Frailty Is Associated With Changes In Gut Bacterial Absundance In People Living With HIV

Document Type

Article

Publication Date

8-14-2024

Publication Title

Drug and Alcohol Dependence

Abstract

Background: Combination antiretroviral therapy (cART) has prolonged the lifespan of people with HIV (PWH); however, it does not completely restore the composition of intestinal microbiota to that of an HIV-negative microbiome. HIV infection, despite effective cART, is also associated with an earlier onset of geriatric comorbidities, contributing to increased risk for poor HIV-related outcomes. Frailty is defined as the increased vulnerability for age-associated health decline, and frail people are prone to polypharmacy, multi-morbidity, and ART low adherence. We hypothesize that frailty is correlated with gut microbiome changes in PWH. Methods: Data and samples were obtained from 268 participants enrolled in the New Orleans Alcohol Use in HIV (NOAH) Study. Fecal samples were used to perform deep sequencing was performed on the Illumina MiSeq V2 platform. Frailty was estimated by the Phenotypic Frailty Index (PFI) and the Deficit Index-58 items (DI58). The statistical analyses were performed using either SAS or R. Results: 80 females (Mean age +/-SD = 47 +/- 10 years) and 188 males (age 49 +/- 10 years) were enrolled. The DI58 median score was not statistically significant between females and males (10.20, 8.8, respectively, p= 0.0507). The PFI was stratified by the score obtained for each participant on a 5-point scale, where 0 = non-frail, 1-2 = pre-frail, and?>3 = frail. The classification for females as non-frail was 10.39%, pre-frail was 77.92% and frail was 11.68%; for males 22.34% were non-frail, 70.39% were pre-frail, and 7.26% were categorized as frail. There were no significant differences between males and females for each category. The bacteria relative abundance was converted to centered log-ratio for further analysis. Linear regression was performed to verify the relationship between frailty and gut microbiome. DI58 was found to be positively correlated with Escherichia-Shigella (ℬ= 0.237, SE= 0.09, p=0,009) and Clostridium sensu (ℬ= 0.337, SE= 0.144, p=0.02). While PFI was positively associated with increased abun-dance of Anaerotruncus (ℬ= 0.067, SE= 0.029, p=0.022) and negatively associated with Allisonella (ℬ= -0.055, SE= 0.023, p=0.017), Suterella (ℬ=-0.045, SE= 0.021, p=0.033), Lachnos-piraceae UCG 004 (ℬ= -0.064, SE= 0.027, p=0.019), and Family XIII UCG 001 genus (ℬ= -0.073, SE= 0.03, p=0.016). Conclusion: we have identified associations between frailty and the bacteria abundance of specific genera in the gut. Most impor-tantly, Escherichia/Shigella genus were previously shown to be associated with increased expression of pro-inflammatory cytokines as well as identified as the most abundant genera in critically ill older patients (>60 years). These data will guide further analysis to examine specific interactions between these genera and global inflammation in our NOAH Study cohort.

Volume

261

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