Association Between Short-Chain Fatty Acids-Producing Bacterial Diet And Dyslipidemia

Objective:Dyslipidemia is a clear risk factor for cardiovascular disease.Previous studies suggest that dietary fiber is dependent on specific intestinal bacteria to produce short-chain fatty acids（SCFAs）;while high-fiber diet and its metabolite SCFAs can improve blood lipid profile;on the other hand,diet can module the structure and function of intestinal bacteria.Therefore,we hypothesized that diet could reduce the risk of dyslipidemia through specific intestinal bacteria and their dependent metabolite SCFAs.The aim of present study was to derive and validate a SCFAs-producing bacterial diet（SPBD）pattern based on intestinal bacteria associated with the production of SCFAs.The associations between SPBD adherence-score and dyslipidemia（including subtypes）and lipid levels were also assessed in a community-based cross-sectional study in Lu’an.Methods:This study was a community-based cross-sectional study in Lu’an,Anhui.Multi-stage sampling was used for the selection of the participants.Food frequency questionnaire（FFQ）was used to investigate the frequency and consumption of each food in the past year.In this cross-sectional study（n=2679）,individuals who provided eligible fecal specimens in Huoshan were selected as the population to derive SPBD（n=392）.16S r RNA gene sequencing was used to analyze the classification and composition of fecal bacteria.The population deriving SPBD was randomly divided into a construction set（n=270）and a validation set（n=122）according to the proportion of 2:1.In the construction set,the SPBD was derived based on reduced rank regression using 41 foods or food groups as predictor variables and the relative abundance of SCFAs（propionic acid and butyric acid）-associated bacteria（Phascolarctobacterium succinatutens,Bacteroides,Veillonella,Dialister,Megasphaera elsdenii,Coprococcus catus,Roseburia inulinivorans,Coprococcus eutactus,Anaerostipes,Faecalibacterium prausnitzii）as response variables.In the validation set,the ability of SPBD-adherence score to predict the relative abundance of 10 intestinal bacteria was evaluated by multiple linear regression.Dyslipidemia,high total cholesterol（TC）,high triglyceride（TG）,high low-density lipoprotein cholesterol（LDL-C）,and low high-density lipoprotein cholesterol（HDL-C）were defined according to the guidelines for the prevention and treatment of dyslipidemia in Chinese adults（2016 revision）.We then applied the SPBD-adherence score into the total Lu’an population.Multivariate logistic regression was used to estimate the odds ratios（ORs）and 95%confidence intervals（CIs）for the associations of SPBD-adherence score with dyslipidemia and its subtypes.Linear regression was used to assess the associations between SPBD and the relative concentrations of the four blood lipid items（continuous variables）.We also used restricted cubic spline to identify the dose-response relationship between SPBD-adherence score and dyslipidemia.In the sensitivity analyses,considering the influence of recall bias on the analysis results,participants whose dietary habits had changed in the past five years were excluded for analysis.To reduce the measurement error and reflect dietary composition,we adjusted the SPBD-adherence score for total energy intake using the nutrient residual method.Results:A total of 2679 participants were included in present study,including 842 with dyslipidemia,138 with high TC,411 with high TG,491 with low HDL-C and 129 with high LDL-C.In the construction set,SPBD included 15 foods or food groups,in which mushroom,tea,soy beverages,soy products,other vegetables and other aquatic products were positively associated with the abundance of SCFAs-producing bacteria.While pickled vegetables,red meat,animal organ,shrimps,eggs,liquor,condiments,barbecued food and sugar-sweetened beverage were negatively associated with the abundance of SCFAs-producing bacteria.In the validation set,compared with those in the lowest quintile of SPBD-adherence score,participants in the highest quintile had a higher relative abundance of SCFAs-producing bacteria,with the percentage change of 96.9%(95%CI:39.1%～178.7%,P _trend<0.001)in the overall relative abundance of the 10SCFAs-producing bacteria,which could effectively predict the overall abundance of the10 SCFAs-producing bacteria.Multivariate logistic regression showed that after adjusting for age,sex and other covariates,compared with the lowest quintile of SPBD-adherence score,the odds for the dyslipidemia in the highest quintile was 0.71(OR=0.71,95%CI:0.54-0.93,P _trend=0.021).Such positive association persisted after further excluding individuals whose dietary habits had changed in the past five years as well as using the nutrient residual method to adjust the SPBD-adherence score.Restricted cubic spline analysis did not support the non-linear association between SPBD-adherence score and odds of dyslipidemia(P _nonlinearity=0.057).Additionally,higher SPBD-adherence score was associated with 32%lower odds of high TG(OR=0.68,95%CI:0.48-0.95,P _trend=0.044).We did not find any significant association between SPBD-adherence score and odds of high TC,low HDL-C,and high LDL-C.Similarly,linear regression showed that SPBD-adherence score was negatively associated with TG levels,with the percentage difference of-6.9%(95%CI:-13.3%～-0.1%,P _trend=0.047)in participants with the highest quintile of SPBD-adherence score,compared to those with the lowest quintile.We found a non-significant association of SPBD-adherence score with TC,HDL-C and LDL-C.Conclusion:The SPBD derived based on reduced rank regression can well predict the relative abundance of SCFAs-producing bacteria.Adherence to SPBD was inversely associated with the prevalence of overall dyslipidemia and high TG.Our findings suggest at the population level that adherence to SPBD can reduce the risk of dyslipidemia through specific intestinal bacteria and its dependent metabolite SCFAs,which has a certain application significance,and provides the mechanism value of some intestinal bacteria in reducing hyperlipidemia.Since this study is based on a cross-sectional design,further prospective studies are warranted to confirm our findings.