The intestinal short chain fatty acid production: its complexity and metabolic consequences

Recommendation of high fiber diets have been suggested as a valuable strategy to reduce the burden of metabolic diseases such as obesity, metabolic-associated fatty liver disease, and type 2 diabetes. In this context, gut microbiota has a pivotal role influencing host health. Acetate, propionate, and butyrate, the main short chain fatty acids (SCFA) produced by gut microbial fermentation of fibers, appear to be key mediators of the beneficial effects elicited by high fiber diets. However, while many studies focus on the regulatory role of SCFA, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. SCFA are also an extra source of energy from otherwise indigestible carbohydrates. To understand what controls the net effect of SCFA supplementation, more precise data on intestinal SCFA kinetics and their effect directly in other tissues is needed. Part I of the thesis (chapter 2, chapter 3, and chapter 4) aimed to study fiber fermentation and SCFA production, microbial interconversion, and absorption inside the lumen of the human gut in vivo, and the systemic metabolic fate of intestinal SCFA. Moreover, to further understand the mechanism by which SCFA can modulate host health, Part II of the thesis (chapter 5 and chapter 6), assessed the tissue specific effects of a single SCFA, butyrate, on fuel handling. This thesis raises important considerations for the study and development of dietary strategies for the prevention and treatment of metabolic syndrome.