Disrupted microbial cross-feeding and altered L-phenylalanine consumption in people living with HIV

This work aims to (1) identify microbial and metabolic alterations and (2) reveal a shift in phenylalanine production-consumption equilibrium in individuals with HIV. We conducted extensive searches in multiple databases [MEDLINE, Web of Science (including Cell Press, Oxford, HighWire, Science Direct, IOS Press, Springer Nature, PNAS, and Wiley), Google Scholar, and Embase] and selected two case-control 16S data sets (GenBank IDs: SRP039076 and EBI ID: ERP003611) for analysis. We assessed alpha and beta diversity, performed univariate tests on genus-level relative abundances, and identified significant microbiome features using random forest. We also utilized the MICOM model to simulate growth and metabolic exchanges within the microbiome, focusing on the Metabolite Exchange Score (MES) to determine key metabolic interactions. We found that L-phenylalanine had a higher MES in HIV-uninfected individuals compared with their infected counterparts. The flux of L-phenylalanine consumption was significantly lower in HIV-infected individuals compared with healthy controls, correlating with a decreased number of consuming species in the chronic HIV stage. Prevotella, Roseburia, and Catenibacterium were demonstrated as the most important microbial species involving an increase in L-phenylalanine production in HIV patients, whereas Bacteroides, Faecalibacterium, and Blautia contributed to a decrease in L-phenylalanine consumption. We also found significant alterations in both microbial diversity and metabolic exchanges in people living with HIV. Our findings shed light on why HIV-1 patients have elevated levels of phenylalanine. The impact on essential amino acids like L-phenylalanine underscores the effect of HIV on gut microbiome dynamics. Targeting the restoration of these interactions presents a potential therapeutic avenue for managing HIV-related dysbiosis.