Study On The Relationship Between Vitamin D,gut Microbiota And Risk For Colorectal Cancer

Colorectal cancer is the most common malignant tumor in our country,and its incidence is increasing in recent years.To take effective measures for the cause of the disease is expected to significantly reduce its incidence and disease burden.However,the etiology of colorectal cancer has not been clarified.A large number of studies have indicated that the incidence of colorectal cancer is the result of the comprehensive function of environmental and genetic factors,intestinal flora,diet and other environmental factors play an important role in the occurrence of colorectal cancer.Previous studies have indicated that vitamin D may be a protective factor for colorectal cancer,but the results are not consistent with the previous studies.Current studies suggest that colorectal cancer is a disease associated with intestinal flora.Intestinal flora may play an intermediary role in the relationship between diet and colorectal cancer.Preliminary findings suggest that dietary structure may significantly affect the structure and function of intestinal micro ecology,thus affecting the risk of colorectal cancer.In summary,we hypothesized that gut flora may be an important factor in the relationship between vitamin D and colorectal cancer.Therefore,this study carried out the following research to verify the above assumptions.Aims:Study on the relationship between Vitamin D,intestinal flora and risk for colorectal cancer.Methods:Measure the concentrations of plasma 25-hydroxyvitamin D of the two groups by ELISAs.Detect vitamin D receptor expression of colorectal cancer tissue and pericarcinous tissue by Immunohistochemistry and bacterial 16 S rDNA V3-V4 district of stool specimens by high-throughput sequencing so as to evaluate the structure of intestinal flora.Apply stratification analysis according to the lesion site(proximal colon,distal colon)and structure of intestinal flora(abundance and diversity)to compare the plasma vitamin D level of the two groups by case-control study.Investigate the expression of vitamin D receptor,the structure of intestinal flora and colorectal cancer incidence by case-case-control study.Based on the analysis results above,to explore and verify the relationship between vitamin D and colorectal cancer.Use t test or χ2 test for single factor,and logistic regression.Result:1、The relationship between vitamin D and colorectal cancer(1)Colorectal cancer group and healthy control group plasma 25-Hydroxy Vitamin D levelsUnivariate analysis showed that there was no significant difference between the two groups of plasma 25-hydroxyl vitamin D levels(P=0.213).Multivariate results display in control plasma sTNFR2,endotoxin,the dietary intake of fruits and vegetables,red meat intake,intake of garlic,pickled food intake factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / m L)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/mL relative risk(95% CI)were 1.09(0.48,2.48)and 0.73(0.30,1.76).The results showed that the plasma levels of 25-Hydroxy Vitamin D and colorectal cancer no significant(P > 0.05).(2)The proximal colorectal cancer group and healthy control group plasma 25-Hydroxy Vitamin D levelsAs a result of univariable analysis,there was no significant difference between the two groups on plasma 25-Hydroxy Vitamin D levels(P=0.603).Multivariate results display that by control Variables like plasma sTNFR2,endotoxin,the dietary intake of fruits and vegetables,smoking and age factors,use the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)as compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / m L)and secondary plasma 25-Hydroxy Vitamin D students vitamin D levels(12.42-15.75ng/m L)relative risk(95% CI)were 1.09(0.48,2.48)and 0.73(0.30,1.76).The results showed that the plasma levels of 25-Hydroxy Vitamin D and proximal colorectal cancer is not significant(P > 0.05).(3)Distal colorectal cancer group and healthy control group plasma 25-Hydroxy Vitamin D levelsSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.170).Multivariate results display in control plasma sTNFR2,endotoxin,the dietary intake of fruits and vegetables,smoking and salting food and other factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / mL)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/mL relative dangerous degree(95% CI)were 1.14(0.48,2.88)and 0.62(0.23,1.66),showed that plasma 25-Hydroxy Vitamin D and distal colorectal cancer no significant(P > 0.05).2.The role of gut flora abundance index in the relationship between vitamin D and colorectal cancer(1)Flora abundance index Chao,vitamin D and colorectal cancera.Flora low abundance(Chao ≤306)colorectal cancer group and flora low abundance(Chao ≤306)healthy control group,the levels of 25-Hydroxy Vitamin D comparisonSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.214).Multivariate results display in control plasma sTNFR2,endotoxin,the dietary intake of fruits and vegetables,red meat intake and drinking tea factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / mL)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/m L relative risk(95% CI)were 2.32(0.74,7.28)and 0.62(0.19,204).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria group low abundance(Chao ≤306)of colorectal cancer without significant(P > 0.05).b.The high abundance(Chao>306)of the colorectal cancer group and the high abundance of bacteria group(Chao>306)in healthy control group plasma 25-Hydroxy Vitamin D comparisonSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.665).Multivariate results display in control plasma sTNFR2,endotoxin,the dietary intake of fruits and vegetables,tea drinking,smoking and age factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / mL)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/mL relative risk(95% CI)were 0.38(0.08,rectal cancer 1.75)and 0.88(0.20,3.90),indicating that plasma 25-Hydroxy Vitamin D and bacteria group high abundance Chao>306 no statistical association(P > 0.05).(2)Flora abundance index Ace,vitamin D and colorectal cancera.Flora low abundance(ACE ≤ 312)of colorectal cancer group and flora low abundance(ACE ≤ 312)healthy control group,the levels of 25-Hydroxy Vitamin D comparisonUnivariate analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D levels(P=0.223).Multivariate results display in control plasma sTNFR2,endotoxin,the dietary intake of fruits and vegetables,red meat intake and drinking tea factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75,)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/m L relative risk(95% CI)were 1.58(0.45,555)and 0.69(0.18,266).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria group low abundance(ACE ≤312)of colorectal cancer without significant(P > 0.05).b.Flora of high abundance(Ace>312)of the colorectal cancer group and the flora of high abundance(Ace>312)healthy control group,plasma 25-Hydroxy Vitamin DUnivariate analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D levels(P=0.423).Multivariate results display in control plasma sTNFR2,endotoxin,the dietary intake of fruits and vegetables,tea drinking,smoking and age factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / mL)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/m L relative risk(95% CI)were 0.43(0.12,1.53)and 0.76(0.22,269).In combination with the Chao index and Ace index,there was no correlation between the level of plasma 25-Hydroxy Vitamin D and the incidence of colorectal cancer,and the relationship was not affected by the abundance of bacteria.3.The role of intestinal flora diversity in the relationship between vitamin D and colorectal cancer(1)Bacterial diversity index Shannon,vitamin D and colorectal cancera.Flora low diversity(Shannon ≤3.17)colorectal cancer group and flora low diversity(Shannon ≤3.17)in healthy control group,the levels of 25-Hydroxy Vitamin D comparisonSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.622).Multivariate results display in control plasma sTNFR2,endotoxin,garlic,vegetable intake,eggs intake factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / m L)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/m L relative risk(95% CI)were 1.59(0.46,553)and 0.64(0.18,2.26).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria group low diversity(Shannon ≤3.17)colorectal cancer without significant(P > 0.05).b.The comparison of plasma 25-Hydroxy Vitamin D in the group of colorectal cancer with and high diversity(Shannon >3.17)in the healthy control groupSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.296).Multivariate results display in control plasma sTNFR2,endotoxin,garlic,vegetable intake,eggs intake factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / m L)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/m L relative risk(95% CI)were 0.39(0.09,1.75)and 0.85(0.20,3.70).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria group high diversity(Shannon >3.17)colorectal is not significant(P > 0.05).(2)Bacterial diversity index Simpson,vitamin D and colorectal cancera.The low diversity(simpson >0.089)of the colorectal cancer group and the low diversity(simpson >0.089)in the healthy control group plasma 25-Hydroxy Vitamin D comparisonSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.412).Multivariate results display in control plasma sTNFR2,endotoxin,garlic,eggs intake factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / mL)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/m L relative risk(95% CI)were 1.22(0.41,3.62)and 0.46(0.15,1.38).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria group low diversity(simpson>0.089)colorectal have no significant(P > 0.05).b.Flora of high diversity(Simpson ≤0.089)colorectal cancer group and flora high diversity(Simpson ≤0.089)in healthy control group,the levels of 25-Hydroxy Vitamin D comparisonSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.242).Multivariate results display in control plasma sTNFR2,endotoxin,garlic,vegetable intake,eggs intake factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / m L)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/mL relative risk(95% CI)were 0.65(0.16,2.70)and 1.60(0.37,692).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria populations of high diversity(Simpson ≤0.089)of colorectal cancer without significant(P > 0.05).According to the bacterial diversity index Simpson and Simpson,there was no correlation between the level of plasma 25-Hydroxy Vitamin D and the incidence of colorectal cancer,and the relationship between them was not affected by the diversity of the flora.4.The role of Alpha diversity in the relationship between vitamin D and colorectal cancer(1)Low Alpha diversity,vitamin D and colorectal cancer.a.The comparison of plasma 25-Hydroxy Vitamin D in the low Alpha group and the low Alpha diversity healthy control groupSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.280).Multivariate results display in control plasma sTNFR2,endotoxin,vegetable intake,intake of fruits,red meat intake factors,with the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / mL)and secondary plasma 25-Hydroxy Vitamin D students vitamin D levels(12.42-15.75ng/mL)relative risk(95% CI)were 1.11(0.31,4.04)and 0.46(0.11,1.94).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria group low alpha diversity of colorectal cancer without significant(P > 0.05).b.Low Alpha diversity and low expression of VDR receptor in colorectal cancer group and low Alpha diversity in healthy control group plasma 25-Hydroxy Vitamin D comparisonSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.405).Results showed that multiple factors in the control of plasma sTNFR2,endotoxin,vegetable intake,physical labor and other factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / m L)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / m L)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/m L relative risk(95% CI)were 0.85(0.60,6.35)and 1.94(0.25,2.89).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria group low alpha diversity and VDR low expression of colorectal cancer without significant(P > 0.05).c.The low Alpha diversity and VDR receptor expression in colorectal cancer group and the low Alpha diversity of healthy control group plasma 25-Hydroxy Vitamin D comparisonSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.196).Multivariate results display in control plasma sTNFR2,endotoxin,intake of fruits,pickled food intake factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / m L)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/m L relative risk(95% CI)were respectively 1.64(0.11,3.77)and 0.63(0.21,12.73).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria group low alpha diversity and VDR expression of colorectal cancer without significant(P > 0.05).(2)High Alpha diversity,vitamin D and colorectal cancer.a.The comparison of plasma 25-Hydroxy Vitamin D in the high Alpha group and the high Alpha diversity healthy control groupSingle factor analysis showed that there was no significant difference between in the two groups on plasma 25-Hydroxy Vitamin D(P=0.766).Multivariate results display in control plasma sTNFR2,endotoxin,vegetable intake,intake of fruits,red meat intake factors,with the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / m L)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / mL)and secondary plasma 25-Hydroxy Vitamin D students vitamin D levels(12.42-15.75ng/m L)relative risk(95% CI)were 1.74(0.69,4.41)and 0.76(0.29,1.96).The results showed that the plasma levels of 25-Hydroxy Vitamin D and bacteria group high alpha diversity of colorectal cancer without significant(P > 0.05).b.The high Alpha diversity and low expression of VDR receptor in colorectal cancer group and the high Alpha diversity of the healthy control group plasma 25-Hydroxy Vitamin D comparisonSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.977).Due to the results of univariate p value is too high,multi factor regression does not change the correlation and plasma 25-Hydroxy Vitamin D and bacteria group high alpha diversity and VDR low expression of colorectal cancer no statistical association(P > 0.05).c.The high Alpha diversity and VDR receptor expression in colorectal cancer group and the high Alpha diversity of healthy control group plasma 25-Hydroxy Vitamin D comparisonSingle factor analysis showed that there was no significant difference between the two groups of plasma 25-Hydroxy Vitamin D(P=0.536).Multivariate results display in control plasma sTNFR2,endotoxin,intake of fruits,pickled food intake factors,and the lowest level of plasma 25-Hydroxy Vitamin D levels(less than or equal to 12.42 ng / mL)compared to the high plasma 25-Hydroxy Vitamin D levels(> 15.75 ng / m L)and secondary plasma 25-Hydroxy Vitamin D levels 12.42-15.75ng/mL relative risk(95% CI)were 2.75(0.44,17.30)and 193(0.13,29.10),indicating that plasma 25-Hydroxy Vitamin D and bacteria group high alpha diversity and VDR receptors are highly expressed in colorectal cancer without significant(P > 0.05).To sum up,there is no correlation between the level of plasma 25-Hydroxy Vitamin D and the incidence of colorectal cancer.The relationship is not affected by the diversity of Alpha and the expression of vitamin D receptor.Conclusion:The study find that the correlation between plasma 25-Hydroxy Vitamin D and colorectal cancer is of no statistical significance which is not affected by the location of colorectal cancer,the diversity of intestinal flora and the expression of vitamin D receptor.