Microbiome, Multi-Omics, and Drosophila Models for Sex/Gender-Aware Precision Prevention in Cardiometabolic and Brain Health

We provide expertise in systems biology and integrative multi-omics to understand how the gut microbiome and host metabolism shape cardiometabolic and brain health, with an explicit sex/gender and life-course perspective (including obesity and menopause). We combine shotgun metagenomics with targeted and global metabolomics (NMR and LC–MS/MS), additional molecular layers where available (e.g. RNA-seq), and advanced computational pipelines (multi-omics integration, machine learning, pathway/network modelling) to identify actionable biomarkers and mechanisms.

Cohort assets (discovery + replication)

1) Six longitudinal obesity case–control cohorts (with menopause data, deep cardiometabolic phenotyping):
IRONMET (N=180), IRONMET+CGM (N=120), IRONmiRNA (N=127), METASUCC (N=93), GMB CrossTalkFood (N=91), POINTSETIA (N=100)

Across these cohorts we have:

• Fecal shotgun metagenomics (all 6)

• Global plasma metabolomics (>900 metabolites with 90% confidence)

• Global Adipose Tissue metabolomics (POINTSETIA)

• Menopause status (all 6)

• Cardiovascular-relevant clinical profiling: brachial blood pressure and heart rate, cardiometabolic biochemistry (lipid panel, glucose/HbA1c, hs-CRP, creatinine/urea/uric acid), anthropometrics (BMI, waist, WHtR, hip), lifestyle (smoking, alcohol), diet (93-item questionnaire), and medication records.

• Added depth in subsets: 10-day Dexcom G6 CGM (IRONMET+CGM, IRONmiRNA, GMB CrossTalkFood) and hyperinsulinemic clamp (IRONMET).

• Additional molecular layers where available: plasma miRNA (IRONMET+CGM, IRONmiRNA) and VAT 16S/RNA-seq in IRONMET and POINTSETIA.

• Complete biochemistry, medical and family history, body composition (DXA), etc

• 1-2 year follow-up (IRONMET, IRONMET+CGM, IRONmiRNA) and 2-5 year follow-up (POINTSETIA)

2) Two large-scale population cohorts (N≈2,000 participants):

• Health IMAGEOMICS: 1,060 participants (18–50 years)

• Aging IMAGEOMICS: 1,030 participants (50–99 years)

  These cohorts include:

• shotgun metagenomics

• plasma metabolomics (global profiling; ~400 and ~1000 metabolites, respectively),

• MRI-based phenotyping (brain volumes/DTI and multi-organ imaging including heart and fat distribution),

• cardiometabolic traits (blood pressure, lipids, glucose/HbA1c; arterial rigidity),

• lifestyle (Diet, smoking, alcohot, sleep apena, Physical activity, pollution)

• mental/behavioral measures (PHQ-9; additional domains in subsets).

Translational bridge

We complement human discovery with Drosophila melanogaster as an efficient in vivo platform for rapid mechanistic validation and screening of candidate microbes/metabolites/genes, reducing dependence on mouse experimentation.

Selected publication (sex dimorphism / menopause)

Mayneris-Perxachs J. et al. Gut microbiota steroid sexual dimorphism and its impact on gonadal steroids: influences of obesity and menopausal status. Microbiome (2020) 8:136.