Abstract
The human gut harbors more than 100 trillion microbial cells, which have an essential role in human metabolic regulation via their symbiotic interactions with the host. Altered gut microbial ecosystems have been associated with increased metabolic and immune disorders in animals and humans. Molecular interactions linking the gut microbiota with host energy metabolism, lipid accumulation, and immunity have also been identified. However, the exact mechanisms that link specific variations in the composition of the gut microbiota with the development of obesity and metabolic diseases in humans remain obscure owing to the complex etiology of these pathologies. In this review, we discuss current knowledge about the mechanistic interactions between the gut microbiota, host energy metabolism, and the host immune system in the context of obesity and metabolic disease, with a focus on the importance of the axis that links gut microbes and host metabolic inflammation. Finally, we discuss therapeutic approaches aimed at reshaping the gut microbial ecosystem to regulate obesity and related pathologies, as well as the challenges that remain in this area.
Highlights
The human gut harbors more than 100 trillion microbial cells, which have an essential role in human metabolic regulation via their symbiotic interactions with the host
Owing to the essential role of the gut ecosystem in maintaining host physiology, its alteration can trigger a wide range of physiological disorders, including low-grade inflammation, metabolic disorders, excess lipid accumulation, and loss of insulin sensitivity, which increase the risk of developing metabolic diseases
(See figure on previous page.) Fig. 3 Induction of inflammatory signals in proinflammatory macrophages and their connection with insulin pathways. a After translocation of gut bacteria to other tissues, the bacterial lipopolysaccharides (LPS) in the circulation and organs activate the transcription of cytokines via Toll-like receptor (TLR)4
Summary
Link between impaired insulin action, low-grade inflammation, and obesity In healthy individuals, insulin triggers glucose uptake in peripheral organs and the secretion of this hormone is activated by the rise in postprandial plasma glucose concentration. Loss of insulin sensitivity triggers fasting hyperglycemia and increases hepatic lipid synthesis, dyslipidemia, hypertension, and fat accumulation in adipose tissues. Excessive calorie intake, increased fat accumulation, and lipotoxicity activate the production of effector molecules (cytokines) and cells that are primarily involved in innate immunity [23, 24]. Fecal microbiota transplanted from conventionally raised mice to germfree mice triggered a 57 % increase in the amount of body fat and a dramatic increase in hepatic triglyceride levels and insulin resistance without modifying the amount of food consumed [11]. The expression of host genes involved in energy homeostasis, lipid metabolism, and mitochondrial metabolism in different parts of the gut, as well as in the liver and adipose tissues, is markedly different in germ-free mice and conventionally raised mice [35]. Affect digestive tract physiology Change gut motility Increased energy harvest
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