**3. Short-chain fatty acids (SCFAs)**

There is increased attention on SCFAs given its importance in the human gut microbiota. The human microbiota is primarily the collection of microbes that live on and in our body, where the largest and most diverse cluster of microorganisms inhabits the gut [20]. Evidence has surfaced that the gut microbiota has coevolved with the host, which provides the microbes with a stable environment, while the microbes provide the host with a broad range of functions such as digestion of complex dietary macronutrients, production of nutrients and vitamins, defense against pathogens, and maintenance of the immune system [20]. Interactions between the microbiota and the distal gut are currently considered as fundamental determinants of human health.

As previously mentioned, SCFAs are a subset of saturated fatty acids containing six or less carbon molecules which include acetate, propionate, butyrate, pentanoic

(valeric) acid, and hexanoic (caproic) acid. SCFAs are the primary end products of fermentation of nondigestible carbohydrates that become available to the gut microbiota [21]. SCFAs represent the major flow of carbon from the diet, through the gut microbiome to the host. It was discovered recently that SCFA appears to be the natural ligands for free fatty acid receptors 2 and 3 (FFAR 2/3), found on a wide range of cell types, including enteroendocrine and immune cells [22–24]. This unearthing has led to renewed interest in the role of SCFA in human health.

SCFAs are mainly produced through saccharolytic fermentation of carbohydrates which are able to escape digestion and absorption in the small intestine [21, 25]. The pathways of SCFA production are well understood at present and have been recently described in detail recently by Flint et al. [26]. The major products formed as a result of the saccharolytic fermentation are formate, acetate, propionate, and butyrate. Lactate is also a major organic acid produced from the fermentation of selected often rapidly fermentable nondigestible carbohydrates [21]. Relatively minor amounts of branched-chain fatty acids are also produced in this biochemical pathway, mainly through the fermentation process of protein-derived branched-chain amino acids [27, 28].

Acetate is the most abundant SCFA in the colon and makes up more than half of the total SCFA detected in feces [29, 30]. The majority of acetate is produced by most of the enteric bacteria present in the gut as a result of carbohydrate fermentation [30]. In addition, approximately one-third of the colonic acetate has been detected to come from acetogenic bacteria, which are able to synthesize it from hydrogen and carbon dioxide or formic acid through the Wood-Ljungdahl pathway [25, 31].

It is evident from the insurmountable evidence on microbial interactions with dietary polysaccharides and the resulting SCFAs that these particular fatty acids are important energy and signaling molecules. It is becoming increasingly accepted that SCFA-producing bacteria have several beneficial effects on human health. However, it is still unclear whether beneficial effects are driven by the SCFAs per se or whether in combination with other metabolites produced from the gut bacteria [20]. It should be noted and understood in this instance that the gut microbiota produces many other classes of metabolites such as bile acids and amino acid derivatives, which may also have several essential signaling functions leading to health and wellness of the human physiological systems.
