Diet Quality and Liver Health in People Living with HIV in the MASH Cohort: A Multi-Omic Analysis of the Fecal Microbiome and Metabolome

Abstract

The gut–liver axis has been recognized as a potential pathway in which dietary factors may contribute to liver disease in people living with HIV (PLWH). The objective of this study was to explore associations between dietary quality, the fecal microbiome, the metabolome, and liver health in PLWH from the Miami Adult Studies on HIV (MASH) cohort. We performed a cross-sectional analysis of 50 PLWH from the MASH cohort and utilized the USDA Healthy Eating Index (HEI)–2015 to measure diet quality. A Fibrosis-4 Index (FIB-4) score < 1.45 was used as a strong indication that advanced liver fibrosis was not present. Stool samples and fasting blood plasma samples were collected. Bacterial composition was characterized using 16S rRNA sequencing. Metabolomics in plasma were determined using gas and liquid chromatography/mass spectrometry. Statistical analyses included biomarker identification using linear discriminant analysis effect size. Compared to participants with FIB-4 ≥ 1.45, participants with FIB-4 < 1.45 had higher intake of dairy (p = 0.006). Fibrosis-4 Index score was inversely correlated with seafood and plant protein HEI component score (r = −0.320, p = 0.022). The relative abundances of butyrate-producing taxa Ruminococcaceae, Roseburia, and Lachnospiraceae were higher in participants with FIB-4 < 1.45. Participants with FIB-4 < 1.45 also had higher levels of caffeine (p = 0.045) and related metabolites such as trigonelline (p = 0.008) and 1-methylurate (p = 0.023). Dietary components appear to be associated with the fecal microbiome and metabolome, and liver health in PLWH. Future studies should investigate whether targeting specific dietary components may reduce liver-related morbidity and mortality in PLWH.

The Dose–Response Effect of Fluoride Exposure on the Gut Microbiome and Its Functional Pathways in Rats

“…Elevated blood urea nitrogen levels in children with idiopathic nephrotic syndrome positively correlate with the Ruminococcaceae genus [47]. Moreover, patients with conditions such as diabetic nephropathy [38], liver-kidney transplantation [48], hepatitis C virus (HCV) infection [49], non-alcoholic fatty liver [50], liver fibrosis [51], polycystic ovary syndrome [52], thyroid cancer [53], Parkinson's disease [54], autism spectrum disorder [55], multiple sclerosis [56], and spinal cord injury [57] all show a significant rise in the relative abundance of the Ruminococcaceae genus. After exposure to perfluorooctanesulfonic acid, there was a trend of increased abundance of Ruminococcaceae, but only the high-dose group was significantly higher than the control group [58].…”

HIV-1–Host Interaction in Gut-Associated Lymphoid Tissue (GALT): Effects on Local Environment and Comorbidities

“…In the context of non-AIDS-related comorbidities, the gut-liver axis has emerged as a potential pathway contributing to liver disease in PLWH. Microbes and their metabolites, after crossing the epithelial barrier, travel to the liver, passing through the portal circulation, and upregulate the inflammatory and fibrotic pathways [125,130]. Hepatic damage occurs primarily via increased hepatic levels of bacterial LPS that binds to TRL-4 on Kupffer and hepatic stellate cells (HSCs), increasing the transcriptional activation of proinflammatory genes and cytokines, such as IL-1β and TNF-α, in the liver via the MyD88 and NF-κB pathways and interferon (IFN) regulatory factors [125,131].…”