Sex specific gut bacterial community structure: implications for frailty risk in people with HIV

Frailty is a major health concern associated with aging and has been linked to gut microbiome composition, especially in elderly individuals needing care. People with HIV (PWH) present high risk of early-onset frailty. This study examines the relationship between frailty and the gut microbiome, with an emphasis on sex-based differences in PWH. Data were drawn from 268 participants in the New Orleans Alcohol Use in HIV (NOAH) Study, including 16S microbiome sequencing from stool samples, cytokine levels, viral load, and T cell counts. Frailty was assessed using phenotypic frailty index (PFI) and a 58-item deficit index (DI-58). Fourteen taxa were significantly linked to both PFI and DI-58. Among females, butyrate-producing genera (e.g., Eubacterium ventriosum and Butyricimonas) were inversely associated with frailty, while genera such as Paraprevotella and Romboutsia showed positive associations. In males, Prevotella and Erysipelotrichaceae UCG-003 were inversely associated, whereas Christensenellaceae R-7, Clostridium sensu stricto, and others were positively associated with frailty. Fifteen genera were also linked to circulating cytokine levels (IL-1β, IL-17A, IL-2, IFN-γ). We identified three community state types (CSTs) with unique bacterial structures. Community state analysis identified CST 2, characterized by lower diversity and more pathobionts, to be highly predictive of increased frailty. These findings underscore the relevance of sex-specific differences in the gut microbiota relations with frailty, supporting tailored interventions for frailty in PWH.