METABOLICALLY HEALTHY AND UNHEALTHY OBESITY IN CHILDREN AND ADOLESCENTS: DIETARY IMPLICATIONS AND NEW OPPORTUNITIES FOR GUT MICROBIOTA MODULATION

This doctoral dissertation aimed to evaluate strategies for modulating gut microbiota composition in children and adolescents with metabolically healthy and unhealthy obesity. Three main projects were carried out: (1) a systematic review and metanalysis on the role of dietary intervention in modulating gut microbiota, and two clinical trials (2) the DAMOCLE study and (3) the PolyMets Study, both oriented towards investigating the efficacy of bioactive compounds as complementary strategies to act on gut microbiota composition. A systematic review and meta-analysis were conducted to assess the effects of dietary interventions on gut dysbiosis in pediatric obesity. After screening 47 studies, five were included, focusing on calorie-restricted or low-sugar diets. Meta-analysis revealed significant improvements in gut microbiota alpha diversity following calorie restriction, including an increase in butyrate-producing bacteria, namely Faecalibacterium and Roseburia, which are linked to improved cardiometabolic health. The DAMOCLE study evaluated the impact of docosahexaenoic acid (DHA) supplementation in 18 obese children. Results showed that DHA supplementation (500 mg/day) helped restore the Firmicutes/Bacteroidetes ratio, with sustained effects even after discontinuation. DHA supplementation drove a depletion in Ruminococcaceae and Dialisteraceae, and enrichment in Bacteroidaceae, Oscillospiraceae, and Akkermansiaceae. At genus level, Allisonella was the most decreased by DHA supplementation. In vitro, DHA demonstrated anti-inflammatory properties by reducing oxidative stress and modulating cytokine production in Caco-2 cells. The PolyMets study examined the effects of a polysaccharidic macromolecule supplement (5 g/day of mixed fibres) combined with dietary and lifestyle interventions in 36 children with metabolically unhealthy obesity (MUO). Intervention led to improvements in BMI, biochemical parameters, and gut microbiota composition. The supplementation itself reduced obesity-associated bacterial families such as Monoglobaceae and Erysipelatoclostridiaceae. A non-significant reduction in the Firmicutes/Bacteroidetes ratio was also observed, and polysaccharidic macromolecules also contributed to a significant reduction in total fat mass and increases in fat-free mass. Overall, dietary interventions alone can improve gut microbiota diversity, yet bioactive compounds such as DHA and polysaccharide macromolecules represent a tool that can optimise changes in the gut microbiota and effects on cardio-metabolic parameters in paediatric obesity.