• الصفحة الرئيسية
  • اهمیت اسیدهای چرب زنجیر کوتاه سنتز شده توسط میکروارگانیسم‌‌های روده، به عنوان یک عامل اپی ژنتیک، در کاهش ابتلا به سرطان کولون

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رقم المقالة : SJOAPB-2210-1396 (R1) زيارة : 312 الصفحة: 59 - 86

نوع المخطوط: ابحاث

اهمیت اسیدهای چرب زنجیر کوتاه سنتز شده توسط میکروارگانیسم‌‌های روده، به عنوان یک عامل اپی ژنتیک، در کاهش ابتلا به سرطان کولون

الموضوعات :

شیوا دارابی 1 ( دانشجوی دکتری بیوشیمی، گروه زیست‌شناسی، واحد سنندج، دانشگاه آزاد اسلامی، سنندج، ایران. )
فاطمه کشاورزی 2 ( دانشیار، گروه زیست‌شناسی، واحد سنندج، دانشگاه آزاد اسلامی، سنندج، ایران )
پرویز اشتری 3 ( دانشیار، دانشکده تحقیقات کاربردی پرتو، پژوهشکده علوم و فناوری هسته‌ای، کرج، ایران )
فرحناز معتمدی سده 4 ( دانشیار، گروه دامپزشکی و علوم دامی، مرکز تحقیقات کشاورزی هسته‌ای، پژوهشکده علوم و فناوری هسته‌ای، کرج، ایران. )
بهروز علیرضاپور 5 ( دانشیار، مرکز تحقیقات کاربردی پرتو، پژوهشکده علوم و فناوری هسته‌ای، تهران، ایران. )

تاريخ الإرسال : 09 الأحد , رمضان, 1443 تاريخ التأكيد : 07 الإثنين , ذو القعدة, 1443 تاريخ الإصدار : 23 الأربعاء , ذو القعدة, 1443

الکلمات المفتاحية: فاکتورهای اپی ژنتیک, رژیم غذایی, اسیدهای چرب زنجیره کوتاه (SCFAs), سرطان کولون,  میکروبیوتای روده,

ملخص المقالة :

هدف: مکانیسم‌های درگیر در پاتوژنز سرطان کولورکتال هنوز به درستی شناخته نشده‌اند، اما رژیم غذایی فاکتور اصلی است که اثرات چند جانبه‌ای از جمله تغییر در متابولوم و ترانسکریپتوم میزبان دارد. متابولیت‌‌هایی که از رژیم غذایی حاصل می‌‌شوند، می‌‌توانند به طور مستقیم بر متابولیسم کل بدن تاثیر بگذارند. هدف پژوهش حاضر، مرور تاثیر میکروبیوتای روده به واسطه سنتز اسیدهای چرب زنجیره کوتاه (استات، بوتیرات و پروپیونات)، و در نتیجه القای بیان ژن سیتوکروم P4501A1 در پیشگیری و درمان سرطان کولون است.مواد و روش‌ها: با استفاده از کلمات کلیدی، جستجو و جمع‌آوری مقالات از پایگاه‌های اطلاعاتی و استنادی پابمد (PubMed)، آی.‌ اس. آی. ‌(ISI web of Knowledge)، اسکوپوس (SCOPUS)، گوگل‌ اسکالر (Google Scholar)، پروکوئست‌(ProQuest) ، اکسفورد (Oxford) و اویدو(Ovid) و نیز معروف‌ترین‌ پایگاه‌های اطلاعاتی داخلی شامل پایگاه جهاد دانشگاهی (SID)، ایرانمدکس ‌(Iranmedex)، مگیران (Magiran)، ایرانداک (Irandoc) و مدلیب‌(MedLib) انجام شد.یافته‌ها: مواد ترکیبات غذایی هضم نشده که وارد روده بزرگ می‌‌شوند، توسط میکروبیوتای روده تخمیر شده و متابولیت‌‌های تخمیری تولید می‌‌شود که طیف گسترده‌ای از عملکرد‌‌های موثر را انجام می‌‌دهند. برخی از این متابولیت‌‌ها با سیستم ایمنی روده تعامل دارند، از جمله اسید‌‌های چرب زنجیره کوتاه، لیگاند‌‌های گیرنده آریل هیدروکربن و متابولیت‌‌های اسید‌‌‌‌های صفراوی که در القای هموستاز ایمنی روده نقش دارند. به نظر می‌‌رسد که اثرات حفاظتی اسید‌‌های چرب زنجیره کوتاه سنتز شده توسط میکروارگانیسم‌ها، در سرطان کولون به واسطه مهار فعالیت هیستون د‌‌استیلازی و تقویت گیرنده آریل هیدروکربن و در نتیجه حفاظت از DNA در برابر آسیب‌های ناشی از کارسینوژن‌ها، با فعال‌سازی آنزیم‌‌‌های متابولیزه‌کننده زنوبیوتیک، مانند سیتوکروم P4501A1، اعمال شود.نتیجه‌گیری: پژوهش حاضر دیدگاه جدیدی را در رابطه با اهمیت میکروبیوتا روده به واسطه تولید اسیدهای چرب زنجیره کوتاه به ویژه استات، بوتیرات و پروپیونات به عنوان اهداف دارویی در جهت پیشگیری و حتی درمان سرطان کلورکتال ارائه داد.

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_||_

  1. Zheng P, Li Zh & Zhou Zh. Gut microbiome in type 1 diabetes: A comprehensive review. Diabetes Metab Res Rev. 2018; 34: e3043. DOI:org/10.1002/dmrr.3043
    2.
  2. Poppe J, Baarle L, Matteoli G & Verbeke K. How microbial food fermentation supports a tolerant gut. Molecular Nutrition & Food Research. 2020. DOI: 1002/mnfr.202000036
    3.
  3. Mayer EA, Savidge T & Shulman RJ. Brain-gut microbiome interactions and functional bowel disorders. Gastroenterology. 2014; 146:1500-12.
    DOI: 1053/j.gastro.2014.02.037
    4.
  4. Macfarlane, GT & Macfarlane, S. Bacteria,colonic fermentation and gastro intestinal health. AOAC Int. 2012; 95: 50-60.
    5.
  5. Xu W, Zhou Y & Hang X, Shen D. Current evidence on the relationship between CYP1B1 polymorphisms and lung cancer risk: a metaanalysis. Mol Biol Rep. 2012; 39(3): 2821-9.
    6.
  6. Beyerle J, Frei E, Stiborov M, Habermann N & Ulrich CM. Biotransformation of xenobiotics in the human colon and rectum and its association with colorectal cancer. Drug Metab Rev; 2015; 47: 199-221.
    7.
  7. Gutierrez-Vazquez C & Quintana FJ. Regulation of the immune response by the aryl hydrocarbon receptor. Immunity. 2018; 48(1): 19-33.
    8.
  8. Donaldson GP, Lee SM & Mazmanian SK. Gut biogeography of the bacterial microbiota. Nature reviews. Microbiology. 2016; 14(1): 20-32.
    9.
  9. Li H & et al. The outer mucus layer hosts a distinct intestinal microbial niche. Nature Communications. 2015; 6(1): 8292.
    10.
  10. Franzosa EA & et al. Identifying personal microbiomes using metagenomic codes. Proceedings of the National Academy of Sciences of the United States of America. 2015; 112(22): 2930-8.
    11.
  11. Costea PI & et al. Enterotypes in the landscape of gut microbial community composition. Nature Microbiology. 2017; 3(1): 8-16.
    12.
  12. Ha CW, Lam YY & Holmes AJ. Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health. World Journal of Gastroenterology. 2014; 20(44): 16498-16517.
    13.
  13. Marinelli L, Martin-Gallausiaux C, Bourhis J-M, B_eguet-Crespel F, Blotti_ere HM & Lapaque N. Identification of the novel role of butyrate as Ahr ligand in human intestinal epithelial cells. Sci Rep. 2019; 9(1): 643.
    14.
  14. Van der Beek CM & et al. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin Sci (Lond). 2016; 130(22): 2073-2082. DOI:1042/CS20160263
    15.
  15. Louis P, Hold G & Flint HJ.The gut microbiota, bacterial metabolites and colorectal cancer. Rev.Microbiol. 2014; 12: 661-672. DOI: 10.1038/nrmicro3344
    16.
  16. Reichardt N & et al. Phylogenetic distribution of three pathways forpropionate production within the human gut microbiota. ISMEJ. 2014; 8: 1323-1335.
    DOI:1038/ismej.2014.14
    17.
  17. Flint HJ, Duncan SH, Scott KP, & Louis P. Links between diet, gut microbiota composition and gut Proc.Nutr.Soc. 2015; 74:13-22.
    DOI: 10.1017/s0029665114001463
    18.
  18. Machiels K, & et al. Adecrease of the butyrate-producing species Roseburiahominis and Faecali bacterium prausnitzii defines dysbiosis in patients with Gut. 2014; 63:1275-1283. DOI: 10.1136/gutjnl-2013-304833.
    19.
  19. Nedjadi T, Moran, AW, Al-Rammahi MA & Shirazi-Beechey SP. Characterization of butyrate transport across the luminal membranes of equine large intestine. Exp Physiol. 2014; 99(10): 1335-1347.
    20.
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    21.
  21. Macfarlane GT & Macfarlane S. Bacteria,colonic fermentation and gastro intestinal health. AOACInt. 2012; 95: 50-60.
    22.
  22. Jung TH, Park JH, Jeon WM & Han KS. Butyrate modulates bacterial adherence on LS174T human colorectal cells by stimulating mucin secretionand MAPK signaling pathway. Res.Pract. 2015; 9: 343-349. DOI: 10.4162/nrp.2015.9.4.343
    23.
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    24.
  24. Canfora EE., Jocken JW. & Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Rev.Endocrinol. 2015, 11: 577-591.     
    DOI: 10.1038/nrendo.2015.128.
    25.
  25. Keku TO, Dulal S, Deveaux A, Jovov, B & Han X. The gastro intestinal microbiota and colorectal cancer. J. Physiol. Gastrointest. LiverPhysiol. 2015, 308: G351-G363.
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    26.
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    27.
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    28.
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    29.
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    30.
  30. Han A, Bennett N, Macdonald A, Johnstone M, Whelan J & Donohoe DR. Cellular metabolism and dose reveal carnitine‐dependent and ‐independent mechanisms of butyrate oxidation in colorectal cancer cells. Journal of Cellular Physiology. 2016; 231: 1804-1813.
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  33. Binoy Shivanna, Ch Ch & Bhagavatula M. The Aryl Hydrocarbon Receptor (AHR): A Novel Therapeutic Target for Pulmonary Diseases? J. Mol. Sci. 2022; 23: 1516.
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    36.
  36. Roager HM & Licht TR. Microbial tryptophan catabolites in health and disease. Commun. 2018; 9: 3294.
    37.
  37. Korecka A & et al. Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism. NPJ Biofilms Microbiomes. 2016; 2: 16014.
    38.
  38. Cibrian D & et al. CD69 controls the uptake of L-tryptophan through LAT1-CD98 and AhR-dependent secretion of IL-22 in psoriasis. Immunol. 2016; 17: 985-996.
    39.
  39. Vyhlídalová B & et al. Gut Microbial Catabolites of Tryptophan Are Ligands and Agonists of the Aryl Hydrocarbon Receptor: A Detailed Characterization. J. Mol. Sci. 2020; 21: 2614.
    40.
  40. Zhang M & et al. The Chinese medicinal herb decoction QRZSLXF enhances anti-inflammatory e_ect in TNBS-induced colitis via balancing Th17/Tregs J. Ethnopharmacol. 2020; 251: 112549.
    41.
  41. Jin UH & et al. Short Chain Fatty Acids Enhance Aryl Hydrocarbon (Ah) Responsiveness in Mouse Colonocytes and Caco-2 Human Colon Cancer Cells. Rep. 2017; 7: 10163.
    42.
  42. Piper CJM & et al. Aryl Hydrocarbon Receptor Contributes to the Transcriptional Program of IL-10 Producing Regulatory B Cells. Cell Rep. 2019; 29: 1878-1892.e7.
    43.
  43. Manzella CR & et al. Serotonin Modulates AhR Activation by Interfering with CYP1A1-Mediated Clearance of AhR Ligands. Cell Physiol. Biochem. 2020; 54: 126-141.
    44.
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