Comprehensive metabolomics profiling reveals common metabolic alterations underlying the four major non-communicable diseases in treated HIV infection

摘要

Background HIV infection and normal aging share immune and inflammatory changes that result in premature aging and non-communicable diseases (NCDs), but the exact pathophysiology is not yet uncovered. We identified the common metabolic pathways underlying various NCDs in treated HIV infection. Methods We performed untargeted metabolomics including 87 HIV-negative (–) normal controls (NCs), 87 HIV-positive ( ) NCs, and 148 HIV subjects with only one type of NCDs, namely, subclinical carotid atherosclerosis, neurocognitive impairment (NCI), liver fibrosis (LF) and renal impairment. All HIV subjects were virally suppressed. Results HIV patients presented widespread alterations in cellular metabolism compared to HIV– NCs. Glycerophospholipid (GPL) metabolism was the only one disturbed pathway presented in comparisons including HIV– NCs across age groups, HIV NCs across age groups, HIV NCs vs HIV– NCs and each of HIV NCDs vs HIV NCs. D-glutamine and D-glutamate metabolism and alanine-aspartate-glutamate metabolism were presented in comparisons between HIV NCs vs HIV– NCs, HIV LF or HIV NCI vs HIV NCs. Consistently, subsequent analysis identified a metabolomic fingerprint specific for HIV NCDs, containing 42 metabolites whose relative abundance showed either an upward (mainly GPL-derived lipid mediators) or a downward trend (mainly plasmalogen phosphatidylcholines, plasmalogen phosphatidylethanolamines, and glutamine) from HIV– NCs to HIV NCs and then HIV NCDs, reflecting a trend of increased oxidative stress. Interpretation GPL metabolism emerges as the common metabolic disturbance linking HIV to NCDs, followed by glutamine and glutamate metabolism. Together, our data point to the aforementioned metabolisms and related metabolites as potential key targets in studying pathophysiology of NCDs in HIV infection and developing therapeutic interventions. Funding China National Science and Technology Major Projects on Infectious Diseases, National Natural Science Foundation of China, Yi-wu Institute of Fudan University, and Shanghai Municipal Health and Family Planning Commission.