J Obes Metab Syndr.  2017 Jun;26(2):86-96. 10.7570/jomes.2017.26.2.86.

The Roles of the Gut Microbiota and Toll-like Receptors in Obesity and Nonalcoholic Fatty Liver Disease

Affiliations
  • 1Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan. miura116@doc.med.akita-u.ac.jp

Abstract

Obesity is characterized by low-grade chronic inflammation and is closely associated with the cardiovascular diseases, diabetes, and nonalcoholic fatty liver disease. Emerging data demonstrate that the gut microbiota contributes to the development of obesity by regulating the innate immune system, including the Toll-like receptors (TLRs): an altered gut microbiota composition and elevated TLR ligands are observed in obese mice and humans. The changes in the gut microbiota include an increased abundance of Firmicutes phylum and a decreased abundance of Bacteroidetes phylum. The population of beneficial bacteria that function as probiotics is decreased whereas harmful bacteria that can produce lipopolysaccharide, a TLR4 ligand, are increased in the obese state. In addition, the gut permeability is increased in obesity, which allows the delivery of larger amounts of bacterial components to the liver through the portal vein. Immune cells recognize these bacterial components through TLRs and produce diverse cytokines that kill invading pathogens. However, the sustained activation of TLR signaling induces host damage due to chronic exposure to harmful cytokines, which are produced from TLR expressing cells, including monocytes/macrophages. In the obese state, the expression of TLR is increased in several organs, including the adipose tissue and the liver. At the cell level, negative regulators of TLR signaling are suppressed, leading to activation of TLR signaling. These alterations promote inflammation in many organs. Thus, the gut microbiota and TLR signaling are therapeutic targets in patients with obesity and its related diseases.

Keyword

Obesity; Nonalcoholic fatty liver disease; Gut microbiota; Toll-like receptor
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