Background: 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. Methods: 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. Conclusions: 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.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common metabolic liver disease with increasing prevalence worldwide. Increasing evidence suggests that short-chain fatty acids (SCFAs) play an important role in MASLD. Medium-chain fatty acids (MCFAs), although less studied, may also contribute to MASLD pathogenesis. The aim of this study was to evaluate plasma SCFA and MCFA profiles across the MASLD histological spectrum and their associations with clinical, biochemical, and histopathological features of disease severity. Methods: We included 115 adults with obesity undergoing bariatric surgery. Intraoperative liver biopsies were assessed using the Steatosis, Activity, Fibrosis (SAF) score. Participants were classified as no MASLD (n = 26), metabolic dysfunction-associated steatotic liver (MASL; n = 42), or metabolic dysfunction-associated steatohepatitis (MASH; n = 47). Six SCFAs and two MCFAs were quantified in plasma by liquid chromatography–mass spectrometry. Results: Patients with MASH showed lower acetate and higher hexanoate plasma levels than those without MASLD. Acetate was inversely associated with ALT, AST, GGT, glucose, HbA1c, cytokeratin-18, SAF score, steatosis and lobular inflammation, whereas hexanoate was positively associated with SAF score and lobular inflammation. Higher acetate concentrations were independently associated with lower odds of MASH (OR 0.973; p = 0.040), while ALT levels were independently associated with increased odds of MASH (OR 1.083, p = 0.001). Conclusions: MASH in patients with obesity is characterized by a distinct circulating fatty acid profile, with reduced acetate and increased hexanoate. Lower acetate levels were independently associated with MASH and markers of metabolic and histological disease severity.