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HELIUS: Baseline gut microbiota and incident cardiometabolic diagnoses

This repository contains the analysis code for a longitudinal study examining associations between baseline gut microbiota composition and incident cardiometabolic diagnoses (type 2 diabetes, hypertension, dyslipidemia) in a multi-ethnic urban cohort. Data are from the HELIUS study (Healthy Life in an Urban Setting), Amsterdam, the Netherlands.

Contact: b.j.verhaar@amsterdamumc.nl


Study overview

  • Cohort: HELIUS — a multi-ethnic cohort including Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan participants
  • Design: Longitudinal (baseline + follow-up), with 16S rRNA gut microbiota profiling at baseline and cardiometabolic outcomes assessed at follow-up
  • Outcomes: New-onset type 2 diabetes, hypertension, and dyslipidemia
  • Microbiome data: 16S rRNA amplicon sequencing, rarefied phyloseq objects (ASV-level)
  • Additional data: Untargeted plasma metabolomics (Metabolon platform, paired baseline/follow-up)

Repository structure

├── scripts/
├── data/       # Input data (not tracked in git)
└── results/    # Output figures and tables

Scripts

Script Description
1a_datacleaning.R Merges and cleans HELIUS clinical data (SPSS), constructs incident diagnosis flags (DM_new, HT_new, Dyslip_new), and prepares the rarefied phyloseq object matched to participants with follow-up data
1b_metabolomics.R Cleans and log10-transforms Metabolon untargeted metabolomics data; aligns subject IDs across baseline and follow-up
1c_datacleaning_allbaseline.R Prepares the complete baseline dataset including participants without follow-up, used for sensitivity analyses
1d_rarefaction_curve.R Generates rarefaction curves to assess sequencing depth adequacy
2_table1.R Descriptive statistics (Table 1 by timepoint/sex; ethnicity-stratified table; metabolomics subset table) using tableone
3_diversity_ordination.R Alpha diversity (Shannon, richness, Faith's PD) and Bray-Curtis PCoA with PERMANOVA, stratified by incident diagnosis
4a_microbes_diagnoses.R ASV-level logistic regression (CLR-transformed) for incident diabetes, hypertension, and dyslipidemia; two models (age-adjusted; fully adjusted); FDR correction; forest plots
4b_microbes_diagnoses_ethnicity.R As 4a, with ethnicity interaction terms
4c_microbes_diagnoses_sex.R As 4a, with sex interaction terms
5_metabolites_microbes.R Linear regression of plasma metabolites on diagnosis-associated ASVs

Dependencies

The analyses use R (≥ 4.1). Package dependencies are managed with renv; restore the environment with:

renv::restore()

Key packages:

  • Data handling: tidyverse, haven, rio
  • Microbiome: phyloseq, vegan, picante
  • Statistics: broom, tableone, compositions
  • Visualization: ggplot2, ggpubr, patchwork, ggsci, ggthemes, ggrepel

Execution order

Scripts should be run in the order indicated by their filename numbering.

About

Analyses on gut microbiota composition and longitudinal new-onset cardiometabolic diagnoses in the HELIUS cohort.

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