Dynamics of the Epigenome, Microbiome, and Metabolome in Relation to Early Adiposity in the Maternal–Infant Axis: Protocol for a Prospective, Observational Pilot Study in the Spanish NEMO Cohort

<b>Background:</b> Childhood obesity has reached epidemic levels in developed countries and is an emerging concern in developing regions. Children with excess weight are more likely to maintain this condition over time into adulthood and face a higher risk of developing metabolic disorders such as type 2 diabetes, hypertension, metabolic dysfunction-associated liver disease, and dyslipidemia. Early identification of obesity risk is, therefore, a key public health challenge. <b>Methods:</b> This is an observational, prospective, single-center cohort pilot study in 66 mother-infant dyads recruited at the Gynecology and Obstetrics Service of the Virgen de la Arrixaca University Hospital (Murcia, Spain). The primary objective is to identify early-life, non-invasive biomarkers associated with increased adiposity by integrating multi-omics approaches and analyzing maternal-infant interactions. Pregnant women will be enrolled during the third trimester and will undergo a baseline visit at 38 weeks of gestation for clinical and anthropometric assessment. Buccal swabs and fecal samples will be collected at baseline and in the peripartum period for epigenetic (DNA methylation), metagenomic, and metabolomic analyses. Infants will be evaluated at birth and followed at 6 months, 1 year, 2 years, and 3 years. Each visit will include detailed anthropometric measurements, along with collection of buccal swabs and fecal samples for multi-omics profiling. <b>Conclusions:</b> This multidisciplinary study aims to assess how maternal factors influence infant epigenetic and microbial patterns, and their relation to adiposity development. Early identification of such biomarkers may guide personalized prevention strategies and reduce the long-term burden of obesity-related comorbidities.