Microbiota & Its Role in Obesity and Diabetes

Obesity has more than doubled globally since 1980.

Positive energy balance (ingesting more energy than expended).

Obesity significantly increases the risk of type 2 diabetes.

Approximately 422 million adults globally had diabetes in 2014.

High blood sugar, insulin resistance, and relative lack of insulin.

Insulin resistance increases free fatty acid levels, affecting blood lipids.

High triglycerides, low HDL, and high small dense LDL in diabetes.

Dyslipidaemia is a major risk factor for heart disease in people with diabetes.

A cluster of health problems involving abnormal glucose and lipid metabolism, defined by abdominal obesity and at least two of the following: high triglycerides, low HDL cholesterol, high blood pressure, and increased fasting blood sugar.

The gut microbiota plays a significant role in regulating fat storage. Studies in mice demonstrate that the altered microbiota found in obese mice can transfer obesity to lean mice via microbiota transplantation.

The gut microbiota is deeply intertwined with insulin resistance and diabetes. Changes in the gut microbiome have been linked to both positive and negative effects on diabetes development.

LPS is a component of bacterial cell walls that triggers low-grade inflammation and insulin resistance by binding to Toll-like receptor 4.

Bile acids, modified by gut microbes, play a crucial role in controlling diabetes. They activate receptors that regulate glucose metabolism and insulin sensitivity.

SCFAs, produced by gut bacteria, enhance insulin sensitivity. They activate L cells in the gut to release GLP-1, a hormone that improves glucose control.

FMT involves transferring healthy gut bacteria from a donor to a recipient, aimed at restoring healthy gut microbiome function. This is a promising therapeutic intervention for diabetes.

Metformin, a common diabetes medication, alters the gut microbiota. Probiotics, live bacteria supplements, can also potentially improve gut health and diabetes management.

Symbiosis is a harmonious relationship between bacteria and the host. Dysbiosis occurs when this balance is disrupted, leading to harmful bacteria (pathobionts) and potential disease.

The gut microbiome plays a significant role in cancer development. Dysbiosis, inflammation, and microbial metabolism products can contribute to tumor growth.

Dysbiosis leads to increased inflammation, triggering cytokine and chemokine production. These chemicals promote cell proliferation and suppress cell death.

The food we eat affects both the composition of our gut bacteria and our risk of cancer. Microbial metabolism products can contribute to tumor development.

Five dominant phyla are found in the stomach: Firmicutes, Bacteroides, Actinobacteri, Fusobacterium, and Proteobacteri. H. pylori infection and prolonged PPI use can change the microbiota and increase cancer risk.

A thick mucus layer protects the colon lining from bacteria and food antigens. The ratio of anaerobic to aerobic bacteria is different at the mucosal surface compared to the gut lumen.

Rats share a similar gut microbiota with humans, making them valuable for studying the role of the microbiome in human health and diseases.

The link between the gut microbiome and cancer is complex. Dysbiosis, bacterial metabolism, inflammation, and dietary factors all play a role.

Certain types of bacteria, like Streptococcus bovis, have been observed in a high percentage of colorectal cancer patients, suggesting a potential connection.

Higher levels of Bacteroides and Prevotella bacteria in the colon are often associated with increased levels of IL-17 immune cells in tumor samples, a potential indicator of inflammation.

The liver itself doesn't have a unique microbiota, but it's indirectly impacted by gut bacteria through the portal vein, leading to exposure to various antigens and bacterial byproducts.

Obesity can disrupt the gut's microflora, increasing the production of deoxycholic acid (DCA), a secondary bile acid, by Clostridia, which is linked to an increased risk of liver cancer.

Antibiotics can help by reducing LPS and TLR4, while probiotics can reduce LPS and the toxicity of aflatoxin, beneficial for liver health.

Certain probiotics like Bifidobacterium breve and Lactobacillus rhamnosus have been observed to reduce pro-inflammatory cytokine production and DNA methylation in the host.

Factors like smoking, age, obesity, diet, genetics, and the immune system can contribute to colon cancer, particularly through damage caused by harmful substances from gut bacteria.

The interactions between gut bacteria and dietary components can produce harmful substances, like secondary bile acids, that play a crucial role in cancer development.