Recurrent gastric carcinoma treated by the Geiger probe technique.

Abstract

<h3>Abstract</h3> Multiomics technologies improve the biological understanding of health status in people living with HIV on antiretroviral therapy (PLWH_ART). Still, a systematic and in-depth characterization of metabolic risk profile during successful long-term treatment is lacking. Here, we used multi-omics (plasma lipidomic and metabolomic, and fecal 16s microbiome) data-driven stratification and characterization to identify the metabolic at-risk profile within PLWH_ART. Through network analysis and similarity network fusion (SNF), we identified three groups of PLWH_ART (SNF-1 to 3). The PLWH_ART at SNF-2 (45%) was a severe at-risk metabolic profile with increased visceral adipose tissue, BMI, higher incidence of metabolic syndrome (MetS), and increased di- and triglycerides despite having higher CD4⁺ T-cell counts than the other two clusters. However, the healthy-like and severe at-risk group had a similar metabolic profile differing from HC, with dysregulation of amino acid metabolism. At the microbiome profile, the healthy-like group had a lower α-diversity, a lower proportion of MSM, and was enriched in Bacteroides. In contrast, in at-risk groups, there was an increase in <i>Prevotella</i>, with a high proportion of men who have sex with men (MSM) confirming the influence of sexual orientation on the microbiome profile The multi-omics integrative analysis reveals a complex microbial interplay by microbiome-derived metabolites in PLWH_ART. PLWH_ART those are severely at-risk clusters may benefit from personalized medicine and lifestyle intervention to improve their metabolic profile. <h3>Significance</h3> The network and factorization-based integrative analysis of plasma metabolomics, lipidomics, and microbiome profile identified three different diseases’ state -omics phenotypes within PLWH_ART driven by metabolomics, lipidomics, and microbiome that a single omics or clinical feature could not explain. The severe at-risk group has a dysregulated metabolic profile that potentiates metabolic diseases that could be barriers to healthy aging. The at-risk group may benefit from personalized medicine and lifestyle intervention to improve their metabolic profile.