Integration of genome-wide association studies (GWAS) and microbiome data highlights the impact of sulfate-reducing bacteria on Alzheimer’s disease

Abstract

Abstract Background observational studies have indicated that gut microbiome dysbiosis was associated with Alzheimer’s disease (ad). However, the results are largely inconsistent and it remains unknown whether the association is causal in nature. Methods leveraging observational studies and genome-wide association studies (GWAS) on the gut microbiome in ad patients, we pooled the microbiome data (N = 1,109) to screen the microbiota significantly altered in ad patients and then conducted Mendelian randomisation (MR) study to determine the causal associations between altered microbiota (N = 18,340) and ad using two different ad GWAS datasets (N = 63,926 and N = 472,868) using the inverse variance-weighted (IVW) method. Results the combined effect sizes from observational studies showed that 8 phyla, 18 classes, 22 orders, 37 families, 78 genera and 109 species significantly changed in ad patients. Using the MR analysis, we found that two classes, one order, one family and one genus were suggestively associated with ad consistently in two different GWAS datasets. Both observational studies and MR analysis simultaneously showed that Desulfovibrionales (order) and Desulfovibrionaceae (family), which were mainly implicated in dissimilatory sulfate reduction, were significantly associated with an elevated risk of ad. Conclusions our findings demonstrated that the abundance of sulfate-reducing bacteria was increased in ad patients, which was causally linked to an increased risk of ad. Further efforts are warranted to clarify the underlying mechanisms, which will provide new insight into the prevention and treatment of ad.