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A Comprehensive Metagenome Study Identifies Distinct Biological Pathways in Asthma Patients: An In-Silico Approach

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Abstract

Asthma is a multifactorial disease with phenotypes and several clinical and pathophysiological characteristics. Besides innate and adaptive immune responses, the gut microbiome generates Treg cells, mediating the allergic response to environmental factors and exposure to allergens. Because of the complexity of asthma, microbiome analysis and other precision medicine methods are now widely regarded as essential elements of efficient disease therapy. An in-silico pipeline enables the comparative taxonomic profiling of 16S rRNA metagenomic profiles of 20 asthmatic patients and 15 healthy controls utilizing QIIME2. Further, PICRUSt supports downstream gene enrichment and pathway analysis, inferring the enriched pathways in a diseased state. A significant abundance of the phylum Proteobacteria, Sutterella, and Megamonas is identified in asthma patients and a diminished genus Akkermansia. Nasal samples reveal a high relative abundance of Mycoplasma in the nasal samples. Further, differential functional profiling identifies the metabolic pathways related to cofactors and amino acids, secondary metabolism, and signaling pathways. These findings support that a combination of bacterial communities is involved in mediating the responses involved in chronic respiratory conditions like asthma by exerting their influence on various metabolic pathways.

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References

  • Al-Asmakh M, Hedin L (2015) Microbiota and the control of blood-tissue barriers. Tissue Barriers 3(3):e1039691

    Article  PubMed  PubMed Central  Google Scholar 

  • Andrews S, Krueger F, Segonds-Pichon A, Biggins L, Krueger C, Wingett S (2010) FastQC: a quality control tool for high throughput sequence data 370

  • Arrieta MC, Sadarangani M, Brown EM, Russell SL, Nimmo M, Dean J, Turvey SE, Chan ES, Finlay BB (2016) A humanized microbiota mouse model of ovalbumin-induced lung inflammation. Gut Microb 7:342–352

    Article  CAS  Google Scholar 

  • Arrieta MC, Arévalo A, Stiemsma L et al (2017) Associations between infant fungal and bacterial dysbiosis and childhood atopic wheeze in a nonindustrialized setting. J Allergy Clin Immunol 142(2):424–434

    Article  PubMed  Google Scholar 

  • Aßhauer KP, Wemheuer B, Daniel R, Meinicke P (2015) Tax4Fun: predicting functional profiles from metagenomic 16S rRNA data. Bioinformatics 31(17):2882–2884

    Article  PubMed  PubMed Central  Google Scholar 

  • Barbagallo M, Veronese N, Dominguez LJ (2021) Magnesium in aging, health and diseases. Nutrients 13(2):463

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barcik W, Boutin RC, Sokolowska M, Finlay BB (2020) The role of lung and gut microbiota in the pathology of asthma. Immunity 52(2):241–255

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Beiko RG, Hsiao W, Parkinson J (1849) 16S rRNA gene analysis with QIIME2: methods and protocols. Methods Mol Biol 1849:113–129

    Google Scholar 

  • Benson MJ, Pino-Lagos K, Rosemblatt M, Noelle RJ (2007) All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med 204(8):1765–1774

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Berg G, Rybakova D, Fischer D, Cernava T, Vergès MC, Charles T et al (2020) Correction to: microbiome definition re-visited: old concepts and new challenges. Microbiome 8(1):119

    Article  PubMed  PubMed Central  Google Scholar 

  • Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30(15):2114–2120

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA et al (2019) Reproducible, interactive, scalable, and extensible microbiome data science using QIIME 2. Nat Biotechnol 37(8):852–857

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Buchon N, Broderick NA, Poidevin M, Pradervand S, Lemaitre B (2009) Drosophila intestinal response to bacterial infection: activation of host defense and stem cell proliferation. Cell Host Microbe 5(2):200–211

    Article  PubMed  CAS  Google Scholar 

  • Budden KF, Shukla SD, Rehman SF, Bowerman KL, Keely S, Hugenholtz P et al (2019) Functional effects of the microbiota in chronic respiratory disease. Lancet Respir Med 7(10):907–920

    Article  PubMed  Google Scholar 

  • Burgin J, Ahamed A, Cummins C, Devraj R, Gueye K, Gupta D et al (2023) The European nucleotide archive in 2022. Nucleic Acids Res 51(D1):D121–D125

    Article  PubMed  CAS  Google Scholar 

  • Chakravorty S, Helb D, Burday M, Connell N, Alland D (2007) A detailed analysis of 16S ribosomal RNA gene segments for the diagnosis of pathogenic bacteria. J Microbiol Methods 69(2):330–339

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen G, Chen D, Feng Y, Wu W, Gao J, Chang C et al (2022a) Identification of key signaling pathways and genes in eosinophilic asthma and neutrophilic asthma by weighted gene co-expression network analysis. Front Mol Biosci 9:44

    Google Scholar 

  • Chen F, Gao W, Yu C, Li J, Yu F, Xia M, Liang J, Shi J, Lai Y (2022b) Age-associated changes of nasal bacterial microbiome in patients with chronic rhinosinusitis. Front Cell Infect Microbiol 12:786481

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, Huber T, Dalevi D, Hu P, Andersen GL (2006) Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol 72(7):5069–5072

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dominguez-Bello MG, Costello EK, Contreras M, Magris M, Hidalgo G, Fierer N, Knight R (2010) Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad Sci USA 107:11971–11975

    Article  PubMed  PubMed Central  Google Scholar 

  • Douglas GM, Maffei VJ, Zaneveld JR, Yurgel SN, Brown JR, Taylor CM, Huttenhower C, Langille MGI (2020) PICRUSt2 for prediction of metagenome functions. Nat Biotechnol 38(6):685–688

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ellwood P, Asher I, Billo N et al (2017) The Global Asthma Network rationale and methods for phase I global surveillance: prevalence, severity, management, and risk factors. Eur Resp J 49:1601605

    Article  Google Scholar 

  • Fahy JV (2015) Type 2 inflammation in asthma—present in most, absent in many. Nat Rev Immunol 15(1):57–65

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Farmanzadeh A, Qujeq D, Yousefi T (2022) The interaction network of MicroRNAs with cytokines and signaling pathways in allergic asthma. MicroRNA 11(2):104–117

    Article  PubMed  CAS  Google Scholar 

  • Farshchi MK, Azad FJ, Salari R, Mirsadraee M, Anushiravani M (2017) A viewpoint on the leaky gut syndrome to treat allergic asthma: a novel opinion. J Evid Based Complement Altern Med 22(3):378–380

    Article  Google Scholar 

  • Fazlollahi M, Lee TD, Andrade J, Oguntuyo K, Chun Y, Grishina G et al (2018) The nasal microbiome in asthma. J Allergy Clin Immunol 142(3):834–843

    Article  PubMed  PubMed Central  Google Scholar 

  • Fogarty A, Broadfield E, Lewis S, Lawson N, Britton J (2004) Amino acids and asthma: a case-control study. Eur Respir J 23(4):565–568

    Article  PubMed  CAS  Google Scholar 

  • Frati F, Salvatori C, Incorvaia C, Bellucci A, Di Cara G, Marcucci F, Esposito S (2018) The role of the microbiome in asthma: the gut-lung axis. Int J Mol Sci 20(1):123

    Article  PubMed  PubMed Central  Google Scholar 

  • Fujimura KE, Lynch SV (2015) Microbiota in allergy and asthma and the emerging relationship with the gut microbiome. Cell Host Microbe 17(5):592–602

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Golebski K, Layhadi JA, Sahiner U, Steveling-Klein EH, Lenormand MM, Li RC et al (2021) Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response. Immunity 54(2):291–307

    Article  PubMed  CAS  Google Scholar 

  • Hammad H, Lambrecht BN (2021) The basic immunology of asthma. Cell 184(6):1469–1485

    Article  PubMed  CAS  Google Scholar 

  • Han YY, Blatter J, Brehm JM, Forno E, Litonjua AA, Celedón JC (2013) Diet and asthma: vitamins and methyl donors. Lancet Respir Med 1(10):813–822

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jatzlauk G, Bartel S, Heine H, Schloter M, Krauss-Etschmann S (2017) Environmental bacteria and their metabolites influence allergies, asthma, and host microbiota. Allergy 72(12):1859–1867

    Article  PubMed  CAS  Google Scholar 

  • Kamada N, Núñez G (2013) Role of the gut microbiota in the development and function of lymphoid cells. J Immunol 190(4):1389–1395

    Article  PubMed  CAS  Google Scholar 

  • Kim YS, Han D, Mo JH, Kim YM, Kim DW, Choi HG et al (2021) Antibiotic-dependent relationships between the nasal microbiome and secreted proteome in nasal polyps. Allergy Asthma Immunol Res 13(4):589

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Konopiński MK (2020) Shannon diversity index: a call to replace the original Shannon’s formula with unbiased estimator in the population genetics studies. PeerJ 8:e9391

    Article  PubMed  PubMed Central  Google Scholar 

  • Larsen JM (2017) The immune response to Prevotella bacteria in chronic inflammatory disease. Immunology 151(4):363–374

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee YC, Lee CT, Lai YR, Chen VC, Stewart R (2016) Association of asthma and anxiety: a nationwide population based study in Taiwan. J Affect Disord 189:98–105

    Article  PubMed  Google Scholar 

  • Liu X, Wang Y, Chen C, Liu K (2021) Mycoplasma pneumoniae infection and risk of childhood asthma: a systematic review and meta-analysis. Microb Pathog 155:104893

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Nagy P, Bonfini A, Houtz P, Bing XL, Yang X, Buchon N (2022) Microbes affect gut epithelial cell composition through immune-dependent regulation of intestinal stem cell differentiation. Cell Rep 38(13):110572

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ly NP, Litonjua A, Gold DR, Celedón JC (2011) Gut microbiota, probiotics, and vitamin D: interrelated exposures influencing allergy, asthma, and obesity? J Allergy Clin Immunol 127(5):1087–1094

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Michalovich D, Rodriguez-Perez N, Smolinska S, Pirozynski M, Mayhew D, Uddin S et al (2019) Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients. Nat Commun 10(1):1–14

    Article  Google Scholar 

  • Mims JW (2015) Asthma: definitions and pathophysiology. Int Forum Allergy Rhinol 5(S1):S2–S6

    Article  PubMed  Google Scholar 

  • Omenetti S, Bussi C, Metidji A, Iseppon A, Lee S, Tolaini M et al (2019) The intestine harbors functionally distinct homeostatic tissue-resident and inflammatory Th17 cells. Immunity 51(1):77–89

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oulas A, Pavloudi C, Polymenakou P, Pavlopoulos GA, Papanikolaou N, Kotoulas G et al (2015) Metagenomics: tools and insights for analyzing next-generation sequencing data derived from biodiversity studies. Bioinform Biol Insights 9:75–88

    Article  PubMed  PubMed Central  Google Scholar 

  • Pascal M, Perez-Gordo M, Caballero T, Escribese MM, Lopez Longo MN, Luengo O et al (2018) Microbiome and allergic diseases. Front Immunol. https://doi.org/10.3389/fimmu.2018.01584

    Article  PubMed  PubMed Central  Google Scholar 

  • Penders J, Stobberingh EE, van den Brandt PA, Thijs C (2007) The role of the intestinal microbiota in the development of atopic disorders. Allergy 62:1223–1236

    Article  PubMed  CAS  Google Scholar 

  • Pérez-Cobas AE, Gomez-Valero L, Buchrieser C (2020) Metagenomic approaches in microbial ecology: an update on whole-genome and marker gene sequencing analyses. Microb Genomics. https://doi.org/10.1099/mgen.0.000409

    Article  Google Scholar 

  • Pernis AB, Rothman PB (2002) JAK-STAT signaling in asthma. J Clin Investig 109(10):1279–1283

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pfeffer PE, Lu H, Mann EH, Chen YH, Ho TR, Cousins DJ et al (2018) Effects of vitamin D on inflammatory and oxidative stress responses of human bronchial epithelial cells exposed to particulate matter. PLoS ONE 13(8):e0200040

    Article  PubMed  PubMed Central  Google Scholar 

  • Rutayisire E, Huang K, Liu Y, Tao F (2016) The mode of delivery affects the diversity and colonization pattern of the gut microbiota during the first year of infants’s life: a systematic review. BMC Gastroenterol 16:86

    Article  PubMed  PubMed Central  Google Scholar 

  • Salameh M et al (2020) The role of gut microbiota in atopic asthma and allergy, implications in the understanding of disease pathogenesis. Scand J Immunol 91(3):e12855

    Article  PubMed  Google Scholar 

  • Steinmeyer S, Lee K, Jayaraman A, Alaniz RC (2015) Microbiota metabolite regulation of host immune homeostasis: a mechanistic missing link. Curr Allergy Asthma Rep 15(5):24

    Article  PubMed  CAS  Google Scholar 

  • Suzuki M, Suzuki T, Watanabe M, Hatakeyama S, Kimura S, Nakazono A et al (2021) Role of intracellular zinc in molecular and cellular function in allergic inflammatory diseases. Allergol Int 70(2):190–200

    Article  PubMed  CAS  Google Scholar 

  • Ver Heul A, Planer J, Kau AL (2019) The human microbiota and asthma. Clin Rev Allergy Immunol 57(3):350–363

    Article  PubMed  Google Scholar 

  • Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M et al (2020) Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. The Lancet 396(10258):1204–1222

    Article  Google Scholar 

  • Walters KE, Martiny JB (2020) Alpha-, beta-, and gamma-diversity of bacteria varies across habitats. PLoS ONE 15(9):e0233872

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang Q, Li F, Liang B, Liang Y, Chen S, Mo X et al (2018) A metagenome-wide association study of gut microbiota in asthma in UK adults. BMC Microbiol 18(1):1–7

    Article  Google Scholar 

  • Watson RL, de Koff EM, Bogaert D (2018) Characterizing the respiratory microbiome. Eur Respir J 53(2):1801711

    Article  Google Scholar 

  • Yeh JJ, Wang YC, Hsu WH, Kao CH (2016) Incident asthma and Mycoplasma pneumoniae: a nationwide cohort study. J Allergy Clin Immunol 137(4):1017–1023

    Article  PubMed  Google Scholar 

  • Yin SS, Ma FL, Gao X (2017) Association of Mycoplasma pneumoniae infection with increased risk of asthma in children. Exp Ther Med 13(5):1813–1819

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Q, Cox M, Liang Z, Brinkmann F, Cardenas PA, Duff R et al (2016) Airway microbiota in severe asthma and relationship to asthma severity and phenotypes. PLoS ONE 11(4):e0152724

    Article  PubMed  PubMed Central  Google Scholar 

  • Zheng D, Liwinski T, Elinav E (2020) Interaction between microbiota and immunity in health and disease. Cell Res 30(6):492–506

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

SR is grateful to DBT for providing the fellowship. PS acknowledges UGC for providing the fellowship. P. Somvanshi is grateful to SC&IS, SCSM, Jawaharlal Nehru University. The authors thank Jawaharlal Nehru University, the Department of Biotechnology, and the University Grants Commission for the facility and fellowship for the requisite support.

Funding

This study was supported by BIC DBT and UGC.

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Authors and Affiliations

  1. School of Computational & Integrative Sciences (SC&IS), Jawaharlal Nehru University, JNU Campus, New Delhi, 110067, India

    Samiksha Rana, Pooja Singh & Pallavi Somvanshi

  2. Special Centre of Systems Medicine (SCSM), Jawaharlal Nehru University, JNU Campus, New Delhi, 110067, India

    Pallavi Somvanshi

  3. Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, T6G 2P5, Canada

    Tulika Bhardwaj

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  1. Samiksha Rana
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  2. Pooja Singh
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  3. Tulika Bhardwaj
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  4. Pallavi Somvanshi
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Contributions

SR acquired data, analysis, and interpretation of data and manuscript drafting. PS (Pooja Singh) performed study concepts and design, data acquisition, analysis, and interpretation of data. PS (Pallavi Somvanshi) and TB did the data interpretation and manuscript drafting. All the authors reviewed and approved the manuscript.

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Correspondence to Pallavi Somvanshi.

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Rana, S., Singh, P., Bhardwaj, T. et al. A Comprehensive Metagenome Study Identifies Distinct Biological Pathways in Asthma Patients: An In-Silico Approach. Biochem Genet (2024). https://doi.org/10.1007/s10528-023-10635-y

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