Regulation of Lipid Metabolism in The Intestinal Flora

Trillions of microorganisms live in the gastrointestinal tract, far outnumbering the body's own cells. The intestinal flora is involved in many physiological and pathological processes in the host, including digestion and absorption of food, metabolism of certain nutrients and pharmaceutical compounds, development of host immunity, intestinal inflammatory states, and more. Dysbiosis of the intestinal flora is associated with a variety of human metabolic diseases, such as obesity, diabetes mellitus, and nonalcoholic fatty liver disease.

Schematic illustration of some of the many phenotypes and diseases where gut microbe involvement is reported (Allayee et al., 2015).

Regulation of lipoprotein metabolism by intestinal flora

The intestine is not only a site of lipid digestion and absorption, but also a place where a large number of microorganisms reside. The intestinal microbes are able to regulate dietary lipid composition, digestion and absorption and may alter the formation of intestinal lipoproteins.

Studies have shown abnormal lipoprotein levels in germ-free mice and in mice treated with antibiotics to remove intestinal flora. When fed a high-fat diet, germ-free mice were resistant to the obesity phenotype, while germ-free mice had lower plasma triglyceride and low-density lipoprotein levels compared to mice with normal flora, due in part to reduced lipid digestion, absorption and transport. In addition, supplementation of conventionally reared mice with specific bacterial strains resulted in increased body weight, elevated LDL and cholesterol levels, and altered expression of some genes involved in lipid transport. Fasting triglyceride levels and very-low-density lipoprotein production were significantly lower in germ-free mice compared to conventionally fed mice.

Intestinal flora and lipid profile

Many human studies have shown an association between intestinal flora and lipid profiles.

In humans, individuals with lower gut bacterial gene abundance had a significantly higher frequency of insulin resistance, higher fasting serum triglyceride levels, and higher LDL cholesterol levels. Another study found that individuals with lower Intestinal bacterial gene abundance had higher serum leptin, triglyceride, and free fatty acid levels, and lower serum lipocalin and HDL cholesterol levels.

Intestinal bacterial abundance was also negatively associated with height body mass index (BMI) and triglyceride levels and positively associated with HDL levels.

Patients with hypercholesterolemia had significantly higher serum total cholesterol, triglyceride and LDL cholesterol levels than healthy individuals, but significantly lower abundance and diversity of intestinal flora.

Dietary interventions can significantly dysbiosis the intestinal flora and increase the levels of mucinophilic Acinetobacter and Proteus mirabilis. Thus, dietary interventions may improve symptoms in patients with metabolic syndrome by modulating intestinal flora.

Regulation of host lipid metabolism by intestinal flora

• Intestinal flora affects bile acid composition and bile acid receptor signaling

The intestinal flora controls the homeostasis of bile acids and thus affects various host pathophysiological processes. Alterations in the intestinal flora not only affect the composition of bile acids, but also affect the bile acid receptor signaling pathway, which in turn plays a key role in the regulation of lipid metabolism. Bile acids are also bacteriotoxic and can affect the growth rate of certain bacteria and alter the levels of genes associated with intestinal bacteria involved in lipid and amino acid metabolism.

• Intestinal flora affects the level of metabolically produced short-chain fatty acids

Short-chain fatty acids are produced by intestinal bacteria fermenting indigestible carbohydrates. Intestinal short-chain fatty acids are dominated by acetic acid, propionic acid and butyric acid, which account for more than 95% of the short-chain fatty acid content. Short-chain fatty acids can be absorbed by the cecum, colon and rectum, then enter the mesenteric vein and finally enter the blood circulation. After entering the blood circulation, short-chain fatty acids can affect the metabolism of many peripheral tissues such as liver, adipose tissue and skeletal muscle.

• Intestinal flora affects the hormone secretion that regulates intestinal endocrine cells

Intestinal flora can regulate the development and function of enteroendocrine cells. Enteroendocrine cells have an apical membrane facing the intestinal lumen that allows them to interact with microorganisms and their metabolites. The intestinal flora and its metabolites can modulate the function of enteroendocrine L-cells, thus altering their ability to release hormones, as well as the actions of other enteroendocrine cells, such as intestinal chromophores.

• Intestinal flora regulates intestinal barrier function

The intestinal mucosal barrier not only helps to absorb water and essential nutrients, but also prevents the entry of harmful substances. The intestinal epithelial layer consists of absorptive intestinal epithelial cells, cup cells, enteroendocrine cells, tufted cells and panniculocytes. Substances can pass through this barrier by selective transport or simple diffusion (transcytosis pathway), or they can cross through the gaps between epithelial cells (paracellular pathway).

Lipopolysaccharides (LPS) are cell wall components of Gram-negative bacteria, also called endotoxins, which are normally confined to the intestinal lumen and are unable to cross the intestinal barrier, but when the intestinal barrier is weakened and an intestinal leak forms, endotoxins can enter the circulation and cause systemic inflammation. Elevated concentrations of LPS in the circulation can also increase the risk of atherosclerosis.

Reference

1. Allayee, H., & Hazen, S. L. (2015). Contribution of gut bacteria to lipid levels: another metabolic role for microbes?.

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