International Journal of Frontiers in Medicine, 2024, 6(11); doi: 10.25236/IJFM.2024.061107.
Meng Li1,2, Jinman Liu1, Guohua Liu1
1Jiangmen Wuyi Tranditional Chinese Medicine Hospital, Jiangmen, China
2Jinan University, Guangzhou, China
Pediatric asthma, a highly heterogeneous disorder, poses significant health risks to children and strains healthcare systems worldwide. While breastfeeding is recognized as a pivotal early-life factor, its impact on childhood asthma development remains contentious. Using a two-sample Mendelian randomization approach, we identify instrumental variables significantly associated with breastfeeding and assess their impact on pediatric asthma risk. Our results indicate a significant negative correlation between breastfeeding and childhood asthma, suggesting that breastfeeding acts as a protective factor. Sensitivity analysis confirms the robustness of our findings. Furthermore, we conduct differential gene expression analysis to elucidate the genetic mechanisms underlying asthma occurrence and its association with breastfeeding. Through reanalysis of existing genetic data and gene set enrichment analysis, we identify key genes and pathways implicated in asthma pathogenesis, shedding light on the potential molecular mechanisms underlying breastfeeding's protective effects. In conclusion, our study provides compelling evidence supporting breastfeeding as a crucial factor in mitigating pediatric asthma risk.
breastfeeding; pediatric asthma; Mendelian randomization analysis; Expression of differential genes
Meng Li, Jinman Liu, Guohua Liu. Breastfeeding can relieve asthma: A two-sample Mendelian analysis and genetic database mining. International Journal of Frontiers in Medicine (2024), Vol. 6, Issue 11: 42-52. https://doi.org/10.25236/IJFM.2024.061107.
[1] Hoch HE, Houin PR, Stillwell PC. Asthma in Children: A Brief Review for Primary Care Providers. Pediatr Ann 2019; 48(3):e103-e9.
[2] Oksel C, Haider S, Fontanella S, Frainay C, Custovic A. Classification of Pediatric Asthma: From Phenotype Discovery to Clinical Practice. Front Pediatr 2018;6:258
[3] Papadopoulos NG, Čustović A, Cabana MD, et al. Pediatric asthma: An unmet need for more effective, focused treatments. Pediatr Allergy Immunol 2019; 30: 7-16.
[4] M.Masoli, D. Fabian, S. Holt, R. Beasley, Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee report, Allergy. 59 (2004) 469–478.
[5] C. Flohr, J. Mann, New insights into the epidemiology of childhood atopic dermatitis, Allergy. 69 (2014) 3–16.
[6] I.A. Deckers, S. McLean, S. Linssen, M. Mommers, C.P. van Schayck, A. Sheikh,Investigating internatieview of epidemiological studies, PLoS One 7(2012) e39803.
[7] Ruan Q, Jiang Y, Shi Y. Maternal smoking around birth and its influence on offspring allergic diseases: A mendelian randomization study. World Allergy Organ J. 2024 Feb 4; 17(2):100875. doi: 10.1016/j.waojou.2024.100875. PMID: 38351904; PMCID: PMC10862070.
[8] Krenz-Niedbała M, Kościński K, Puch EA, Zelent A, Bręborowicz A. Is the Relationship Between Breastfeeding and Childhood Risk of Asthma and Obesity Mediated by Infant Antibiotic Treatment? Breastfeed Med. 2015 Jul-Aug; 10(6):326-33. doi: 10.1089/bfm.2014.0173. Epub 2015 Jun 25. PMID: 26110340.
[9] Sly PD, Holt PG. Breast is best for preventing asthma and allergies--or is it? Lancet. 2002 Sep 21; 360(9337):887-8. doi: 10.1016/S0140-6736(02)11068-3. PMID: 12354466.
[10] Hwang SH, Shin H, Stybayeva G, Kim DH. Perinatal Risk Factors in Relation to Asthma and Allergic Rhinitis in Children and Adolescents. Clin Exp Otorhinolaryngol. 2024 Apr 8. doi: 10.21053/ceo.2024.00024. Epub ahead of print. PMID: 38584131.
[11] Victora CG, Bahl R, Barros AJ, França GV, Horton S, Krasevec J, Murch S, Sankar MJ, Walker N, Rollins NC; Lancet Breastfeeding Series Group. Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect. Lancet. 2016 Jan 30; 387(10017):475-90. doi: 10.1016/S0140-6736(15) 01024-7. PMID: 26869575.
[12] Leung JY, Kwok MK, Leung GM, Schooling CM. Breastfeeding and childhood hospitalizations for asthma and other wheezing disorders. Ann Epidemiol. 2016 Jan; 26(1):21-7.e1-3. doi: 10.1016/j. annepidem. 2015.10.001. Epub 2015 Oct 23. PMID: 26559328.
[13] Obbagy JE, English LK, Wong YP, Butte NF, Dewey KG, Fleischer DM, Fox MK, Greer FR, Krebs NF, Scanlon KS, Stoody EE. Complementary feeding and food allergy, atopic dermatitis/eczema, asthma, and allergic rhinitis: a systematic review. Am J Clin Nutr. 2019 Mar 1; 109(Suppl_7):890S-934S. doi: 10.1093/ajcn/nqy220. PMID: 30982864.
[14] Wilson K, Gebretsadik T, Adgent MA, Loftus C, Karr C, Moore PE, Sathyanarayana S, Byington N, Barrett E, Bush N, Nguyen R, Hartman TJ, LeWinn KZ, Calvert A, Mason WA, Carroll KN. The association between duration of breastfeeding and childhood asthma outcomes. Ann Allergy Asthma Immunol. 2022 Aug; 129(2):205-211. doi: 10.1016/j.anai.2022.04.034. Epub 2022 May 10. PMID: 35552008; PMCID: PMC9442497.
[15] Kumar PH, Devgan A. The Association of Breastfeeding With Childhood Asthma: A Case-Control Study From India. Cureus. 2021 Nov 22;13(11):e19810. doi: 10.7759/cureus.19810. PMID: 34963832; PMCID: PMC8695657.
[16] Xue M, Dehaas E, Chaudhary N, O'Byrne P, Satia I, Kurmi OP. Breastfeeding and risk of childhood asthma: a systematic review and meta-analysis. ERJ Open Res. 2021 Dec 13; 7(4):00504-2021. doi: 10.1183/23120541.00504-2021. PMID: 34912884; PMCID: PMC8666625.
[17] Harvey SM, Murphy VE, Gibson PG, Collison A, Robinson P, Sly PD, Mattes J, Jensen ME. Maternal asthma, breastfeeding, and respiratory outcomes in the first year of life. Pediatr Pulmonol. 2020 Jul;55(7):1690-1696. doi: 10.1002/ppul.24756. Epub 2020 Apr 6. PMID: 32250063.
[18] Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: A review. Res Synth Methods. 2019 Dec; 10(4):486-496. doi: 10.1002/jrsm.1346. Epub 2019 Apr 23. PMID: 30861319; PMCID: PMC6973275.
[19] Christenson SA, Steiling K, van den Berge M, Hijazi K, Hiemstra PS, Postma DS, Lenburg ME, Spira A, Woodruff PG. Asthma-COPD overlap. Clinical relevance of genomic signatures of type 2 inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2015 Apr 1;191(7):758-66. doi: 10.1164/rccm.201408-1458OC. PMID: 25611785; PMCID: PMC4407484.
[20] Li X, Bechara R, Zhao J, McGeachy MJ, Gaffen SL. IL-17 receptor-based signaling and implications for disease. Nat Immunol. 2019 Dec;20(12):1594-1602. doi: 10.1038/s41590-019-0514-y. Epub 2019 Nov 19. PMID: 31745337; PMCID: PMC6943935.
[21] Kanarek P, Bogiel T, Breza-Boruta B. Legionellosis risk-an overview of Legionella spp. habitats in Europe. Environ Sci Pollut Res Int. 2022 Nov;29(51):76532-76542. doi: 10.1007/s11356-022-22950-9. Epub 2022 Sep 26. PMID: 36161570; PMCID: PMC9511453.
[22] Shi Z, He Z, Wang DW. CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators. Molecules. 2022 Jun 16;27(12):3873. doi: 10.3390/molecules27123873. PMID: 35744996; PMCID: PMC9230517.
[23] Iftode N, Rădulescu MA, Aramă ȘS, Aramă V. Update on Kaposi sarcoma-associated herpesvirus (KSHV or HHV8) - review. Rom J Intern Med. 2020 Dec 17;58(4):199-208. doi: 10.2478/rjim-2020-0017. PMID: 32681788.
[24] Zheng Q, Xu C, Jiang Z, Zhu M, Chen C, Fu F. Smart Actuators Based on External Stimulus Response. Front Chem. 2021 May 31;9:650358. doi: 10.3389/fchem.2021.650358. PMID: 34136462; PMCID: PMC8200850.
[25] Calebiro D, Koszegi Z, Lanoiselée Y, Miljus T, O'Brien S. G protein-coupled receptor-G protein interactions: a single-molecule perspective. Physiol Rev. 2021 Jul 1;101(3):857-906. doi: 10.1152/ physrev. 00021.2020. Epub 2020 Dec 17. PMID: 33331229.
[26] Metzler H, Grèzes J. Repeatedly adopting power postures does not affect hormonal correlates of dominance and affiliative behavior. PeerJ. 2019 Jun 17;7:e6726. doi: 10.7717/peerj.6726. PMID: 31245173; PMCID: PMC6585898.
[27] Yılmaz D, Culha M. Discrimination of Receptor-Mediated Endocytosis by Surface-Enhanced Raman Scattering. Langmuir. 2022 May 24;38(20):6281-6294. doi: 10.1021/acs.langmuir.1c03305. Epub 2022 May 13. PMID: 35549265; PMCID: PMC9134499.
[28] Skálová A, Hyrcza MD, Leivo I. Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Salivary Glands. Head Neck Pathol. 2022 Mar;16(1):40-53. doi: 10.1007/s12105-022-01420-1. Epub 2022 Mar 21. PMID: 35312980; PMCID: PMC9018948.
[29] Feiteng C, Lei C, Deng L, Chaoliang X, Zijie X, Yi S, Minglei S. Relaxin inhibits renal fibrosis and the epithelial-to-mesenchymal transition via the Wnt/β-catenin signaling pathway. Ren Fail. 2022 Dec; 44(1): 513-524. doi: 10.1080/0886022X.2022.2044351. PMID: 35311469; PMCID: PMC8942541.
[30] Degirmenci U, Wang M, Hu J. Targeting Aberrant RAS/RAF/MEK/ERK Signaling for Cancer Therapy. Cells. 2020 Jan 13;9(1):198. doi: 10.3390/cells9010198. PMID: 31941155; PMCID: PMC7017232.
[31] Perri G, Marchegiani G, Frigerio I, Dervenis CG, Conlon KC, Bassi C, Salvia R. Management of Pancreatic Cystic Lesions. Dig Surg. 2020;37(1):1-9. doi: 10.1159/000496509. Epub 2019 Jan 11. PMID: 30636253; PMCID: PMC7360492.
[32] Longevity OMAC. Retracted: Activation of PTEN/P13K/AKT Signaling Pathway by miRNA-124-3p-Loaded Nanoparticles to Regulate Oxidative Stress Attenuates Cardiomyocyte Regulation and Myocardial Injury. Oxid Med Cell Longev. 2023 Dec 29; 2023: 9768785. doi: 10.1155/2023/9768785. PMID: 38189020; PMCID: PMC10769672.
[33] Yang Y, Li J, Jing C, Zhai Y, Bai Z, Yang Y, Deng W. Inhibition of neuroactive ligand-receptor interaction pathway can enhance immunotherapy response in colon cancer: an in silico study. Expert Rev Anticancer Ther. 2023 Jul-Dec; 23(11):1205-1215. doi: 10.1080/14737140.2023.2245567. Epub 2023 Aug 24. PMID: 37555253.
[34] Hehr CL, Halabi R, McFarlane S. Spatial regulation of amacrine cell genesis by Semaphorin 3f. Dev Biol. 2022 Nov;491:66-81. doi: 10.1016/j.ydbio.2022.08.008. Epub 2022 Sep 2. PMID: 36058267.
[35] Zhang H, Wang Y, Qu M, Li W, Wu D, Cata JP, Miao C. Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis. Clin Transl Med. 2023 Jan;13(1):e1170. doi: 10.1002/ctm2.1170. PMID: 36629024; PMCID: PMC9832433.
[36] Fu Z, Chen S, Zhu Y, Zhang D, Xie P, Jiao Q, Chi J, Xu S, Xue Y, Lu X, Song X, Cristofanilli M, Gradishar WJ, Kalinsky K, Yin Y, Zhang B, Wan Y. Proteolytic regulation of CD73 by TRIM21 orchestrates tumor immunogenicity. Sci Adv. 2023 Jan 6;9(1):eadd6626. doi: 10.1126/sciadv.add6626. Epub 2023 Jan 6. PMID: 36608132; PMCID: PMC9821867.
[37] Zhang N, Aiyasiding X, Li WJ, Liao HH, Tang QZ. Neutrophil degranulation and myocardial infarction. Cell Commun Signal. 2022 Apr 11;20(1):50. doi: 10.1186/s12964-022-00824-4. PMID: 35410418; PMCID: PMC8996539.
[38] Huang X, Guan W, Xiang B, Wang W, Xie Y, Zheng J. MUC5B regulates goblet cell differentiation and reduces inflammation in a murine COPD model. Respir Res. 2022 Jan 18;23(1):11. doi: 10.1186/s12931-021-01920-8. PMID: 35042537; PMCID: PMC8764756.
[39] Shi Y, Qu Q, Wang C, He Y, Yang Y, Wu Y. Involvement of CYP2 and mitochondrial clan P450s of Helicoverpa armigera in xenobiotic metabolism. Insect Biochem Mol Biol. 2022 Jan;140:103696. doi: 10.1016/j.ibmb.2021.103696. Epub 2021 Nov 17. PMID: 34800643.
[40] Kimura S, Yokoyama S, Pilon AL, Kurotani R. Emerging role of an immunomodulatory protein secretoglobin 3A2 in human diseases. Pharmacol Ther. 2022 Aug;236:108112. doi: 10.1016/j. pharmthera. 2022.108112. Epub 2022 Jan 10. PMID: 35016921; PMCID: PMC9271138.
[41] He XS, Ye WL, Zhang YJ, Yang XQ, Liu F, Wang JR, Ding XL, Yang Y, Zhang RN, Zhao YY, Bi HX, Guo LC, Gan WJ, Wu H. Oncogenic potential of BEST4 in colorectal cancer via activation of PI3K/Akt signaling. Oncogene. 2022 Feb;41(8):1166-1177. doi: 10.1038/s41388-021-02160-2. Epub 2022 Jan 21. PMID: 35058597.
[42] Chong CH, Li Q, Mak PHS, Ng CCP, Leung EHW, Tan VH, Chan AKW, McAlonan G, Chan SY. Lrrc7 mutant mice model developmental emotional dysregulation that can be alleviated by mGluR5 allosteric modulation. Transl Psychiatry. 2019 Oct 3;9(1):244. doi: 10.1038/s41398-019-0580-9. PMID: 31582721; PMCID: PMC6776540.
[43] Sen P, Helmke A, Liao CM, Sörensen-Zender I, Rong S, Bräsen JH, Melk A, Haller H, von Vietinghoff S, Schmitt R. SerpinB2 Regulates Immune Response in Kidney Injury and Aging. J Am Soc Nephrol. 2020 May;31(5):983-995. doi: 10.1681/ASN.2019101085. Epub 2020 Mar 24. PMID: 32209589; PMCID: PMC7217424.
[44] Ma J, Li Q, Li Y. CircRNA PRH1-PRR4 stimulates RAB3D to regulate the malignant progression of NSCLC by sponging miR-877-5p. Thorac Cancer. 2022 Mar;13(5):690-701. doi: 10.1111/1759-7714.14264. Epub 2022 Jan 25. PMID: 35076987; PMCID: PMC8888154.
[45] Cai L, Tu M, Yin X, Zhang S, Zhuang W, Xia Y, Zhang Y, Zhang L, Yu L, Chi L, Huang Y. Combination of serum CST4 and DR-70 contributes to early diagnosis of colorectal cancer. Clin Chim Acta. 2022 Jun 1;531:318-324. doi: 10.1016/j.cca.2022.04.1000. Epub 2022 Apr 29. PMID: 35500878.
[46] Du X, Xia W, Fan W, Shen X, Wu H, Zhang H. Integrated Analysis of C16orf54 as a Potential Prognostic, Diagnostic, and Immune Marker across Pan-Cancer. Dis Markers. 2022 Sep 9;2022:9365046. doi: 10.1155/2022/9365046. PMID: 36118669; PMCID: PMC9481382.
[47] Xu T, Xu S, Yao Y, Chen X, Zhang Q, Zhao X, Wang X, Zhu J, Liu N, Zhang J, Lin Y, Zou J. P2RY14 downregulation in lung adenocarcinoma: a potential therapeutic target associated with immune infiltration. J Thorac Dis. 2022 Feb;14(2):515-535. doi: 10.21037/jtd-22-115. PMID: 35280459; PMCID: PMC8902120.
[48] Milart P, Paluszkiewicz P, Dobrowolski P, Tomaszewska E, Smolinska K, Debinska I, Gawel K, Walczak K, Bednarski J, Turska M, Raban M, Kocki T, Turski WA. Kynurenic acid as the neglected ingredient of commercial baby formulas. Sci Rep. 2019 Apr 15;9(1):6108. doi: 10.1038/s41598-019-42646-4. PMID: 30988385; PMCID: PMC6465401.
[49] Kumagai N, Baba R, Sakuma Y, Arita K, Shinohara M, Kourogi M, Fujimoto S, Fujita M. Origin of the apical transcytic membrane system in jejunal absorptive cells of neonates. Med Mol Morphol. 2011 Jun;44(2):71-8. doi: 10.1007/s00795-010-0506-3. Epub 2011 Jun 30. PMID: 21717309.
[50] Lokossou GAG, Kouakanou L, Schumacher A, Zenclussen AC. Human Breast Milk: From Food to Active Immune Response With Disease Protection in Infants and Mothers. Front Immunol. 2022 Apr 5;13:849012. doi: 10.3389/fimmu.2022.849012. PMID: 35450064; PMCID: PMC9016618.
[51] van Odijk J, Kull I, Borres MP, Brandtzaeg P, Edberg U, Hanson LA, et al.. Breastfeeding and Allergic Disease: A Multidisciplinary Review of the Literature (1966-2001) on the Mode of Early Feeding in Infancy and Its Impact on Later Atopic Manifestations. Allergy (2003) 58:833–43. doi: 10.1034/j.1398-9995.2003.00264.x
[52] Chen JR, Samuel HA, Shlisky J, Sims CR, Lazarenko OP, Williams DK, Andres A, Badger TM. A longitudinal observational study of skeletal development between ages 3 mo and 6 y in children fed human milk, milk formula, or soy formula. Am J Clin Nutr. 2023 Jun;117(6):1211-1218. doi: 10.1016/j. ajcnut. 2023.04.002. Epub 2023 Apr 5. PMID: 37028556.
[53] Chen JR, Lazarenko OP, Blackburn ML, Badeaux JV, Badger TM, Ronis MJ. Infant formula promotes bone growth in neonatal piglets by enhancing osteoblastogenesis through bone morphogenic protein signaling. J Nutr. 2009 Oct;139(10):1839-47. doi: 10.3945/jn.109.109041. Epub 2009 Aug 26. PMID: 19710159.