Microbial genes outperform species and SNVs as diagnostic markers for Crohn’s disease on multicohort fecal metagenomes empowered by artificial intelligence

References

• Ng SC, Shi HY, Hamidi N, Underwood FE, Tang W, Benchimol EI, Panaccione R, Ghosh S, Wu JCY, Chan FKL, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390(10114):2769–18. doi:10.1016/S0140-6736(17)32448-0.
   PubMed Web of Science ®Google Scholar
• Alatab S, Sepanlou SG, Ikuta K, Vahedi H, Bisignano C, Safiri S, Sadeghi A, Nixon MR, Abdoli A, Abolhassani H. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5(1):17–30. doi:10.1016/S2468-1253(19)30333-4.
   PubMed Web of Science ®Google Scholar
• Feuerstein JD, Cheifetz AS. Crohn disease: epidemiology, diagnosis, and management. Mayo Clin Proc. 2017;92(7):1088–1103. doi:10.1016/j.mayocp.2017.04.010.
   PubMed Web of Science ®Google Scholar
• Maaser C, Sturm A, Vavricka SR, Kucharzik T, Fiorino G, Annese V, Calabrese E, Baumgart DC, Bettenworth D, Borralho Nunes P, et al. ECCO-ESGAR guideline for diagnostic assessment in IBD Part 1: initial diagnosis, monitoring of known IBD, detection of complications. J Crohns Colitis. 2019;13(2):144–164. doi:10.1093/ecco-jcc/jjy113.
   PubMed Web of Science ®Google Scholar
• Feld LD, Kirk K, Feld AD. A high quality approach to addressing complications of endoscopy and optimizing risk management strategies. Tech Innovations In Gastrointestinal Endoscopy. 2022;24(4):390–395. doi:10.1016/j.tige.2022.03.006.
   Google Scholar
• Lewis JD. The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. Gastroenterology. 2011;140(6):1817–1826.e2. doi:10.1053/j.gastro.2010.11.058.
   PubMed Web of Science ®Google Scholar
• Mosli MH, Zou G, Garg SK, Feagan SG, MacDonald JK, Chande N, Sandborn WJ, Feagan BG. C-Reactive protein, fecal calprotectin, and stool lactoferrin for detection of endoscopic activity in symptomatic inflammatory bowel disease patients: a systematic review and meta-analysis. American Journal Of Gastroenterology. 2015;110:802–819. quiz 20. doi:10.1038/ajg.2015.120.
   PubMed Web of Science ®Google Scholar
• Dubinsky M, Braun J. Diagnostic and prognostic microbial biomarkers in inflammatory bowel diseases. Gastroenterology. 2015;149(5):1265–74.e3. doi:10.1053/j.gastro.2015.08.006.
   PubMed Web of Science ®Google Scholar
• Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Avila-Pacheco J, Poon TW, Andrews E, Ajami NJ, Bonham KS, Brislawn CJ, et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature. 2019;569(7758):655–662. doi:10.1038/s41586-019-1237-9.
   PubMed Web of Science ®Google Scholar
• Huang Q, Zhang X, Hu Z. Application of artificial intelligence modeling technology based on multi-omics in noninvasive diagnosis of inflammatory bowel disease. J Inflamm Res. 2021;14:1933–1943. doi:10.2147/JIR.S306816.
   PubMed Web of Science ®Google Scholar
• Pascal V, Pozuelo M, Borruel N, Casellas F, Campos D, Santiago A, et al. A microbial signature for Crohn’s disease. Gut. 2017;66:813–822. doi:10.1136/gutjnl-2016-313235.
   PubMed Web of Science ®Google Scholar
• Franzosa EA, Sirota-Madi A, Avila-Pacheco J, Fornelos N, Haiser HJ, Reinker S, Vatanen T, Hall AB, Mallick H, McIver LJ, et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat Microbiol. 2019;4(2):293–305. doi:10.1038/s41564-018-0306-4.
   PubMed Web of Science ®Google Scholar
• Tierney BT, Tan Y, Kostic AD, Patel CJ. Gene-level metagenomic architectures across diseases yield high-resolution microbiome diagnostic indicators. Nat Commun. 2021;12(1):2907. doi:10.1038/s41467-021-23029-8.
   PubMed Web of Science ®Google Scholar
• Liu NN, Jiao N, Tan JC, Wang Z, Wu D, Wang AJ, Chen J, Tao L, Zhou C, Fang W, et al. Multi-kingdom microbiota analyses identify bacterial–fungal interactions and biomarkers of colorectal cancer across cohorts. Nat Microbiol. 2022;7(2):238–250. doi:10.1038/s41564-021-01030-7.
   PubMed Web of Science ®Google Scholar
• Yan Y, Nguyen LH, Franzosa EA, Huttenhower C. Strain-level epidemiology of microbial communities and the human microbiome. Genome Med. 2020;12(1):71. doi:10.1186/s13073-020-00765-y.
   PubMed Web of Science ®Google Scholar
• Ma C, Chen K, Wang Y, Cen C, Zhai Q, Zhang J. Establishing a novel colorectal cancer predictive model based on unique gut microbial single nucleotide variant markers. Gut Microbes. 2021;13(1):1–6. doi:10.1080/19490976.2020.1869505.
   Web of Science ®Google Scholar
• Jiang S, Chen D, Ma C, Liu H, Huang S, Zhang J. Establishing a novel inflammatory bowel disease prediction model based on gene markers identified from single nucleotide variants of the intestinal microbiota. iMeta. 2022;1(3):1. doi:10.1002/imt2.40.
   Google Scholar
• Gao W, Chen W, Yin W, Zhu X, Gao S, Liu L, Wu D, Zhu R, Jiao N. Identification and validation of microbial biomarkers from cross-cohort datasets using xMarkerfinder. Protocol Exchange. 2022.
   Google Scholar
• Coker OO, Liu C, Wu WKK, Wong SH, Jia W, Sung JJY, Yu J. Altered gut metabolites and microbiota interactions are implicated in colorectal carcinogenesis and can be non-invasive diagnostic biomarkers. Microbiome. 2022;10(1):35. doi:10.1186/s40168-021-01208-5.
   PubMed Web of Science ®Google Scholar
• Hallen-Adams HE, Suhr MJ. Fungi in the healthy human gastrointestinal tract. Virulence. 2017;8(3):352–358. doi:10.1080/21505594.2016.1247140.
   PubMed Web of Science ®Google Scholar
• Rashid T, Ebringer A, Wilson C. The role of Klebsiella in Crohn’s disease with a potential for the use of antimicrobial measures. Int J Rheumatol. 2013;2013:610393. doi:10.1155/2013/610393.
   PubMedGoogle Scholar
• Schirmer M, Garner A, Vlamakis H, Xavier RJ. Microbial genes and pathways in inflammatory bowel disease. Nat Rev Microbiol. 2019;17(8):497–511. doi:10.1038/s41579-019-0213-6.
   PubMed Web of Science ®Google Scholar
• Lengeler JW, Jahreis K. Bacterial PEP-dependent carbohydrate: phosphotransferase systems couple sensing and global control mechanisms. Contrib Microbiol. 2009;16:65–87.
   PubMedGoogle Scholar
• Västermark A, Saier MH Jr. The involvement of transport proteins in transcriptional and metabolic regulation. Curr Opin Microbiol. 2014;18:8–15. doi:10.1016/j.mib.2014.01.002.
   PubMed Web of Science ®Google Scholar
• Saier MH Jr. The bacterial phosphotransferase system: new frontiers 50 years after its discovery. J Mol Microbiol Biotechnol. 2015;25(2–3):73–78. doi:10.1159/000381215.
   PubMed Web of Science ®Google Scholar
• Han Y, Wang B, Gao H, He C, Hua R, Liang C, Xin S, Wang Y, Xu J. Insight into the relationship between Oral Microbiota and the Inflammatory Bowel Disease. Microorganisms. 2022;10(9):10. doi:10.3390/microorganisms10091868.
   Web of Science ®Google Scholar
• Abdelbary MMH, Hatting M, Bott A, Dahlhausen A, Keller D, Trautwein C, Conrads G. The oral-gut axis: salivary and fecal microbiome dysbiosis in patients with inflammatory bowel disease. Front Cell Infect Microbiol. 2022;12:1010853. doi:10.3389/fcimb.2022.1010853.
   PubMed Web of Science ®Google Scholar
• Hu S, Mok J, Gowans M, Ong DEH, Hartono JL, Lee JWJ. Oral Microbiome of Crohn’s disease patients with and without Oral Manifestations. J Crohns Colitis. 2022;16(10):1628–1636. doi:10.1093/ecco-jcc/jjac063.
   PubMed Web of Science ®Google Scholar
• Rojas-Tapias DF, Brown EM, Temple ER, Onyekaba MA, Mohamed AMT, Duncan K, Schirmer M, Walker RL, Mayassi T, Pierce KA, et al. Inflammation-associated nitrate facilitates ectopic colonization of oral bacterium Veillonella parvula in the intestine. Nat Microbiol. 2022;7(10):1673–1685. doi:10.1038/s41564-022-01224-7.
   PubMed Web of Science ®Google Scholar
• Wu M-C, Chen Y-C, Lin T-L, Hsieh P-F, Wang J-T, Camilli A, Camilli A. Cellobiose-specific phosphotransferase system of Klebsiella pneumoniae and its importance in biofilm formation and virulence. Infect Immun. 2012;80(7):2464–2472. doi:10.1128/IAI.06247-11.
   PubMed Web of Science ®Google Scholar
• Jeckelmann JM, Erni B. The mannose phosphotransferase system (Man-PTS) - Mannose transporter and receptor for bacteriocins and bacteriophages. Biochimica et Biophysica Acta (BBA) - Biomembr. 2020;1862(11):183412. doi:10.1016/j.bbamem.2020.183412.
   PubMed Web of Science ®Google Scholar
• Turnbaugh PJ, Ridaura VK, Faith JJ, Rey FE, Knight R, Gordon JI. The effect of diet on the human gut microbiome: a metagenomic analysis in humanized gnotobiotic mice. Sci Transl Med. 2009;1(6):6ra14. doi:10.1126/scitranslmed.3000322.
   PubMed Web of Science ®Google Scholar
• Zhao L, Zhang F, Ding X, Wu G, Lam YY, Wang X, Fu H, Xue X, Lu C, Ma J, et al. Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science. 2018;359(6380):1151–1156. doi:10.1126/science.aao5774.
   PubMed Web of Science ®Google Scholar
• Wu G, Zhao N, Zhang C, Lam YY, Zhao L. Guild-based analysis for understanding gut microbiome in human health and diseases. Genome Med. 2021;13(1):22. doi:10.1186/s13073-021-00840-y.
   PubMed Web of Science ®Google Scholar
• Guo Y, Kitamoto S, Kamada N. Microbial adaptation to the healthy and inflamed gut environments. Gut Microbes. 2020;12(1):1857505. doi:10.1080/19490976.2020.1857505.
   PubMed Web of Science ®Google Scholar
• Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157(1):121–141. doi:10.1016/j.cell.2014.03.011.
   PubMed Web of Science ®Google Scholar
• Hall AB, Yassour M, Sauk J, Garner A, Jiang X, Arthur T, Lagoudas GK, Vatanen T, Fornelos N, Wilson R, et al. A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med. 2017;9(1):103. doi:10.1186/s13073-017-0490-5.
   PubMedGoogle Scholar
• Lewis JD, Chen EZ, Baldassano RN, Otley AR, Griffiths AM, Lee D, Bittinger K, Bailey A, Friedman E, Hoffmann C, et al. Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn’s disease. Cell Host Microbe. 2015;18(4):489–500. doi:10.1016/j.chom.2015.09.008.
   PubMed Web of Science ®Google Scholar
• Schirmer M, Franzosa EA, Lloyd-Price J, McIver LJ, Schwager R, Poon TW, Ananthakrishnan AN, Andrews E, Barron G, Lake K, et al. Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat Microbiol. 2018;3(3):337–346. doi:10.1038/s41564-017-0089-z.
   PubMed Web of Science ®Google Scholar
• Nielsen HB, Almeida M, Juncker AS, Rasmussen S, Li J, Sunagawa S, Plichta DR, Gautier L, Pedersen AG, Le Chatelier E, et al. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat Biotechnol. 2014;32(8):822–828. doi:10.1038/nbt.2939.
   PubMed Web of Science ®Google Scholar
• Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Krogh Pedersen H, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262–266. doi:10.1038/nature15766.
   PubMed Web of Science ®Google Scholar
• Qin N, Yang F, Li A, Prifti E, Chen Y, Shao L, Guo J, Le Chatelier E, Yao J, Wu L, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014;513(7516):59–64. doi:10.1038/nature13568.
   PubMed Web of Science ®Google Scholar
• Bedarf JR, Hildebrand F, Coelho LP, Sunagawa S, Bahram M, Goeser F, Bork P, Wüllner U. Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson’s disease patients. Genome Med. 2017;9(1):39. doi:10.1186/s13073-017-0428-y.
   PubMedGoogle Scholar
• He Q, Gao Y, Jie Z, Yu X, Laursen JM, Xiao L, et al. Two distinct metacommunities characterize the gut microbiota in Crohn’s disease patients. Gigascience. 2017;6:1–11. doi:10.1093/gigascience/gix050.
   Web of Science ®Google Scholar
• Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017;45(D1):D353–D361. doi:10.1093/nar/gkw1092.
   PubMed Web of Science ®Google Scholar
• Chicco D, Jurman G. The advantages of the Matthews correlation coefficient (MCC) over F1 score and accuracy in binary classification evaluation. Bmc Genomics. 2020;21(1):6. doi:10.1186/s12864-019-6413-7.
   PubMed Web of Science ®Google Scholar
• Lundberg SM, Lee S-I. A unified approach to interpreting model predictions. NIPS’17: Proceedings of the 31st International Conference on Neural Information Processing Systems; Long Beach California USA. 2017. p. 4768–4777.
   Google Scholar
• Wu Y, Jiao N, Zhu R, Zhang Y, Wu D, Wang AJ, Fang S, Tao L, Li Y, Cheng S, et al. Identification of microbial markers across populations in early detection of colorectal cancer. Nat Commun. 2021;12(1):3063. doi:10.1038/s41467-021-23265-y.
   PubMed Web of Science ®Google Scholar
• Thomas AM, Manghi P, Asnicar F, Pasolli E, Armanini F, Zolfo M, Beghini F, Manara S, Karcher N, Pozzi C, et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat Med. 2019;25(4):667–678. doi:10.1038/s41591-019-0405-7.
   PubMed Web of Science ®Google Scholar
• Ma S, Shungin D, Mallick H, Schirmer M, Nguyen LH, Kolde R, Franzosa E, Vlamakis H, Xavier R, Huttenhower C, et al. Population structure discovery in meta-analyzed microbial communities and inflammatory bowel disease using MMUPHin. Genome Biol. 2022;23(1):208. doi:10.1186/s13059-022-02753-4.
   PubMed Web of Science ®Google Scholar