The Association Between Lifestyle Factors And Chronic Inflammatory Cytokines In Helicobacter Pylori Infected Patients

Background and aims:Helicobacter pylori（HP）is an independent risk factor for gastric mucosal damage,gastritis,ulcer,and cancer.It causes gastric lesions by interacting with host cells within the gastric mucosa and activating various innate immune signalling pathways,leading to the producing pro-inflammatory cytokines and recruiting.Lifestyle factors have been found to play a positive role in reducing inflammation and preventing various cancers and gastric diseases,but few studies have tested the association between different lifestyle factors and inflammatory cytokines in HP-infected patients.Therefore,this study aims to investigate the correlation between lifestyle factors and the levels of various inflammatory cytokines in HP-infected patients,which will provide population-based data for the development of early preventive measures for diseases caused by HP infection.Methods:This study recruited participants from two hospitals in Baiyin City,Gansu Province.According to the inclusion and exclusion criteria,179 subjects were finally enrolled based on the results of the ¹⁴C breath test and ¹³C breath re-test.Demographic information and lifestyle information（including smoking,alcohol consumption,daily activities,sleep and eating behaviour）were collected at baseline and follow-up（2 months interval）by the questionnaire method and physical examination（height,weight,and BMI）.Combined adverse lifestyle score was calculated based on the above-mentioned information.Fasting venous blood was collected from the study subjects to examine the levels of seven inflammatory cytokines（including TNF-α,IL-1β,IL-17A,CRP,IL-8,IL-18,IFN-γ）and pepsinogen（PGⅠ,PGⅡ）.Firstly,the relationship between each lifestyle component and the combined adverse lifestyle score and inflammatory cytokines at baseline was analysed by multiple linear regression,and then the relationship between the continuous variable components of combined adverse lifestyle and inflammatory cytokines was analysed by fitting smoothed curves and segmented regression to explore the threshold or saturation effects of different lifestyles and inflammatory cytokines.The relationship between the changed of each lifestyle factor and combined adverse lifestyle score and the difference of inflammatory cytokines values over 2 months were subsequently analysed by multiple linear regression,while restrictive cubic spline function plots were drawn to explore the dose-response relationship between lifestyle factors change and inflammatory cytokines change.stratification analysis was then performed according to different level of ¹³C-UBT test DOB values.In addition,a weighted combined adverse lifestyle score was calculated based on the standardisedβof the different lifestyles and a combined adverse lifestyle score was calculated by sequentially excluding the combined adverse lifestyle component and excluding patients with possible atrophic gastritis for sensitivity analysis.Results:At baseline,the highest number of people with a combined adverse lifestyle score of 2（8 points in total）was 42（23.46%）,followed by those with a score of 3,39（21.79%）.By the 2-month follow up 50（27.93%）had not changed their combined adverse lifestyle score,54（30.17%）had increased their score and 75（42.00%）had decreased their score.At baseline,IFN-γlevels increased by 1.33（95%CI:0.02,2.64）pg/m L for every1-point increase in the combined adverse lifestyle score,and no correlation was found with other inflammatory cytokines.In the combined adverse lifestyle components,alcohol consumption was found to be associated with elevated IFN-γ（β=5.58,95%CI:0.61 to 10.55）;BMI levels were associated with elevated LNCRP（β=0.04,95%CI:0.01 to 0.06）and an increase in BMI above 27.07 kg/m² was associated with elevated IL-1β（β=0.61.95%CI:0.01 to 1.21）;Decreased daily activity was associated with increased TNF-αlevels（β=1.01,95%CI:0.00 to 2.03）and with increased IL-8levels（β=5.16,95%CI:0.64 to 9.76）;Increased sleep duration was linearly associated with increased IL-1βlevels（β=0.74,95%CI:0.06 to 1.42）,and when sleep duration exceeded 8.75 hours,the increase in sleep duration was accompanied by an increase in TNF-α（β=6.04;95%CI:1.18 to 10.89）and an increase in IL-18 levels（β=17.25,95%CI:0.26 to 34.25）when sleep duration exceeded 7.97 hours.No correlation was found between eating behaviour scores and each inflammatory cytokine.Up to the 2-month follow-up,for every 1 point increase in the value of change in the combined adverse lifestyle score,there appeared to be a correlated increase of 0.71（95%CI:0.01,1.41）pg/m L in TNF-α,1.16（95%CI:0.36,1.96）pg/m L in IL-17A,and1.97（95%CI:0.48,3.46）pg/m L in IFN-γ,where the increase in combined adverse lifestyle score showed a linear dose-response relationship with the increase in IL-17A（P=0.022,P for nonlinear=0.758）and IFN-γ（P=0.029,P for nonlinear=0.543）levels.An increase in the change of daily activity score was associated with an increase in IL-17A（β=1.55,95%CI:0.36 to 2.74）and an increase in IFN-γ（β=2.50,95%CI:0.10 to 4.90）;Fitting restricted cubic spline plots also revealed a linear dose-response between a decrease in daily activity and an increase in IL-17A and IFN-γ（P=0.003,P for nonlinear=0.221;P=0.033,P for nonlinear=0.851）;There was a positive linear dose-response relationship between sleep duration and IFN-γ（P=0.049,P for nonlinear=0.472）;Increasing adverse eating behaviour scores were positively associated with increasing IFN-γ（β=2.40,95%CI:0.09 to 4.71）.Further subgroup analysis revealed that the relationship between the mentioned lifestyle factors and inflammatory cytokines was only observed in the patients with high DOB values.Sensitivity analysis revealed that the physical activity component of the combined adverse lifestyle factors was the main factor associated with IL-17A and IFN-γ,and the sleep component was the main factor associated with TNF-α.The results of the analysis were similar to those of the whole sample after excluding subjects with possible atrophic gastritis.Conclusions:（1）Increases in the combined adverse lifestyle score were associated with increased levels of TNF-α,IL-17A and IFN-γand the strength of the association was higher in subjects with higher DOB values,with daily activity playing a significant contribution to the association of the combined adverse lifestyle score with IL-17A and IFN-γand sleep playing a significant contribution to the association with TNF-α.（2）Changes in each component of the composite poor lifestyle were associated with changes in TNF-α,IL-17A,CRP,IL-8,IL-18,and IFN-γ.（3）A 2-month improvement in lifestyle may lower TNF-α,IL-17A,and IFN-γlevels in participants in the study.