Introduction

Dietary lipids, or fats, are an important source of energy in most people's diet. An average Western diet might include 100 g of lipids, of which ~95% are triglycerides (TAGs), consisting of three hydrophobic fatty acids attached to a glycerol backbone. This hydrophobic nature causes TAG molecules to aggregate and self-assemble, forming spherical micelles when exposed to aqueous environments. Fatty acid side chains exhibit a remarkable diversity in both length and degree of unsaturation, significantly influencing the structure and properties of TAG molecules. The most important fatty acids are highlighted in Table 1, below.

Table 1. Sources of important fatty acids in humans (Kaur2014a). Note: the importance of 'trans fats', such as trans-18:1 FA, is still being debated. It is recommended that less than 30% of the diet-derived energy comes from fats, and that trans fats are limited to 1% of this (2.2 g/day/average person; WHO).

Saturated fats typically come from the adipose tissue, meat and dairy products of animals, but can also be obtained from plant sources, such as coconut and palm oils (heart.org). These types of lipids are non-essential, meaning that humans are able to synthesise saturated fatty acids (FAs) in the liver from other dietary inputs (AlvesBezerra2017). Essential fatty acids include polyunsaturated forms derived from fish, seeds, vegetable oils and leafy green vegetables (Kaur2014a). As the name implies, these FAs can't be synthesised by the body and are essential for cellular membrane integrity, brain and nervous system function, and the immune system, among others (Lunn2006).

Irrespective of the fat source or type of fatty acids, the digestive process remains consistent: fats from ingested food undergo partial digestion and dispersion in the mouth and stomach, while the primary digestion takes place in the duodenum and proximal jejunum of the small intestine. This is the pivotal site where the majority of the broken-down fats are absorbed (see Figure 1).

Figure 1. Fat, predominantly present as triglycerides, exhibits a tendency to aggregate. The initial stages of lipid dispersal and triglyceride hydrolysis commence with chewing and the release of lingual lipase. Subsequently, in the stomach, further breakdown is facilitated by the release of gastric lipase, which functions optimally within a pH range of 3 to 6. When the fat-infused chyme is emptied into the duodenum, it triggers the release of cholecystokinin, an enteric hormone responsible for stimulating the gall bladder to release bile. Additionally, upon detecting acidity, the production of secretin is triggered, which, in turn, stimulates the release of bicarbonate and water into the bile duct. Pancreatic lipase is secreted from the pancreas and, in conjunction with bile, culminates the process of fat digestion by forming soluble mixed micelles, which are easily processed by the small intestine. The remaining bile salts make their way to the ileum, where they are absorbed and subsequently recycled through the liver. It's worth noting that bilirubin, a constituent of bile and a waste product derived from the breakdown of red blood cells, is excreted in the faeces.

Process of fat digestion

Dietary fats tend to aggregate into water-insoluble globules of varying sizes, necessitating both physical and chemical breakdown processes to form smaller particles that the body can effectively absorb. The location and absorption of lipids in humans is summarised in Figure 2. Lipid digestion in the mouth and stomach is relatively limited, accounting for approximately 30% of the breakdown. The process initiates with physical breakdown, and the sequential release of lingual lipase and gastric lipase triggers the hydrolysis of TAGs into diglycerides (DAGs), monoglycerides (MAGs), and free FAs. These lipases are activated with low pH and continue their work until the stomach contents is emptied into the duodenum, where the higher pH inactivates them.

Figure 2. The breakdown of fats begins in the mouth and stomach, where lingual and gastric lipases start breaking down lipid droplets. However, the primary digestion, as well as the absorption, takes place in the small intestine. Malabsorption of fats can result in steatorrhoea, a condition where excess fats are improperly absorbed and end up in the colon, leading to their excretion.

Upon reaching the duodenum, the fat droplets present in the stomach contents undergo additional breakdown and dispersion through the action of lipases and emulsification facilitated by bile (see next section). The role of bile in fat digestion encompasses two crucial functions: firstly, the incorporation of bile salts into the outer layer of micelles vastly amplifies the lipid surface area by over a thousand-fold, enabling digestive enzymes to efficiently access glyceride molecules. Secondly, bile facilitates the transformation of smaller micelles into a water-soluble form, aiding in their absorption and utilisation (Hofmann1987).

Figure 3. The enterocytes in the jejunum efficiently process water-soluble mixed micelles containing bile salts, fatty acids, monoglycerides, cholesterol, and phospholipids. Apart from the bile salts, the components of the micelle are absorbed, acylated, and then reassembled into a transportable form known as a chylomicron. Unlike other nutrients, transportation of these chylomicrons occurs through the lymphatic system, rather than the bloodstream.

Bile and its impact on the gut microbiome

Bile constitutes a complex mixture of water-soluble constituents (refer to Table 2), amphiphilic components like bile salts and phospholipids, as well as lipophilic cholesterol (Figure 4). In addition to its role in emulsifying fats, bile plays a significant role as a major route for excreting various products from the liver. These products include bilirubin, a breakdown product of degraded erythrocytes, excess cholesterol, and potentially harmful exogenous lipophilic compounds (Boyer2013). Bile also helps prevent enteric infections by secreting immunoglobulin A, inflammatory cytokines, and stimulating the innate immune system in the intestine.

Table 2.

Bile acid salts (BA), which are synthesised in the liver from cholesterol, undergo a process of recovery primarily in the ileum and subsequently reenter enterohepatic circulation (Ticho2019). This circulation is important for maintaining the pool of bile acids within the system (Boyer2013). Over a dozen primary and secondary salt derivatives are contained within human bile, although cholic acid and chenodeoxycholic acid are mostly dominant (Figure 4).

Figure 4. Chemical structures of key compounds found in human bile. Important bile acid salts are illustrated (right). Among these, cholic and chenodeoxycholic acids are essential bile acids (right). These primary bile acids can undergo conjugation with glycine to form glycocholic acid or with taurine to form taurocholic acid. Furthermore, primary bile acids can undergo metabolism by gut bacteria, leading to the production of bioactive secondary bile acids, such as deoxycholic and lithocholic acids. These secondary bile acids hold biological significance and further contribute to the complexity of bile acid interactions within the gastrointestinal tract.

The surfactant properties of bile salts can pose a toxic effect on both epithelial cells and various gut bacteria. Consequently, the regulation and recycling of bile acid salts are of importance in shaping the microbiome ecology. Interestingly, it seems that both the host and the microbiome are involved in regulating bile acid concentrations in the gut, while the bile salts, in turn, can influence the composition of the microbiome community (Ridlon2014). Examples of important bacteria that interact with bile salts is outlined in Table 3, below.

Table 3. Dominant bacteria that are susceptible (left) or tolerant (right) to bile salts (Pu.biome).

Under normal circumstances, around 95% of bile salts are absorbed, with the remaining portion being released into the colon and eventually excreted (Ticho2019). This results in around 0.6 mmol of BA / 300 g faeces (Vijayvargiya2020), while caecum concentrations reach ~0.43 ± 0.19 mM of total BAs (Hamilton2007).

It is important to note that the measurement of bile acids in the gastrointestinal tract is more complex than a simple excretion process. In fact, very few primary bile acids, such as cholic acid and chenodeoxycholic acid, are directly excreted. Instead, they undergo further metabolism by gut bacteria (Thomas2001). For example, deoxycholic acid (DCA) is derived from the bacterial metabolism of cholic acid. DCA possesses greater relative hydrophobicity and detergent properties, leading to significantly increased antibacterial activity compared to its parent compound, cholic acid (Ridlon2014). This highlights the dynamic interplay between bile acids and the gut microbiota, with potential implications for gut health and bacterial ecology.