Meta-analysis Of Intestinal Differential Bacteria In Alzheimer’s Disease Based On 16SrRNA Gene Sequencing

Objective: At present,comparative studies on intestinal flora differences between patients with Alzheimer’s disease(AD)and healthy controls by sequencing 16 s ribosomal RNA(16Sr RNA)genes in faecal samples are being carried out gradually.However,the specific trend of different intestinal bacteria genera and their abundances are controversial.The purpose of this study is to synthesize the results of relevant studies statistically and quantitatively,to explore the intestinal differential bacteria between AD patients and healthy control groups,namely the possible potential intestinal biomarkers of AD,to provide ideas for the diagnosis of AD biomarkers,and to provide new targets for the prevention and treatment of AD.Methods: Through comprehensive and in-depth inquiry of China National Knowledge Network,Wanfang database,VIP database,China Biomedical literature database,Pub Med,Web of Science,the Cochrane Library,Embase database,and conduct a manual search to discover and access all relevant research as of January 2023.The inclusion and exclusion criteria were strictly formulated,and the research was screened and information extracted by two people independently.The Cochrane bias risk assessment method and Newcastle-Ottawa Quality Assessment Scale(NOS)were used to assess the risk of bias.The stata14 software was used to synthesize and analyze the literatures that met the quality requirements.Standardized mean difference(SMD)was used as the effect index.Point estimates and 95%confidence interval(95% CI)were given for each effect size.I2 statistic and Chi-square test were combined to evaluate the heterogeneity of the results,and I2≥ 50% indicated significant heterogeneity.Random effects model was used to adjust the heterogeneity,and subgroup analysis and sensitivity analysis were conducted if necessary to explore the source of heterogeneity.Publication bias was evaluated by funnel plot and Begg test.The test level was α=0.05.Results: A total of 1566 relevant literatures were obtained in this study,and 13 original literatures were finally included.It was found that Akkermansia,Ruminococcus,Phascolarctobacterium,Faecalibacterium,Lachnospira,Dialister,Lactobacillus,Lachnoclost ridium,and Roseburia were different intestinal bacteria between AD patients and healthy control group,among which Ruminococcus [SMD=-0.48,95%CI(-0.76 ～-0.22),I2 =0 %],,Faecalibacterium [SMD=-0.62,95%CI(-0.82 ～-0.43),I2 = 21.7 %],Lachnospira SMD=-0.42,95%CI(-0.71 ～-0.13,I2 =25.1%),Dialister [SMD=-2.32,95% CI(-2.66 ～-1.97),I2 = 35%],Lachnoclostridium [SMD=-0.36,95% CI(-0.68 ～-0.04),I2 =10.2%],Roseburia [SMD=-0.71,95%CI(-1.28 ～-0.15),I2 =64%] were lower in AD patients than in healthy controls,and Akkermansia [SMD=0.46,95%CI(0.24-0.68),I2 =0%],Phascolarctobacterium,[SMD=1.65,95%CI(1.09-2.22),I2=0%],Lactobacillus[SMD=0.41,95% CI(0.13-0.69),I2 =0%] was higher in AD patients than in healthy controls.Subgroup analysis showed that bacterial abundance of Bacteroides in AD patients in Egypt and the United States was higher than that in healthy control group[SMD=0.79,95%CI(0.29-1.28),I2 =58%],and bacterial abundance of bifidobacterium in AD patients in China was higher than that in healthy control group [SMD = 0.47,95%CI(0.23 ～ 0.70),I2 =19%],the abundance of Alistipes in AD patients in the United States was higher than that in the healthy control group [SMD=0.49,95%CI(0.12 ～0.33),I2 =0%],while the abundance in AD patients in China was lower than that in the healthy control group [SMD=-0.78,95%CI(-1.28 ～-0.29),I2 =69.2%].Conclusion:Akkermansia,Ruminococcus,Phascolarctobacterium,Lachnoclostridium,Fae calibacterium,Lachnospira,Lactobacillus,Dialister and Roseburia are different intestinal bacteria between AD patients and healthy control groups,and are possible potential intestinal biomarkers for AD.Bacteroides was found to be more abundant in AD patients in Egypt and the United States than in the healthy control group,bifidobacterium was found to be more abundant in AD patients in China than in the healthy control group,and Alistipes was found to be more abundant in AD patients in the United States than in the healthy control group,but the abundance in AD patients in China was lower.In future studies,larger scale and higher quality multi-center case-control studies and longitudinal studies are needed to further validate the findings of this study.