# In Vitro Simulation of Human Colonic Fermentation:
## 3 The Colonic Fermentation Process  
The large intestine is a suitable environment (pH between 6-8 and anaerobic conditions) for the development of microorganism populations (colonic microbiota), most of which belong to the Bacteroidetes and Firmicutes phyla [15]. The main biochemical reaction occurring in the colon is fermentation, which produces a series of metabolites used by both the microorganisms and the host as a source of energy [16]. Nevertheless, it is also involved in the modulation of other body functions, such as the immune system and the brain-gut axis. The preferent substrates for the microbiota are non-digestible carbohydrates, including fibre, cellulose, hemicellulose, pectin, gums, and alginates. The colonic fermentation of these macromolecules results in short-chain fatty acid (SCFA) production, mainly acetate, butyrate, and propionate, and gas, such as hydrogen and carbon dioxide [17]. When the source of non-digestible carbohydrates is limited, the microbiota utilises protein substrates, generating sulphurated and N-nitro compounds, ammoniac, heterocyclic amines, and branched-chain fatty acids (BCFA). On the other hand, most dietary lipids are digested and absorbed in the small intestine and do not reach the colon. However, when lipid intake is high, bile salt secretion increases, and the excess that is not absorbed along with lipids passes on to the colon and can be fermented by the microbiota, producing secondary bile salts [18]. In general terms, from the main metabolites generated by the microbiota, SCFA seem to be related to beneficial health effects, while sulphur compounds and secondary bile salts have been associated with harmful outcomes [16; 17; 18]. However, despite the acknowledgement of the important role that the microbiota plays in food digestion and the effect that food constituents have on promoting or reducing certain microbiota populations, many gaps in establishing explanations remain. Even though some generalization about the species comprising the microbiota can be made [15], a wide diversity of factors (lifestyle, habitat, birth delivery mode, maternal nutritional status, or breastfeeding, among others) determine a specific microbiota profile in each individual. Eating habits and type of diet have a major impact [19] and can be modified, serving as a tool to modulate the microbiota composition. In particular, the effect of carbohydrates has been widely studied, as they are the main substrate for intestinal microorganisms [20]. Among them, non-digestible carbohydrates arrive in their native form to the colon and are fermented by the microbiota promoting their growth  
Figure 1: Flow diagram of data selection and identification process. and activity, subsequently generating beneficial compounds for health [21]. In upper gut digestion, digestible carbohydrates are broken down into oligosaccharides, disaccharides, and monosaccharides and are absorbed before reaching the colon. Nevertheless, in high-sugar diets, they can reach the colon since the absorption capacity of the small intestine is exceeded, thus causing losses in microbial diversity [22]. Similarly, protein and lipid intake can also lead to changes in microbiota composition. Diets rich in animal-origin protein and low-digestible carbohydrates lead to the microbial production of metabolites (BCFA, N-nitroos compounds) related to the increased risk of suffering from colorectal disorders [23]. In the case of fatty acids, monosaturated fatty acids and n-3 polyunsaturated fatty acids have been associated with an increase in beneficial bacteria and the production of SCFA, while diets rich in long-chain fatty acids have the opposite effect [24]. Furthermore, a wide diversity of diets is available worldwide depending on the ecosystem and cultural, economic, or agronomic considerations. This is probably the reason behind the differences in the microbiota profile observed from distinct geographical regions [20]. In this aspect, [PERSON] et al.