Can Early Nutrition Be Responsible for Future Gut Microbiota Changes and Different Health Outcomes?

Abstract

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.

Keywords: Mediterranean diet; chronic inflammatory diseases; complementary feeding; gut microbiota; public health.

Figure 1

Correlation between BMI and Kidmed score in the overall sample.

Figure 2

Analysis of gut microbiota composition. (A) PCoA plane based on Bray–Curtis distance showing differences in the intestinal microbiota between MD and controls at nine years. Each point represents a sample. (B) Boxplots showing the longitudinal within-group alpha diversity of the gut microbiota. Each point represents a sample, and the horizontal gray lines connect samples from the same subject. (C) Boxplot comparing the relative abundance (%, on the y-axis) of Ruminococcus bromii between samples collected from the same subjects at different timepoints (3 and 9 years). Each point represents a sample. The horizontal gray lines connect samples from the same subject.