Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature

Table 1

Suggested mechanisms for the role of gut microbiota in the aetiology of obesity.

	Proposed mechanism	Mediators	Source of mediators	Target tissues/organs	Local/systemic effects
Metabolic	Increased production of short chain fatty acids [1]	Bacterial glycosyl hydrolases	Colon, distal ileum, and rectum	Colonic enterocytes	↑ energy harvest; Energy for colonocytes; Alteration in cholesterol metabolism
	Muscle fatty acid oxidation [1]	↓ AMP kinase	Small intestine	Muscle, liver	↓ muscle fatty acid oxidation
	Bile acid circulation [19]	Secondary bile acid production	Colon	Colon	Reverse cholesterol transport
	Expression of liver ChREBP/SREBP-1 [1]	↑ glucose absorption	Liver	Liver	↑ hepatic lipogenesis
Inflammatory	Chronic low-grade inflammation [9]	LPS, NF-kappaB, and TNF-α mRNA	Colon, ileum	Endothelium, hypothalamus?	Metabolic endotoxemia and hyperphagia
	↑ endocannabinoid (eCB) system tone [10, 20]	Bacterial LPS	Ileum, colon	Stomach, small and large intestine	↑ gut permeability and ↓ apelin and APJ mRNA expression
Hormonal	Suppression of Fiaf [1]	Colonic L-cells	Colon	Adipose tissue	↑ lipolysis, ↓ muscle fatty acids oxidation
	↑ PYY [21]	Satiety centre	Ileum, colon	Hypothalamus	↓ appetite, ↓ gastric motility, and ↓ gut emptying
	Expression of G protein coupled receptors 41 and 43 (GPR41 and GPR43) [22]	SCFA (acting as a ligand)	Colon, distal ileum, and rectum	Liver, brain	↑ peptide YY (PYY), ↑ de novo hepatic lipogenesis

AMP: adenosine monophosphate, ChREBP: carbohydrate response element binding protein, SREBP-1: sterol response element binding protein-1, PYY: peptide YY, LPS: lipopolysaccharide, NF-kappaB: nuclear factor-kappaB, TNF-α: tumour necrosis factor alpha, mRNA: messenger RNA, GPR41 and GPR43: G protein coupled receptors 41 and 43, SCFA: short chain fatty acid, and eCB: endocannabinoid.