Characterization Of Gut Microbiome In Patients With HIV Associated Neurocognitive Disorder

Objectives: Nowadays,most HIV infected people have achieved virological inhibition.However,HIV associated neurocognitive disorder(HAND)is still plagues them.Previous researches indicated that gut microbiome may play a role in the pathogenesis of HAND in HIV-infected patients,but the results of studies on the characteristics of gut microbiome in HAND patients are heterogeneous,and previous studies have not explored the role of cytokines in HAND.Therefore,this study explored the internal relationship between gut microbiome and HAND by analyzing the composition of gut microbiome and the levels of inflammatory factors in plasma of patients with HAND.Methods: This study took Center for AIDS treatment of Anhui Province as the research site.HIV-positive patients attending immunization clinics were recruited between November 2021 and March 2022.A questionnaire was used to collect information on the general demographic characteristics and sexual behavior characteristics of the participants.Blood samples and stool samples were also collected for Luminex multifactor testing and 16 S r DNA amplicon sequencing.Propensity score matching(PSM)was used to control for confounding factors between the two groups.HAND diagnostic biomarkers were screened by random forest model.Results:(1)A total of 86 study subjects were included in this study,including 32 cases in the HAND group and 54 cases in the non-HAND group.After matching,there were 32 study subjects in each of the two groups.Among them,the mean age age of the HAND group was(47.72±10.18)years,and 46.9% had a bachelor’s degree or higher in education;the age of the non-HAND group was(44.47±8.84)years,and 40.6% had a bachelor’s degree or higher in education.(2)There was no statistically significant difference in α diversity between the HAND and no-HAND groups before matching(P>0.05),while there was a significant difference in both α and β diversity between the two groups after matching(P<0.05).Also,the results of LEfse analysis showed that there were significant differences in gut microbiome composition between the two groups after matching.At the class level,the relative abundance of Clostridia in the HAND group was higher than that of the non-HAND group(LDA=4.805,P=0.002),while the relative abundance of Negativicutes was lower than that of the non-HAND group(LDA=4.810,P=0.035).At the order level,the relative abundance of Clostridiales in the HAND group was higher than that in the nonHAND group(LDA=4.805,P=0.002),while the relative abundance of Selenomonadales in the HAND group was lower than that in the non-HAND group(LDA=4.810,P=0.035).At the family level,the relative abundance of Lachnospiraceae(LDA=4.544,P=0.002)and Bacteroidaceae(LDA=4.858,P=0.029)was higher in the HAND group,while the relative abundance of Prevotellaceae(LDA=4.883,P=0.030)was lower in the HAND group.At the genus level,the relative abundance of several HAND genera was high,including Bacteroides(LDA=4.858,P=0.029),Clostridium_IV(LDA=2.925,P=0.011),and Ruminococcus(LDA=3.430,P=0.005),while Prevotella(LDA=4.867,P=0.035)and Acidaminococcus(LDA=4.077,P=0.001)were lower in relative abundance.(3)Metabolic pathways such as lipid metabolism(5.54% vs 4.78%,P<0.001)and signaling(0.35% vs 0.29%,P=0.010)were higher in the HAND group,while metabolic pathways such as cofactor and vitamin metabolism(13.23% vs 13.94%,P=0.013),amino acid metabolism(12.73% vs 12.98%,P=0.028),cell growth and death(1.59% vs 1.70,P=0.014)were lower.(4)Seven genus were screened as the optimal diagnostic biomarkers for HAND by random forest model,and the area under the ROC curve was 67.68%(95% CI:41.25%-94.10%).(5)There were no significant differences in the levels of various cytokines,such as microbial translocation markers and inflammatory factors,between the HAND and non-HAND groups.The correlation results of gut microbiome and cytokines between groups showed that there was a negative correlation between BDNF and Clostridium XVIII(rs =-0.351,P=0.004)and a positive correlation between BDNF and Acidaminococcus(rs = 0.303,P=0.015);a negative correlation between s CD14 and Prevotella(rs=-0.283,P=0.023);a positive correlation between CRP and Acidaminococcus(rs=0.323,P=0.009);a positive correlation between CD106 and Eggerthella(rs=0.259,P=0.038).Conclusions:(1)There are differences in alpha and beta diversity between HAND patients and normal cognitively HIV-infected patients.Compositionally,the gut microbiome of HAND patients also differs significantly from that of normal cognitively HIV-infected patients.(2)There is some correlation between gut microbiome and cytokines,and cytokines may play a role in the pathogenesis of HAND due to gut microbiome.(3)The gut microbiome gene function is altered in HAND patients,mainly in the metabolic pathways related to lipid metabolism,amino acid metabolism,cofactors,and vitamin metabolism.(4)The results of the random forest model suggest that gut microbiome has exploratory value in the diagnosis of HAND,which may be used as a reference for clinical diagnosis in the future.