Feed and Food for Global Health

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognised as a global health burden, closely associated with obesity and metabolic syndrome. MASLD is influenced by genetic predisposition and environmental factors, highlighting the need for effective management strategies. The integration of diet and physical activity modifications is crucial to mitigate disease progression and improve liver health. Through the Feed and Food for Global Health study, this PhD thesis aimed to explore the efficacy of customised dietary interventions on patients with MASLD, and to characterise and examine the response of their gut microbiota to various dietary products. The specific objectives were: 1) To evaluate the impact of three 6-month dietary interventions (low-carbohydrate diet, mediterranean diet, and control diet) on the hepatic and metabolic parameters of patients with MASLD. 2) To analyse the composition of the gut microbiota composition of patients at baseline and after the 6-month dietary intervention. 3) To investigate the effects of different protein sources on the gut microbiota of a healthy donor with the gastrointestinal simulator SHIME®. 4) To examinate the influence of different types of nuts on the gut microbiota of two selected patients with MASLD who followed the dietary intervention, using the SHIME® system. The results of this thesis demonstrated significant improvements in liver health, body composition and metabolic status in patients with MASLD across all dietary interventions examined. Importantly, no diet proved to be superior to the others; instead, the results suggest that the effectiveness of a diet in the management of MASLD depends on its ability to be tailored to individuals' needs and preferences, thereby improving adherence and long-term sustainability. Notably, weight loss emerged as a significant predictor of improvement in hepatic steatosis, emphasising that weight management, rather than adherence to a certain diet at the expense of another, is a key component in the therapeutic strategy against MASLD. In addition, the 16S analysis conducted on patients who adhered to the 6-month dietary intervention at baseline and at the end of the study showed that dietary modifications led to significant changes in the composition of the gut microbiota. In particular, the mediterranean and low-carbohydrate diets exerted a marked influence on microbiota diversity, highlighting the role of diet in modulating this crucial aspect of gut and, by extension, liver health. Furthermore, SHIME® experiments conducted on various protein sources and different types of nuts revealed different effects on the gut microbiota. These results highlight the importance of careful food selection to optimally modulate microbial responses. In summary, the study emphasises the critical interaction between diet and gut microbiota in the management of MASLD, supporting the need for personalised nutrition as a key component of therapeutic strategies. This approach would not only promote immediate improvements in health parameters, but also sustained dietary habits that may continue to benefit liver health and general well-being.