Skip to content
2000
image of Exploring the Diet-diverticular Disease Link: Insights from a Comprehensive Mendelian Randomization Study

Abstract

Background

The interplay between dietary habits and the development of Diverticular Disease (DD) has long been a subject of vibrant debate.

Objective

Utilizing Mendelian Randomization (MR), this study aims to meticulously examine the causal dynamics at play.

Methods

The foundation for the Genome-Wide Association Studies (GWAS) on DD was established using a dataset from the FinnGen consortium, encompassing 33,619 patients and 329,381 control participants. Data on 18 dietary habits and DD for the validation cohort were procured from the UK Biobank. An MR analysis was executed to delve into the causal relationship between dietary habits and DD, adhering to a rigorous Bonferroni correction threshold of 3.00E-03. Our main analysis method was the Inverse Variance Weighted (IVW) approach. To improve the accuracy and reliability of our study, we also conducted heterogeneity analysis, tests for horizontal pleiotropy, outlier identification, and “leave-one-out” sensitivity analysis.

Results

Our analysis unearthed a potential causal association between the consumption of dried fruits and a lower risk of developing DD (IVW: odds ratio (OR) 0.372, 95% confidence interval (CI) 0.272 - 0.509, = 5.79E-10), a finding that was corroborated in the validation cohort (IVW: OR 0.975, 95% CI 0.961 - 0.990, = 1.04E-03). Conversely, our results do not substantiate a causal link between the consumption of alcohol, dietary fiber, and red meat and the risk of DD.

Conclusion

Our detailed MR analyses show that eating dried fruit lowers the risk of DD, providing strong support for prevention and treatment approaches for DD.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673342480250203111209
2025-02-18
2025-04-01
Loading full text...

Full text loading...

References

  1. Bhatia M. Mattoo A. Diverticulosis and diverticulitis: Epidemiology, pathophysiology, and current treatment trends. Cureus 2023 15 8 e43158 37565180
    [Google Scholar]
  2. Mali J. Mentula P. Leppäniemi A. Sallinen V. Determinants of treatment and outcomes of diverticular abscesses. World J. Emerg. Surg. 2019 14 1 31 10.1186/s13017‑019‑0250‑5 31320921
    [Google Scholar]
  3. Coakley K.M. Davis B.R. Kasten K.R. Complicated diverticular disease. Clin. Colon Rectal Surg. 2021 34 2 096 103 10.1055/s‑0040‑1716701 33642949
    [Google Scholar]
  4. Peery A.F. Crockett S.D. Murphy C.C. Jensen E.T. Kim H.P. Egberg M.D. Lund J.L. Moon A.M. Pate V. Barnes E.L. Schlusser C.L. Baron T.H. Shaheen N.J. Sandler R.S. Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: Update 2021. Gastroenterology 2022 162 2 621 644 10.1053/j.gastro.2021.10.017 34678215
    [Google Scholar]
  5. Böhm S.K. Risk factors for diverticulosis, diverticulitis, diverticular perforation, and bleeding: A plea for more subtle history taking. Viszeralmedizin 2015 31 2 84 94 26989377
    [Google Scholar]
  6. Weizman A.V. Nguyen G.C. Diverticular disease: Epidemiology and management. Can. J. Gastroenterol. 2011 25 7 385 389 10.1155/2011/795241 21876861
    [Google Scholar]
  7. Painter N.S. Burkitt D.P. Diverticular disease of the colon: A deficiency disease of Western civilization. BMJ 1971 2 5759 450 454 10.1136/bmj.2.5759.450 4930390
    [Google Scholar]
  8. Strate L.L. Lifestyle factors and the course of diverticular disease. Dig. Dis. 2012 30 1 35 45 10.1159/000335707 22572683
    [Google Scholar]
  9. Manousos O.N. Vrachliotis G. Papaevangelou G. Detorakis E. Doritis P. Stergiou L. Merikas G. Relation of diverticulosis of the colon to environmental factors in Greece. Am. J. Dig. Dis. 1973 18 3 174 176 10.1007/BF01071969 4688568
    [Google Scholar]
  10. Lin O.S. Soon M.S. Wu S.S. Chen Y.Y. Hwang K.L. Triadafilopoulos G. Dietary habits and right-sided colonic diverticulosis. Dis. Colon Rectum 2000 43 10 1412 1418 10.1007/BF02236638 11052519
    [Google Scholar]
  11. Song J.H. Kim Y.S. Lee J.H. Ok K.S. Ryu S.H. Lee J.H. Moon J.S. Clinical characteristics of colonic diverticulosis in Korea: A prospective study. Korean J. Intern. Med. (Korean. Assoc. Intern. Med.) 2010 25 2 140 146 10.3904/kjim.2010.25.2.140 20526386
    [Google Scholar]
  12. Peery A.F. Barrett P.R. Park D. Rogers A.J. Galanko J.A. Martin C.F. Sandler R.S. A high-fiber diet does not protect against asymptomatic diverticulosis. Gastroenterology 2012 142 2 266 272.e1 10.1053/j.gastro.2011.10.035 22062360
    [Google Scholar]
  13. Peery A.F. Sandler R.S. Ahnen D.J. Galanko J.A. Holm A.N. Shaukat A. Mott L.A. Barry E.L. Fried D.A. Baron J.A. Constipation and a low-fiber diet are not associated with diverticulosis. Clin. Gastroenterol. Hepatol. 2013 11 12 1622 1627 10.1016/j.cgh.2013.06.033 23891924
    [Google Scholar]
  14. Schoepf D. Heun R. Alcohol dependence and physical comorbidity: Increased prevalence but reduced relevance of individual comorbidities for hospital-based mortality during a 12.5-year observation period in general hospital admissions in urban North-West England. Eur. Psychiatry 2015 30 4 459 468 10.1016/j.eurpsy.2015.03.001 25841661
    [Google Scholar]
  15. Nagata N. Niikura R. Shimbo T. Kishida Y. Sekine K. Tanaka S. Aoki T. Watanabe K. Akiyama J. Yanase M. Itoh T. Mizokami M. Uemura N. Alcohol and smoking affect risk of uncomplicated colonic diverticulosis in Japan. PLoS One 2013 8 12 e81137 10.1371/journal.pone.0081137 24339905
    [Google Scholar]
  16. Aldoori W.H. Giovannucci E.L. Rimm E.B. Wing A.L. Trichopoulos D.V. Willett W.C. A prospective study of alcohol, smoking, caffeine, and the risk of symptomatic diverticular disease in men. Ann. Epidemiol. 1995 5 3 221 228 10.1016/1047‑2797(94)00109‑7 7606311
    [Google Scholar]
  17. Crowe F.L. Appleby P.N. Allen N.E. Key T.J. Diet and risk of diverticular disease in Oxford cohort of European prospective investigation into cancer and nutrition (EPIC): Prospective study of British vegetarians and non-vegetarians. BMJ 2011 343 jul19 4 d4131 10.1136/bmj.d4131 21771850
    [Google Scholar]
  18. Cao Y. Strate L.L. Keeley B.R. Tam I. Wu K. Giovannucci E.L. Chan A.T. Meat intake and risk of diverticulitis among men. Gut 2018 67 3 466 472 10.1136/gutjnl‑2016‑313082 28069830
    [Google Scholar]
  19. Strate L.L. Liu Y.L. Syngal S. Aldoori W.H. Giovannucci E.L. Nut, corn, and popcorn consumption and the incidence of diverticular disease. JAMA 2008 300 8 907 914 10.1001/jama.300.8.907 18728264
    [Google Scholar]
  20. Emdin C.A. Khera A.V. Kathiresan S. Mendelian randomization. JAMA 2017 318 19 1925 1926 10.1001/jama.2017.17219 29164242
    [Google Scholar]
  21. Davey Smith G. Ebrahim S. ‘Mendelian randomization’: Can genetic epidemiology contribute to understanding environmental determinants of disease? Int. J. Epidemiol. 2003 32 1 1 22 10.1093/ije/dyg070 12689998
    [Google Scholar]
  22. Davey Smith G. Hemani G. Mendelian randomization: Genetic anchors for causal inference in epidemiological studies. Hum. Mol. Genet. 2014 23 R1 R89 R98 10.1093/hmg/ddu328 25064373
    [Google Scholar]
  23. Burgess S. Labrecque J.A. Mendelian randomization with a binary exposure variable: Interpretation and presentation of causal estimates. Eur. J. Epidemiol. 2018 33 10 947 952 10.1007/s10654‑018‑0424‑6 30039250
    [Google Scholar]
  24. Sudlow C. Gallacher J. Allen N. Beral V. Burton P. Danesh J. Downey P. Elliott P. Green J. Landray M. Liu B. Matthews P. Ong G. Pell J. Silman A. Young A. Sprosen T. Peakman T. Collins R. UK biobank: An open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015 12 3 e1001779 10.1371/journal.pmed.1001779 25826379
    [Google Scholar]
  25. Burgess S. Thompson S.G. CRP CHD Genetics Collaboration Avoiding bias from weak instruments in Mendelian randomization studies. Int. J. Epidemiol. 2011 40 3 755 764 10.1093/ije/dyr036 21414999
    [Google Scholar]
  26. Bowden J. Del Greco M F. Minelli C. Davey Smith G. Sheehan N.A. Thompson J.R. Assessing the suitability of summary data for two-sample Mendelian randomization analyses using MR-Egger regression: The role of the I2 statistic. Int. J. Epidemiol. 2016 45 6 dyw220 10.1093/ije/dyw220 27616674
    [Google Scholar]
  27. Broadbent J.R. Foley C.N. Grant A.J. Mason A.M. Staley J.R. Burgess S. MendelianRandomization v0.5.0: Updates to an R package for performing Mendelian randomization analyses using summarized data. Wellcome Open Res. 2020 5 252 10.12688/wellcomeopenres.16374.2 33381656
    [Google Scholar]
  28. Hemani G. Zheng J. Elsworth B. Wade K.H. Haberland V. Baird D. Laurin C. Burgess S. Bowden J. Langdon R. Tan V.Y. Yarmolinsky J. Shihab H.A. Timpson N.J. Evans D.M. Relton C. Martin R.M. Davey Smith G. Gaunt T.R. Haycock P.C. The MR-Base platform supports systematic causal inference across the human phenome. eLife 2018 7 e34408 10.7554/eLife.34408 29846171
    [Google Scholar]
  29. Burgess S. Butterworth A. Thompson S.G. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet. Epidemiol. 2013 37 7 658 665 10.1002/gepi.21758 24114802
    [Google Scholar]
  30. Zhao J. Ming J. Hu X. Chen G. Liu J. Yang C. Bayesian weighted Mendelian randomization for causal inference based on summary statistics. Bioinformatics 2020 36 5 1501 1508 10.1093/bioinformatics/btz749 31593215
    [Google Scholar]
  31. Bowden J. Davey Smith G. Haycock P.C. Burgess S. Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet. Epidemiol. 2016 40 4 304 314 10.1002/gepi.21965 27061298
    [Google Scholar]
  32. Bowden J. Hemani G. Davey Smith G. Invited commentary: Detecting individual and global horizontal pleiotropy in mendelian randomization—a job for the humble heterogeneity statistic? Am. J. Epidemiol. 2018 187 12 2681 2685 10.1093/aje/kwy185 30188969
    [Google Scholar]
  33. van Kippersluis H. Rietveld C.A. Pleiotropy-robust Mendelian randomization. Int. J. Epidemiol. 2018 47 4 1279 1288 10.1093/ije/dyx002 28338774
    [Google Scholar]
  34. Chen L. Yang H. Li H. He C. Yang L. Lv G. Insights into modifiable risk factors of cholelithiasis: A Mendelian randomization study. Hepatology 2022 75 4 785 796 10.1002/hep.32183 34624136
    [Google Scholar]
  35. Hong J. Qu Z. Ji X. Li C. Zhang G. Jin C. Wang J. Zhang Y. Shen Y. Meng J. Zhou C. Fang C. Wang W. Yan S. Genetic associations between IL-6 and the development of autoimmune arthritis are gender-specific. Front. Immunol. 2021 12 707617 10.3389/fimmu.2021.707617 34539640
    [Google Scholar]
  36. Tursi A. Elisei W. Colonic diverticulosis and diet: Is it useful? Polish Archives of Internal Medicine 2020 130 3 232 239 10.20452/pamw.15199 32077444
    [Google Scholar]
  37. Alasalvar C. Salvadó J.S. Ros E. Bioactives and health benefits of nuts and dried fruits. Food Chem. 2020 314 126192 10.1016/j.foodchem.2020.126192 31958750
    [Google Scholar]
  38. Vinson J.A. Zubik L. Bose P. Samman N. Proch J. Dried fruits: Excellent in vitro and in vivo antioxidants. J. Am. Coll. Nutr. 2005 24 1 44 50 10.1080/07315724.2005.10719442 15670984
    [Google Scholar]
  39. Chang S.K. Alasalvar C. Shahidi F. Review of dried fruits: Phytochemicals, antioxidant efficacies, and health benefits. J. Funct. Foods 2016 21 113 132 10.1016/j.jff.2015.11.034
    [Google Scholar]
  40. Rababah T.M. Ereifej K.I. Howard L. Effect of ascorbic acid and dehydration on concentrations of total phenolics, antioxidant capacity, anthocyanins, and color in fruits. J. Agric. Food Chem. 2005 53 11 4444 4447 10.1021/jf0502810 15913308
    [Google Scholar]
  41. Hernández-Alonso P. Camacho-Barcia L. Bulló M. Salas-Salvadó J. Nuts and dried fruits: An update of their beneficial effects on type 2 diabetes. Nutrients 2017 9 7 673 10.3390/nu9070673 28657613
    [Google Scholar]
  42. Folsom A.R. Hong C.P. Magnesium intake and reduced risk of colon cancer in a prospective study of women. Am. J. Epidemiol. 2006 163 3 232 235 10.1093/aje/kwj037 16319289
    [Google Scholar]
  43. van den Brandt P.A. Smits K.M. Goldbohm R.A. Weijenberg M.P. Magnesium intake and colorectal cancer risk in the netherlands cohort study. Br. J. Cancer 2007 96 3 510 513 10.1038/sj.bjc.6603577 17285123
    [Google Scholar]
  44. d’Unienville N.M.A. Hill A.M. Coates A.M. Yandell C. Nelson M.J. Buckley J.D. Effects of almond, dried grape and dried cranberry consumption on endurance exercise performance, recovery and psychomotor speed: Protocol of a randomised controlled trial. BMJ Open Sport Exerc. Med. 2019 5 1 e000560 10.1136/bmjsem‑2019‑000560 31548903
    [Google Scholar]
  45. Tian B. Zhang Z. Zhao J. Ma Q. Liu H. Nie C. Ma Z. An W. Li J. Dietary whole Goji berry ( Lycium barbarum ) intake improves colonic barrier function by altering gut microbiota composition in mice. Int. J. Food Sci. Technol. 2021 56 1 103 114 10.1111/ijfs.14606
    [Google Scholar]
  46. Barbara G. Scaioli E. Barbaro M.R. Biagi E. Laghi L. Cremon C. Marasco G. Colecchia A. Picone G. Salfi N. Capozzi F. Brigidi P. Festi D. Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease. Gut 2017 66 7 1252 1261 10.1136/gutjnl‑2016‑312377 27618836
    [Google Scholar]
  47. Lou T. Huang W. Wu X. Wang M. Zhou L. Lu B. Zheng L. Hu Y. Monitoring, exposure and risk assessment of sulfur dioxide residues in fresh or dried fruits and vegetables in China. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 2017 34 6 918 927 10.1080/19440049.2017.1313458 28357931
    [Google Scholar]
  48. Rentschler H. [Sulfur dioxide in dried fruit]. Mitt. Geb. Lebensmittelunters. Hyg. 1951 42 3 275 279 [Sulfur dioxide in dried fruit]. 14863309
    [Google Scholar]
  49. Stadtman E.R. Barker H.A. Mrak E.M. Mackinney G. Storage of dried fruit; influence of moisture and sulfur dioxide on deterioration of apricots. Ind. Eng. Chem. 1946 38 1 99 104 10.1021/ie50433a038 21008317
    [Google Scholar]
  50. Liao B.S. Sram J.C. Files D.J. Determination of free sulfites (SO3-2) in dried fruits processed with sulfur dioxide by ion chromatography through anion exchange column and conductivity detection. J. AOAC Int. 2013 96 5 1103 1108 10.5740/jaoacint.11‑053 24282955
    [Google Scholar]
  51. Sharara A.I. El-Halabi M.M. Mansour N.M. Malli A. Ghaith O.A. Hashash J.G. Maasri K. Soweid A. Barada K. Mourad F.H. El Zahabi L. Alcohol consumption is a risk factor for colonic diverticulosis. J. Clin. Gastroenterol. 2013 47 5 420 425 10.1097/MCG.0b013e31826be847 23164685
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673342480250203111209
Loading
/content/journals/cmc/10.2174/0109298673342480250203111209
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test