/10.1155\/2012\/539426.","DOI":"10.1155\/2012\/539426"},{"key":"2026041005053822025_j_jib-2024-0062_ref_066","doi-asserted-by":"crossref","unstructured":"Turnbaugh, PJ, Ley, RE, Hamady, M, Fraser-Liggett, CM, Knight, R, Gordon, JI. The human microbiome project. Nature 2007;449:804\u201310. https:\/\/doi.org\/10.1038\/nature06244.","DOI":"10.1038\/nature06244"},{"key":"2026041005053822025_j_jib-2024-0062_ref_067","doi-asserted-by":"crossref","unstructured":"Jin, Y. The role of the gut microbiome in systemic inflammatory disease. BMJ 2019;360:j5145.","DOI":"10.1136\/bmj.j5145"},{"key":"2026041005053822025_j_jib-2024-0062_ref_068","doi-asserted-by":"crossref","unstructured":"Han, MK, Huang, YJ, LiPuma, JJ, Boushey, HA, Boucher, RC, Cookson, WO, et al.. Significance of the microbiome in obstructive lung disease. Thorax 2016;67:456\u201363. https:\/\/doi.org\/10.1136\/thoraxjnl-2011-201183.","DOI":"10.1136\/thoraxjnl-2011-201183"},{"key":"2026041005053822025_j_jib-2024-0062_ref_069","doi-asserted-by":"crossref","unstructured":"Clarke, SF, Murphy, EF, Nilaweera, K, Ross, PR, Shanahan, F, O\u2019Toole, PW, et al.. The gut microbiota and its relationship to diet and obesity. Gut Microbes 2014;3:186\u2013202. https:\/\/doi.org\/10.4161\/gmic.20168.","DOI":"10.4161\/gmic.20168"},{"key":"2026041005053822025_j_jib-2024-0062_ref_070","doi-asserted-by":"crossref","unstructured":"Nicholson, JK, Holmes, E, Kinross, J, Burcelin, R, Gibson, G, Jia, W, et al.. Host-gut microbiota metabolic interactions. Science 2012;336:1262\u20137. https:\/\/doi.org\/10.1126\/science.1223813.","DOI":"10.1126\/science.1223813"},{"key":"2026041005053822025_j_jib-2024-0062_ref_071","unstructured":"Holmes, E. Metabolomics and models of human diseases. Nat Rev Genet 2018;13:285\u201396."},{"key":"2026041005053822025_j_jib-2024-0062_ref_072","doi-asserted-by":"crossref","unstructured":"Lynch, SV, Pedersen, O. The human intestinal microbiome in health and disease. N Engl J Med 2016;375:2369\u201379. https:\/\/doi.org\/10.1056\/nejmra1600266.","DOI":"10.1056\/NEJMra1600266"},{"key":"2026041005053822025_j_jib-2024-0062_ref_073","doi-asserted-by":"crossref","unstructured":"Quince, C. The impact of dietary fibre on gut microbiota in host health and disease. Cell Host Microbe 2017;21:705\u201315.","DOI":"10.1016\/j.chom.2018.05.012"},{"key":"2026041005053822025_j_jib-2024-0062_ref_074","doi-asserted-by":"crossref","unstructured":"Zitvogel, L, Ma, Y, Raoult, D, Kroemer, G, Gajewski, TF. The microbiome in cancer immunotherapy: diagnostic tools and therapeutic strategies. Science 2016;359:1366\u201370. https:\/\/doi.org\/10.1126\/science.aar6918.","DOI":"10.1126\/science.aar6918"}],"container-title":["Journal of Integrative Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jib-2024-0062\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jib-2024-0062\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:06:08Z","timestamp":1775797568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/jib-2024-0062\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":74,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,6,24]]},"published-print":{"date-parts":[[2026,4,7]]}},"alternative-id":["10.1515\/jib-2024-0062"],"URL":"https:\/\/doi.org\/10.1515\/jib-2024-0062","relation":{},"ISSN":["1613-4516"],"issn-type":[{"value":"1613-4516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]},"article-number":"20240062"}}