Mediterranean Diet (Med Diet) is one of the healthiest dietary patterns. We aimed to verify the effects of weaning (i.e., the introduction of solid foods in infants previously fed only with milk) using adult foods typical of Med Diet on children eating habits, and on the microbiota composition. A randomized controlled clinical trial on 394 healthy infants randomized in a 1:1 ratio in a Med Diet group weaned with fresh; seasonal and tasty foods of Med Diet and control group predominantly weaned with industrial baby foods. The primary end point was the percentage of children showing a good adherence to Med Diet at 36 months. Secondary end points were mother’s changes in adherence to Med Diet and differences in children gut microbiota. At 36 months, children showing a good adherence to Med Diet were 59.3% in the Med Diet group and 34.3% in the control group (p < 0.001). An increase in adherence to the Med Diet was observed in the mothers of the Med Diet group children (p < 0.001). At 4 years of age children in the Med Diet group had a higher gut microbial diversity and a higher abundance of beneficial taxa. A Mediterranean weaning with adult food may become a strategy for early nutritional education, to develop a healthy microbiota, to prevent inflammatory chronic diseases and to ameliorate eating habits in children and their families.

Background/Objectives: Chronic inflammatory diseases (CIDs) often present a preclinical phase influenced by genetic and environmental factors, including nutrition. Early dietary habits may modulate long-term health trajectories by shaping the intestinal microbiota. Previous work showed that weaning with fresh foods from the Mediterranean diet (MD) improved dietary habits and microbiota composition at 3 years of age. This study aimed to assess whether such benefits persist at 9 years. Methods: This long-term follow-up included 191 children (96 MD, 95 controls) from the original randomized cohort (ClinicalTrials.gov NCT05297357). The primary endpoint was adherence to MD (KidMed score ≥ 8). Secondary endpoints included BMI, incidence of CID, maternal dietary adherence, and intestinal microbiota composition in a subset of 36 children. Results: At 9 years, no difference was found in overall MD adherence (27.4% controls vs. 27.1% MD; p > 0.99) or BMI (17.7 vs. 18.1 kg/m²; p = 0.384). However, children from the MD group reported higher daily vegetable intake (71.9% vs. 51.6%; p = 0.005). Microbiota analyses revealed persistent differences between groups, with higher alpha diversity in the MD group. Although not statistically significant, the MD group showed lower prevalence of atopic dermatitis, allergic rhinitis, autism spectrum disorder, and ADHD. Maternal adherence to MD did not differ between groups. Conclusions: Early introduction of Mediterranean-style foods during weaning exerts lasting effects on dietary patterns and gut microbiota, with a potential protective trend against CID. While overall MD adherence converged between groups by 9 years, these findings suggest that early-life nutritional interventions may induce durable microbiome-mediated benefits and contribute to preventive strategies for chronic disease, warranting confirmation in larger, extended cohorts. Moreover, this study highlights the value of the collaboration between the Italian primary care pediatric system and the integration of the pediatric residency program, demonstrating a feasible and cost-effective methodology to generate large-scale prospective data within routine clinical practice. Larger studies and a longer follow-up period are necessary to confirm these results.