Diabetes Metab J.  2020 Oct;44(5):658-667. 10.4093/dmj.2019.0220.

Revisiting the Bacterial Phylum Composition in Metabolic Diseases Focused on Host Energy Metabolism

• Lee Y
• Lee HY

• KMID: 2513027
• DOI: http://doi.org/10.4093/dmj.2019.0220

Abstract

Over a hundred billion bacteria are found in human intestines. This has emerged as an environmental factor in metabolic diseases, such as obesity and related diseases. The majority of these bacteria belong to two dominant phyla, Bacteroidetes and Firmicutes. Since the ratio of Firmicutes to Bacteroidetes increases in people with obesity and in various animal models, it has been assumed that phylum composition causes the increase in occurrence of metabolic diseases over the past decade. However, this assumption has been challenged by recent studies that have found even an opposite association of phylum composition within metabolic diseases. Moreover, the gut microbiota affects host energy metabolism in various ways including production of metabolites and interaction with host intestinal cells to regulate signaling pathways that affect energy metabolism. However, the direct effect of gut bacteria on host energy intake, such as energy consumption by the bacteria itself and its effects on intestinal energy absorption, has been underestimated. This review aims to discuss whether increased ratio of Firmicutes to Bacteroidetes is associated with the development of metabolic diseases, and whether energy competition between the bacteria and host is a missing part of the mechanism linking gut microbiota to metabolic diseases.

Keyword

Energy metabolism; Etiology; Gastrointestinal microbiome; Intestinal absorption; Metabolic diseases

Figure

• 

  Fig. 1 Gut microbiota contribute to host energy absorption through the direct/indirect ways. Food intake alters the composition of the gut microbiota and the gut microbiota influences host energy absorption directly or indirectly while the nutrients are traveling in the intestine. The nutrients, which are obtained from a meal, undergo one of three routes during the digestive processes in the intestine, in face of energy metabolism, or the remains of them are excreted from the body. First, the nutrients such as carbohydrates, proteins, and lipids are digested and degraded with digestive enzymes and then absorbed into the host. Second, gut microbiota directly consume nutrients as their energy source. Lastly, the nutrients can be converted into metabolites such as short-chain fatty acids (SCFAs; acetate, butyrate, and propionate), trimethylamine N-oxide (TMAO), and indole propionate (IPA) by the gut microbiota. The gut microbiota producing metabolites are absorbed and circulated in the host. Acetate reduces the fat accumulation by stimulating the AMPK-peroxisome proliferator-activated receptor α (PPARα) pathway and G-protein-coupled receptor 43 (GPR43) in the liver and white adipose tissue (WAT), respectively [3738]. Butyrate induces intestinal gluconeogenesis (IGN) via cAMP signal and decreases hepatic fat accumulation by GPR43 and releases phosphorylated hormone-sensitive lipase (p-HSL) by adrenergic β3 receptor (ARβ3). Moreover, butyrate activates thermogenesis in brown adipose tissue (BAT) and transformation to oxidative fibers in the skeletal muscle via the AMPK-peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) pathway. Propionate, a precursor of glucose in tissues, stimulates IGN and hepatic gluconeogenesis. Gastrointestinal microbiome-producing SCFAs release gut hormones (glucagon like peptide-1 [GLP-1], peptide YY [PYY], cholecystokinin [CCK]) from enteroendocrine cells by stimulating GPR43. The gut hormones regulate appetite and satiety. Besides producing SCFAs, the gut microbiota can also produce TMAO, which is a major risk factor of cardiovascular disease. The IPA, which is produced from tryptophan by the gastrointestinal microbiome, improves insulin secretion. Lipopolysaccharide (LPS), produced by gram-negative bacteria, promote metabolic disease thought induction of inflammation as an endotoxin. Succinate, which fermented from dietary fiber by gut bacteria, activates IGN, resulting improving metabolic disease such as glucose homeostasis. Additionally, gut microbiota can convert primary bile acids into secondary bile acids in the intestine. The bile acids bind G protein-coupled bile acid receptor 1 (TGR5) upon the enteroendocrine cell and function as farnesoid X receptor (FXR) agonist. FFA, free fatty acid; AA, amino acid.

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