Short-chain fatty acids (SCFAs) are the primary metabolites produced in the large bowel by the anaerobic gut microbiome. They play an essential role in a wide variety of human diseases, including autoimmune diabetes, non-alcoholic liver disease, cirrhosis, neurodevelopmental disorders, atherosclerosis, obesity, some immune dysfunctions, cardiovascular diseases, and kidney diseases.
SCFAs may be the most crucial link between diet, gut microbiota, and human health.
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It is well known that multiple factors can alter the regular composition of the gut microbiota, favoring the onset of intestinal diseases, such as inflammatory bowel disease (IBD), celiac disease, and colorectal cancer. The diet represents one of the main documented elements responsible for changes in the structural and functional relationship between gut microbiota and the host. The fermentative bacterial metabolism of dietary components, especially indigestible fibers, produces many biologically active compounds, such as short-chain fatty acids (SCFAs).
SCFAs are saturated fatty acids composed of one to six carbons, of which acetic (C2), propionic (C3), and butyric (C4) are in the most significant quantity with a generally constant respective molecular ratio of 60:20:20 in the colon as well as in the feces. Besides these, other SCFAs, such as iso-butyric (C4), valeric (C5), and iso-valeric (C5), are present in lower amounts. They can be absorbed by the colonic epithelium, providing energy or entering the bloodstream, playing a relevant role in regulating the metabolism of fatty acids, glucose, and cholesterol. Moreover, thanks to their ability to induce the production of antimicrobial peptides and to modulate the number and functions of Regulatory T cells (Tregs), SCFAs contribute to the modulation of host immune responses. An unhealthy gut microbiome status reduces SCFAs’ concentration, essential for the host to prevent intestinal diseases. They preserve the epithelial barrier functionality and contrast the onset of inflammatory reactions by the transcriptional regulation of tight junction proteins, particularly the claudin-1, and particularly butyrate, which may block the translocation of lipopolysaccharide, a potent pro-inflammatory molecule. In addition, the SCFAs sustain the proliferation and differentiation of colonocytes and protect colonic epithelium by increasing the expression of mucin 2 and modulating both oxidative stress and immune response.
Different studies have well documented an alteration in SCFAs’ composition in some human pathologies, such as IBD, irritable bowel syndrome, diarrhea, and cancer. For this reason, they represent a target to measure intestinal health and have been proposed as potential diagnostic biomarkers. Moreover, the SCFAs’ evaluation in stool samples is a faster and more reliable method to highlight the presence of intestinal dysbiosis instead of the microbiota characterization. Besides, genomics approaches cannot shed light on actual fermentation processes and functional microbiota changes (metabolite production).
SCFAs have numerous mechanistic links to host health. They may play essential roles in energy metabolism, satiety promotion, gut barrier function maintenance, immune function, anti-inflammatory responses, and colon carcinogenesis. They are readily absorbed through the colonic lumen and account for roughly 10% of the daily caloric intake. Beneficially, they may reduce plasma fatty acids, cholesterol, and glucose levels. SCFAs act as an energy source for colonocytes via beta-oxidation and influence cell proliferation rates by releasing growth factors, modulating mucosal blood flow, and through genes involved with the cell cycle.
