Linking Gut Microbiome and Lipid Metabolism: Moving beyond Associations

Abstract

Various studies aiming to elucidate the role of the gut microbiome-metabolome co-axis in health and disease have primarily focused on water-soluble polar metabolites, whilst non-polar microbial lipids have received less attention. The concept of microbiota-dependent lipid biotransformation is over a century old. However, only recently, several studies have shown how microbial lipids alter intestinal and circulating lipid concentrations in the host, thus impacting human lipid homeostasis. There is emerging evidence that gut microbial communities play a particularly significant role in the regulation of host cholesterol and sphingolipid homeostasis. Here, we review and discuss recent research focusing on microbe-host-lipid co-metabolism. We also discuss the interplay of human gut microbiota and molecular lipids entering host systemic circulation, and its role in health and disease.

Keywords: gut; lipidomics; lipids; metabolomics; microbiome.

Figure 1

Transformation of dietary sphinganine into dihydrocermides by the gut microbes. Here, sphinganine alkyne (SAA) was given to mice by oral gavage (five consecutive days), then the fecal content from mice was collected and metabolic consequences of SAA exposure were determined using high-resolution mass spectrometry ion chromatograms. The authors showed a distinct cecal lipidome chromatograms for mice that orally treated with SAA (blue), which contained the alkyne-bearing (A) C15-, (B) C15OH-, (C) C16OH-, (D) C17OH-, (E) C18:2- and (F) C22:2- dihydrocermides. However, these dihydrocermides were absent in treatments with sphinganine (SA, green), vehicle or no treatment (red). Figure adapted from [40], with permission under CC BY 4.0 license.

Figure 2

The metabolism of cholesterol by gut microbes influences both intestinal and circulating cholesterol concentrations. (A) The cholesterol level in the blood can be influenced either by de novo cholesterol synthesized in the liver or it may be derived from exogenous sources such as the diet. The endogenous cholesterol level may be also influenced by drugs such as statins, or via altered bile acid metabolism. In addition, gut microbial metabolism of cholesterol may also serve as check point for the maintenance of cholesterol homeostasis (B). As shown in panel A, the authors proposed a pathway for microbial conversion of cholesterol (1) to coprostanol (4) in the microbiota involves the intermediates cholestenone (2) and coprostanone (3). (C) By using genome mining, Kenny et al. identified and characterized microbial enzymes linked with cholesterol metabolism. Later, integrating the functional metagenomics and metabolomics data, they predicted as well as validated a group of microbes and their microbial activities (microbial cholesterol dehydrogenases) which mediated the metabolism of cholesterol in the gut (D). Figure adapted from [52] with permission under CC BY 4.0 license.