**2. Short-Chain Fatty Acids (SCFAs)**

Short-chain fatty acids (SCFA) are the end products of microbial fermentation activity. Dietary fibre escapes digestion and absorption in the small intestine and is metabolised in the colon and cecum, from which mainly acetate, propionate, butyrate, and formate are generated; while lactate is obtained from the fermentation of selected non-digestible carbohydrates, which are often also rapidly metabolised into acetate, propionate, and butyrate [28,29]. Within the intestinal microbial flora, the bacterial species most involved in SCFAs production are *Butyricicoccus* spp., *Faecalibacterium prausnitzii*, *Roseburia* spp., *Bacterioides* spp. and *Bifidobacterium*, converting dietary fibre in the gut into monosaccharides through a series of reactions mediated by specific enzymes. Acetate can be produced via acetyl–CoA or the Wood–Ljungdahl pathway; propionate is produced by the conversion of succinate to methylmalonyl-CoA via the succinate pathway or can be synthesised from acrylate with lactate as a precursor via the acrylate pathway and via the propanediol pathway; butyrate is formed either via the classical pathway by reduction by phosphotransbutyl kinase and butyrate kinase, or via the butyryl-CoA/acetate CoA-transferase pathway. In addition, some microbes in the gut can use both lactate and acetate to synthesise butyrate [30,31]. However, when fermentable fibres are scarce, microbes exploit less favourable energy sources for SCFAs production, such as amino acids from dietary or endogenous proteins, or dietary fat, also producing branched-chain fatty acids [32,33]. Although the intestinal lumen is the main site of SCFA production, their concentration varies both throughout the intestinal tract and systemically [34]. Butyrate is absorbed by the intestinal epithelium and consumed locally because it is the main energy source of colonocytes [35], while propionate and acetate cross the portal vein so that the former is metabolised in the liver [36], and the latter remains the most abundant SCFAs in the peripheral circulation, reaching organs such as the brain, pancreas, muscle, and adipose tissue, where it regulates several physiological functions [37]. In fact, SCFAs also play a key role in organs outside the digestive tract because numerous transmembrane proteins, receptors and transporters that specifically bind SCFAs and other monocarboxylic acids are expressed in a wide variety of cells [38,39]. Thus, SCFAs are associated with human health benefits for both their metabolic and/or structural properties and their signalling properties.
