Obesity, often a result of eating too much fat and sugar in combination with low physical activity, is known as a key factor for developing Type 2 diabetes. However, some obese people do not develop the disease that affect millions globally. Turns out their gut bacteria have a role to play. Andrey Morgun and Natalia Shulzhenko of Oregon State University and Giorgio Trinchieri of the National Cancer Institute developed a novel analytical technique, multi-organ network analysis, to explore the mechanisms behind early-stage systemic insulin resistance.
The findings, published in the Journal of Experimental Medicine, showed that a particular type of gut microbe leads to white adipose tissue containing macrophage cells, large cells that are part of the immune system, associated with insulin resistance. In the human body, white adipose tissue is the main type of fat.
"Our experiments and analysis predict that a high-fat/high-sugar diet primarily acts in white adipose tissue by driving microbiota-related damage to the energy synthesis process, leading to systemic insulin resistance," said Morgun, associate professor of pharmaceutical sciences in the OSU College of Pharmacy.
"Treatments that modify a patient's microbiota in ways that target insulin resistance in adipose tissue macrophage cells could be a new therapeutic strategy for Type 2 diabetes," he added. The human gut microbiome features more than 10 trillion microbial cells from about 1,000 different bacterial species.
"The so-called 'western diet', high in saturated fats and refined sugars, is one of the primary factors. But gut bacteria have an important role to play in mediating the effects of diet," Shulzhenko said. Experiments in mice, looking at the intestine, liver, muscle and white adipose tissue, the team found "adipose tissue has a predominant role in systemic insulin resistance".
Further they "discovered that the Oscillibacter microbe, enriched by a western diet, causes an increase of the insulin-resistant adipose tissue macrophage". The researchers add, however, that Oscillibacter is likely not the only microbial regulator for expression of the key gene they identified, Mmp12, and that the Mmp12 pathway, while clearly instrumental, is probably not the only important pathway, depending on which gut microbes are present. Previously studies have shown that another microbial species "Romboutsia ilealis worsens glucose tolerance by inhibiting insulin levels, which may be relevant to more advanced stages of Type 2 diabetes", Shulzhenko said.