The human gut microbiome and body metabolism: implications for obesity and diabetes

Abstract

Background: Obesity, metabolic syndrome, and type 2 diabetes are major public health challenges. Recently, interest has surged regarding the possible role of the intestinal microbiota as potential novel contributors to the increased prevalence of these 3 disorders.

Content: Recent advances in microbial DNA sequencing technologies have resulted in the widespread application of whole-genome sequencing technologies for metagenomic DNA analysis of complex ecosystems such as the human gut. Current evidence suggests that the gut microbiota affect nutrient acquisition, energy harvest, and a myriad of host metabolic pathways.

Conclusion: Advances in the Human Microbiome Project and human metagenomics research will lead the way toward a greater understanding of the importance and role of the gut microbiome in metabolic disorders such as obesity, metabolic syndrome, and diabetes.

Fig. 1. Hyperglycemia (HG) and increased free fatty acids (FFA), which are hallmarks of obesity, metabolic syndrome, and diabetes, combined with a high-fat, high–glycemic load diet, could result in increased activation of the inflammasome complex as well as increase the activation of macrophages via increased TLR activation and nuclear factor κB (NF-κB) activation

Increased metabolic endotoxemia may occur and activate the TLR4 pathway via the adapter protein, MyD88, leading to immune cell activation and inflammation. Also, macrophages could infiltrate the adipose tissue and activate mitogen-activated protein kinases, such as c-Jun aminoterminal kinase (JNK) and NF-κB, resulting in increased cross-talk and adipose-tissue–derived adipokines. A hyperglycemic and high fat diet could also result in changes to the gut microbiome by altering the content of histidine, glutamate, SCFAs, and other factors and promote gut-barrier dysfunction and conditions prevalent in obesity, metabolic syndrome, and diabetes by altering the host response. All of these metabolic alterations that result in increased systemic inflammation, macrophage activity, and TLR activation contribute to the increased cardiometabolic burden in obesity, diabetes, and metabolic syndrome.

Fig. 2. Intestinal microbes may play an important role in host-microbiota interactions via luminal conversion

Nutrients consumed by the host may be converted by intestinal microbes into several bioactive compounds that could affect the health and disease states of the host and the intestinal microbiota. SCFAs = short-chain fatty acids. Reproduced with permission from Hemarajata et al. (78).