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

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.

[1]  S. Lai,et al.  Cocaethylene, simultaneous alcohol and cocaine use, and liver fibrosis in people living with and without HIV , 2022, Drug and Alcohol Dependence.

[2]  J. Fallowfield,et al.  All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: a UK Biobank study , 2021, BMC Public Health.

[3]  Jun Chen,et al.  Food insecurity is associated with magnetic resonance-determined nonalcoholic fatty liver and liver fibrosis in low-income, middle-aged adults with and without HIV. , 2021, The American journal of clinical nutrition.

[4]  F. Lammert,et al.  Prediction of advanced fibrosis in non-alcoholic fatty liver disease using gut microbiota-based approaches compared with simple non-invasive tools , 2020, Scientific Reports.

[5]  Giri Narasimhan,et al.  So you think you can PLS-DA? , 2017, BMC Bioinformatics.

[6]  H. Fukui Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far? , 2019, Diseases.

[7]  William M. McFadden,et al.  High-fat diet exacerbates SIV pathogenesis and accelerates disease progression. , 2019, The Journal of clinical investigation.

[8]  Kelei Li,et al.  Fruit and vegetable intake and liver cancer risk: a meta-analysis of prospective cohort studies. , 2019, Food & function.

[9]  S. Iacob,et al.  Infectious Threats, the Intestinal Barrier, and Its Trojan Horse: Dysbiosis , 2019, Front. Microbiol..

[10]  William A. Walters,et al.  Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2 , 2019, Nature Biotechnology.

[11]  D. Graham,et al.  Dietary quality and the colonic mucosa-associated gut microbiome in humans. , 2019, The American journal of clinical nutrition.

[12]  Kyongbum Lee,et al.  Interactions between gut microbiota and non‐alcoholic liver disease: The role of microbiota‐derived metabolites , 2019, Pharmacological research.

[13]  S. Ng,et al.  Impact of Preservation Method and 16S rRNA Hypervariable Region on Gut Microbiota Profiling , 2019, mSystems.

[14]  Kathleen V Fitch,et al.  Diet Quality Is Low and Differs by Sex in People with HIV. , 2019, The Journal of nutrition.

[15]  S. Kirkpatrick,et al.  Evaluation of the Healthy Eating Index-2015. , 2018, Journal of the Academy of Nutrition and Dietetics.

[16]  O. Shibolet,et al.  High red and processed meat consumption is associated with non-alcoholic fatty liver disease and insulin resistance. , 2018, Journal of hepatology.

[17]  Dirk Jäger,et al.  MetaboDiff: an R package for differential metabolomic analysis , 2018, Bioinform..

[18]  Marju Orho-Melander,et al.  Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars , 2018, Diabetes Care.

[19]  S. Chanprasertyothin,et al.  The Association of Gut Microbiota with Nonalcoholic Steatohepatitis in Thais , 2018, BioMed research international.

[20]  R. Sterling,et al.  Mechanisms of liver disease in patients infected with HIV , 2017, BMJ open gastroenterology.

[21]  Jian-Gao Fan,et al.  Gut microbiota dysbiosis in patients with non-alcoholic fatty liver disease. , 2017, Hepatobiliary & pancreatic diseases international : HBPD INT.

[22]  T. Schulz,et al.  Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice , 2017, Scientific Reports.

[23]  R. Marlink,et al.  Prevalence and distribution of non-AIDS causes of death among HIV-infected individuals receiving antiretroviral therapy: a systematic review and meta-analysis , 2017, International journal of STD & AIDS.

[24]  Shibu Yooseph,et al.  Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease. , 2017, Cell metabolism.

[25]  A. Copas,et al.  Mortality and causes of death in people diagnosed with HIV in the era of highly active antiretroviral therapy compared with the general population: an analysis of a national observational cohort. , 2017, The Lancet. Public health.

[26]  M. Ferrer,et al.  Gut Bacteria Metabolism Impacts Immune Recovery in HIV-infected Individuals , 2016, EBioMedicine.

[27]  David L. Thomas,et al.  Human immunodeficiency virus and liver disease: An update , 2015, Hepatology.

[28]  Coral Barbas,et al.  Missing value imputation strategies for metabolomics data , 2015, Electrophoresis.

[29]  D. Cohen,et al.  Lipid and Lipoprotein Metabolism in Liver Disease , 2015 .

[30]  James E. Nelson,et al.  Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not β-cell function in humans. , 2014, The American journal of clinical nutrition.

[31]  Andmorgan R. Fisher,et al.  Altered profile of human gut microbiome is associated with cirrhosis and its complications. , 2014, Journal of hepatology.

[32]  Kholoud Porter,et al.  Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy , 2014, AIDS.

[33]  A. Kane,et al.  Associations of cocaine use and HIV infection with the intestinal microbiota, microbial translocation, and inflammation. , 2014, Journal of studies on alcohol and drugs.

[34]  Lawrence A. David,et al.  Diet rapidly and reproducibly alters the human gut microbiome , 2013, Nature.

[35]  R. Kaul,et al.  Mucosal Th17 Cell Function Is Altered during HIV Infection and Is an Independent Predictor of Systemic Immune Activation , 2013, The Journal of Immunology.

[36]  J. Kirwan,et al.  Increasing Whole Grain Intake as Part of Prevention and Treatment of Nonalcoholic Fatty Liver Disease , 2013, International journal of endocrinology.

[37]  Susan Holmes,et al.  phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census Data , 2013, PloS one.

[38]  L'âge moderne jusqu'en Center for Nutrition Policy and Promotion , 2011 .

[39]  Baoli Zhu,et al.  Characterization of fecal microbial communities in patients with liver cirrhosis , 2011, Hepatology.

[40]  Manolito Torralba,et al.  Enteric dysbiosis associated with a mouse model of alcoholic liver disease , 2011, Hepatology.

[41]  J. Kostman,et al.  Prevalence and risk factors for significant liver fibrosis among HIV-monoinfected patients , 2010, BMC infectious diseases.

[42]  L. Palmisano,et al.  Modifications of residual viraemia in human immunodeficiency virus-1-infected subjects undergoing repeated highly active antiretroviral therapy interruptions. , 2009, Journal of medical microbiology.

[43]  D. Baer,et al.  The US Department of Agriculture Automated Multiple-Pass Method reduces bias in the collection of energy intakes. , 2008, The American journal of clinical nutrition.

[44]  J. Montaner,et al.  Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection , 2006, Hepatology.

[45]  D. Drossman,et al.  The functional gastrointestinal disorders and the Rome III process. , 1999, Gastroenterology.

[46]  P. Tůma,et al.  Determination of 3-methylhistidine and 1-methylhistidine in untreated urine samples by capillary electrophoresis. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[47]  P. Dixon VEGAN, a package of R functions for community ecology , 2003 .

[48]  Martin Vingron,et al.  Variance stabilization applied to microarray data calibration and to the quantification of differential expression , 2002, ISMB.

[49]  Marti J. Anderson,et al.  A new method for non-parametric multivariate analysis of variance in ecology , 2001 .

[50]  M. Perdue Intestinal permeability. , 1988, Gut.