|
|
|
| Association between micronutrients and irritable bowel syndrome: a Mendelian randomization study |
| ZHANG Yuanyuan1,2, XU Hexiang3, LI Ming1,2
|
1. Department of Anorectal Diseases, The First Affiliated Hospital of Anhui University of Chinese Medical, Hefei, Anhui 230601, China;
2. Department of Anorectal Diseases, Shanghai University of Traditional Chinese Medicine Affiliated Shuguang Hospital Anhui Hospital, Hefei, Anhui 230031, China;
3. Department of Infectious Diseases, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230061, China |
|
|
|
|
Abstract Objective To explore the causal association between micronutrients and irritable bowel syndrome (IBS) using a Mendelian randomization (MR) method, so as to provide the evidence for formulating prevention and treatment measures for IBS. Methods Genome-wide association studies (GWAS) summary data for 14 micronutrients (copper, selenium, zinc, iron, magnesium, calcium, potassium, folate, vitamin C, vitamin D, vitamin E, vitamin B6, vitamin B12, and carotene) were collected from the MRC Integrative Epidemiology Unit at the University of Bristol GWAS data and the UK Biobank data. GWAS data for IBS were obtained from the FinnGen R10 database. A bidirectional two-sample MR analysis was conducted to assess the causal relationships between micronutrients and IBS, with the inverse-variance weighted method as the primary analytical approach. Heterogeneity among instrumental variables was evaluated using Cochran's Q test. Horizontal pleiotropy was assessed via MR-Egger regression and the MR-PRESSO test. The robustness of the results was examined using leave-one-out and funnel plot. Results Forward MR analysis revealed a statistically significant association between vitamin B12 and IBS (OR=1.523, 95%CI: 1.093-2.213), while no significant associations were observed for the other 13 micronutrients (all P>0.05). Reverse MR analysis showed no significant association between IBS and any of the 14 micronutrients (all P>0.05). Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among the instrumental variables (all P>0.05). The robustness of the findings was supported by leave-one-out and funnel plot. Conclusion Higher vitamin B12 level is associated with an increased risk of IBS, but no reverse causal relationship between vitamin B12 and IBS has been found.
|
|
Received: 09 January 2025
Revised: 09 March 2025
Published: 16 April 2025
|
|
|
|
|
|
[1] SPERBER A D,BANGDIWALA S I,DROSSMAN D A,et al.Worldwide prevalence and burden of functional gastrointestinal disorders,results of Rome Foundation Global Study[J].Gastroenterology,2021,160(1):99-114.
[2] FORD A C,SPERBER A D,CORSETTI M,et al.Irritable bowel syndrome[J].Lancet,2020,396(10263):1675-1688.
[3] HE Z X,CHEN H N,CHEN Y,et al.Selenium deficiency induces irritable bowel syndrome:analysis of UK Biobank data and experimental studies in mice[J/OL].Ecotoxicol Environ Saf,2024,281[2025-03-09].https://doi.org/10.1016/j.ecoenv.2024.116604.
[4] BEK S,TEO Y N,TAN X H,et al.Association between irritable bowel syndrome and micronutrients:a systematic review[J].J Gastroenterol Hepatol,2022,37(8):1485-1497.
[5] ROTH B,LARSSON E,OHLSSON B.Poor intake of vitamins and minerals is associated with symptoms among patients with irritable bowel syndrome[J].J Gastroenterol Hepatol,2022,37(7):1253-1262.
[6] SKRIVANKOVA V W,RICHMOND R C,WOOLF B A R,et al.Strengthening the reporting of observational studies in epidemiology using Mendelian randomization:the STROBE-MR Statement[J].JAMA,2021,326(16):1614-1621.
[7] BOWDEN J,HOLMES M V.Meta-analysis and Mendelian randomization:a review[J].Res Synth Methods,2019,10(4):486-496.
[8] ADAMS J F,ROSS S K,MERVYN L,et al.Absorption of cyanocobalamin,coenzyme B12,methylcobalamin,and hydroxocobalamin at different dose levels[J].Scand J Gastroenterol,1971,6(3):249-252.
[9] KIM J Y,SONG M,KIM M S,et al.An atlas of associations between 14 micronutrients and 22 cancer outcomes:Mendelian randomization analyses[J].BMC Med,2023,21(1):1-12.
[10] TSILIDIS K K,PAPADIMITROU N,DIMOU N,et al.Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent:a Mendelian randomization study[J].Am J Clin Nutr,2021,113(6):1490-1502.
[11] YANG H,SONG J,LI A,et al.Genetically predicted levels of folate,vitamin B12,and risk of autoimmune diseases:a Mendelian randomization study[J/OL].Front Immunol,2023,14[2025-03-09].https://doi.org/10.3389/fimmu.2023.1139799.
[12] BENIGHT N M,STOLL B,CHACKO S,et al.B-vitamin deficiency is protective against DSS-induced colitis in mice[J].Am J Physiol Gastrointest Liver Physiol,2011,301(2):249-259.
[13] HOSSAIN K S,AMARASENA S,MAYENGBAM S.B vitamins and their roles in gut health[J/OL].Microorganisms,2022[2025-03-09].https://doi.org/10.3390/microorganisms10061168.
[14] KELLY C J,ALEXEEV E E,FARB L,et al.Oral vitamin B12 supplement is delivered to the distal gut,altering the corrinoid profile and selectively depleting Bacteroides in C57BL/6 mice[J].Gut Microbes,2019,10(6):654-662.
[15] ROTH B,OHLSSON B.Overweight and vitamin D deficiency are common in patients with irritable bowel syndrome:a cross-sectional study[J].BMC Gastroenterol,2024,24(1):296-311.
[16] BAHRAMI A,GONOODI K,KHAYYATZADEH S S,et al.The association of trace elements with premenstrual syndrome,dysmenorrhea and irritable bowel syndrome in adolescents[J].Eur J Obstet Gynecol Reprod Biol,2019,233:114-119.
[17] LIGAARDEN S C,FARUP P G.Low intake of vitamin B6 is associated with irritable bowel syndrome symptoms[J].Nutr Res,2011,31(5):356-361. |
|
|
|
