Interplay between Western Diet, Gut Microbiota, and Cancer Development

Background

A complex interplay between several modifiable factors, including diet, lifestyle, and environment, significantly increases the risk of cancer development. However, these factors can be amenably modified to reduce the cancer risk. 

A healthy diet refers to moderate saturated fat, sugar, sodium, and cholesterol consumption. However, the diet mostly followed in Western countries contains a high amount of these unhealthy food items.

Studies have shown that continued adherence to a Western diet can increase the risk of various diseases, including cardiovascular disease, diabetes, obesity, and certain cancers. As a major source of microbial-derived compounds, diet is known to influence gut microbiota composition and immunological, neurological, and hormonal functions.

Major components of the Western diet

The Western diet contains a high amount of saturated fat, refined carbohydrates, salt, sugar, and food additives associated with many health adversities.  

Fat

Fat is a calorie-rich food component with three subtypes, including unsaturated, trans, and saturated fats. While unsaturated fat is associated with many health benefits, trans and saturated fats increase the risk of various health complications. The Western diet contains many processed foods rich in trans and saturated fats.  

Studies conducted on healthy adult individuals have described that consuming a high-fat diet for 6 months causes significant alteration in gut microbiota composition, leading to reduced short-chain fatty acids and increased production of secondary bile acids. Moreover, a high-fat diet increases pro-inflammatory genes in the gut microbiota, leading to mild systemic inflammation.

Animal studies have shown that high-fat diet-induced changes in gut microbiota result in reduced mucosal immune response, increased pro-tumor immune response, and increased proliferation of gut epithelial cells and stem cells. All these factors collectively increase the risk of intestinal cancer development and progression.

High-fat diet-induced accumulation of Gram-positive bacteria in the liver, together with dysregulated bile acid metabolism, can lead to the induction of senescence-associated secretory phenotype in liver cells. These events are collectively responsible for liver cancer development.

High-fat diet-induced changes in microbiota can increase the biosynthesis and systemic levels of lipopolysaccharides, leading to an increased risk of breast, prostate, and esophageal cancers. 

Dietary fiber

Dietary fiber is a semi-digestible plant-based food component that helps in digestion and excretion. Microbiota-mediated partial fermentation and breakdown of dietary fibers in the intestine lead to the generation of various short-chain fatty acids. The Western diet contains much less plant-derived dietary fibers; thus, following this dietary pattern can lead to reduced production of beneficial microbial metabolites. 

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