01/21/2014

Story Source

Brett Moskowitz, MA
Reviewed By Clifton Jackness, MD, Attending Physician in Endocrinology and Internal Medicine, Lenox Hill Hospital and the Mount Sinai Medical Center, New York, NY

Take Note

• The relationship between gut microbiota and type 2 diabetes risk is under investigation.
• Accumulating evidence suggests that it is important to characterize the ways in which changing the gut microbiota might someday be a therapeutic target for patients with type 2 diabetes.

Image from MedPageToday.com

Numerous risk factors contribute to type 2 diabetes, including age, family history, diet, sedentary lifestyle, and obesity. Now, emerging research is examining how gut microbiota may contribute to type 2 diabetes risk. Gut microbiota densely populate the digestive tract, playing a crucial role in the normal structure and development of a healthy mucosal immune system and affecting uptake of nutrients, regulation of metabolism, angiogenesis, and development of the enteric nervous system.^1,2Intestinal microflora are a healthy and beneficial asset, but some components can become a liability if they are associated with a genetic susceptibility to certain illnesses. In these circumstances, microflora can contribute to the pathogenesis of various intestinal disorders and have a systemic impact on inflammation, for example.

A specific metabolic state combined with certain gut microbiota may facilitate low-grade systemic inflammation if gram-negative bacterial fragments (endotoxins) are able to cross the intestinal mucosa to enter the circulation.¹Patients with type 2 diabetes are particularly susceptible to increased endotoxin circulation associated with abnormal dietary changes.¹ In fact, some experts advocate for the normalization of gut microflora through dietary changes.¹

Studies have already linked red meat consumption to the development of diabetes. But recent findings in other disease areas have increased interest in the potential link between the gut microbiota and type 2 diabetes. While previous studies have shown that regular consumption of red meat is associated with shorter life expectancy, a large study recently suggested a relationship between the functions of gut microbiota after red meat consumption and an increased risk of cardiovascular disease and cardiac events.³ The findings support the theory that the gut microbiota may play a major role in metabolic diseases.

The investigators found that compared to vegans or vegetarians, patients whose diets included red meat—which is rich in L-carnitine (a trimethylamine)—produced more trimethylamine-N-oxide (TMAO). TMAO is produced from L-carnitine in the human gut by intestinal microbiota and is known to speed atherosclerosis in rodents. In this study, the level of L-carnitine in almost 2600 meat-eating subjects undergoing cardiac evaluation predicted increased risks for cardiovascular disease and myocardial infarction, stroke, or death, but only among subjects who also had high TMAO levels.³ This finding raised the possibility that gut microbiota may explain at least some of the association between red meat consumption and cardiovascular risk.

How do studies like this one apply to the management of patients with type 2 diabetes? The answer is not clear, but smaller studies have already shown that type 2 diabetes in humans is associated with a different composition of intestinal microbiota compared to nondiabetic persons, changes that are manifested primarily at the phylum and class level.⁴ One group of investigators studied the intestinal microbiota of 36 men with a range of body-mass indices (BMIs), half of whom had type 2 diabetes. Compared to the control group, fecal proportions of phylum Firmicutes and class Clostridia were significantly reduced among subjects with diabetes. Ratios of Bacteroidetes to Firmicutes and ratios of Bacteroides-Prevotellagroup to C coccoides-E rectale group were significantly and positively correlated with plasma glucose levels but not BMI. In addition, class Betaproteobacteria was highly enriched in diabetic compared to nondiabetic persons and positively correlated with plasma glucose.⁴

Advances like these have led to considerable anticipation among researchers about what is to come. “These are exciting times from a research perspective,” says Stanley L. Hazen, MD, PhD, a co-author on the L-carnitine study and chair of the Department of Cellular and Molecular Medicine; section head, Preventive Cardiology and Rehabilitation; and vice chair of translational research, Lerner Research Institute at the Cleveland Clinic. “I never imagined 5 years ago there was a mechanistic link between gut microbes and both cardiovascular disease and type 2 diabetes.”

At least one study is underway to evaluate the use of probiotics to reduce endotoxin levels and inflammatory responses in patients with type 2 diabetes. The investigators hypothesize that prebiotics/probiotics will offer an additional intervention to treat these patients.

In light of findings that intestinal microbiota may differ between patient populations with different metabolic abnormalities, future research will need to find targeted therapeutic strategies for these different patient populations. “We are many steps closer to the next major advances in powerful new diagnostic tests and therapeutic interventions for the prevention and treatment of cardiometabolic diseases,” says Dr. Hazen. “But it is still too early to turn this information into actionable changes in how we care for our patients.”

Published: 01/21/2014

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