Does Gut Microbiota Fuel Metabolic Inflammation and Dysregulation?

November 28, 2019

Given that obesity and associated disorder type II diabetes mellitus have reached epidemic proportions worldwide, the development of efficient prevention and therapeutic interventions is a global public health interest. There is now a large body of evidence suggesting that the micro-organisms colonizing the human gut, known as gut microbiota, play a central role in human physiology and metabolism. Understanding how gut microbiota affects and regulates key metabolic functions such as glucose regulation and insulin resistance is an important health issue. We will highlight how prebiotic/probiotic interventions affect these bacterial processes and are now considered as promising approaches to treat obese and diabetic patients.

1. The gut microbiota of an obese person…

Obesity is a chronic, complex, and multifactorial disease representing the fifth leading cause of death in the world and accounting for almost 3.4 million deaths each year. Low-grade inflammation is the hallmark of metabolic disorders such as obesity, type 2 diabetes and nonalcoholic fatty liver disease.

Microbiota is now recognized as a real functional “organ” due to its immense impact on human health and has become the subject of intensive research over recent years. The vast majority of microbes reside in the intestinal tract, where they influence host physiology by playing fundamentally important roles in digestion, nutrition, immune regulation, and metabolism.

Gut microbiota composition and activity can fluctuate over time and depend on different factors including genetics, sex, age, health status, and drug/antibiotic consumption. Over the last decade, a large number of publications have reported a prominent role of microbiota in metabolic diseases.

Notably, accumulated evidence suggests an association between a dysregulated gut microbiome and obesity, glycemic control impairment, and therefore T2DM pathophysiology.

2. Obesity, Diabetes, and Dysbiosis

The preservation a normal and healthy gut microbiota plays a critical role in maintaining good health. Alterations of both composition and function of the microbiota, termed dysbiosis, are common features of several pathologies including metabolic diseases such as obesity and T2DM.

A number of preclinical and clinical studies have attempted to describe the differences between gut microbiota in obese, compared to lean individuals and have reported that obesity is related to lower microbial diversity and greater depletion. In early obesity, microbiota studies report that an increase of body weight is associated with a microbiota shift.

Although T2DM is generally considered as an attribute to obesity, some studies have correlated glycemic control impairment and insulin resistance to specific gut microbiota composition. Furthermore, antidiabetic drugs liraglutide and metformin have been recently shown to significantly lower body weight and improve glucose metabolism while considerably modifying the composition of gut microbiota.

Liraglutide decreased obesity-related microbial phenotypes and increased lean-related phenotypes while metformin modifies the intestinal microbiota composition by inducing the growth of several bacteria.

There is proof that gut microbiota is involved in the beneficial glucose-lowering effects of antidiabetic agents and that it is a promising therapeutic target in T2DM and the glycemic control impairment context.

3. How can Gut Microbiota be moderated?

Through several mechanisms, gut bacteria influence the chronic low grade inflammation that culminates in insulin resistance and the increase in fat deposits and body weight gain, characteristic of obese individuals.

With the acknowledgement of these obesity and inflammation induction mechanisms, several strategies to block or attenuate them are being developed and tested, in order to benefit obese and type 2 diabetic patients. We will look at these mechanisms and the effect they have:

3.1. Antibiotic Therapy

The use of broad spectrum antibiotic therapy greatly modifies the gut microbiota profile although the prevalence of surviving bacteria and the benefits for the host have not been determined, as the concept of a “healthy” gut microbiota is still under investigation.

The main mechanism suggested by antibiotic administration is a reduction in circulating LPS levels, which lessens inflammation and improves the insulin resistance induced by obesity in the liver, muscle, and adipose tissue. Improved intestinal function has also been noted as a benefit of the administration of antibiotics.

However, even with this striking metabolic improvement in antibiotic therapy experiments, it seems that translating this strategy to humans is not the best option, as there are complex issues such as antibiotic resistance in chronic administration panels and evidence that indicates a relationship between chronic low-dose antibiotic therapy and body weight gain.

3.2. Probiotics

Probiotics are live microorganisms that can be consumed through fermented foods or supplements. More and more studies show that the balance or imbalance of bacteria in your digestive system is linked to overall health and disease. Probiotics promote a healthy balance of gut bacteria and have been linked to a wide range of health benefits.

As obesity is a key cause of diabetes, probiotics can help with weight loss through a number of different mechanisms. An example is that some probiotics prevent the absorption of dietary fat in the intestine.The fat is then excreted through feces rather than stored in the body. Probiotics may also help you feel fuller for longer, burn more calories and store less fat. This is partly caused by increasing levels of certain hormones, such as GLP-1.

Probiotics may also help with weight loss directly. In one study, dieting women who took Lactobacillus rhamnosus for 3 months lost 50% more weight than women who didn’t take a probiotic. Another study of 210 people found that taking even low doses of Lactobacillus gasseri for 12 weeks resulted in an 8.5%.

It is however important to note that not all probiotics aid in weight loss. Some studies have found certain probiotics, such as Lactobacillus acidophilus, can even lead to weight gain.

3.3. Prebiotics

Prebiotics are classified as the non-digestible food ingredients that probiotics can feed off. They are used in the gut to increase populations of healthy bacteria, aid digestion and enhance the production of valuable vitamins. Galactooligosaccharides (GOS) are the most advanced form of prebiotics which belong to a group of particular nutrient fibers that feed and encourage the growth of good bacteria in the gut.

The major source of prebiotics is dietary fibre. They occur naturally in fruits and vegetables, but you can also take them in the form of nutritional supplements.

3.4. Bariatric Surgery

Bariatric surgery is an important method in the treatment of obesity. It is quite effective in achieving and protecting weight loss. This effectiveness of obesity treatment after bariatric surgery is not only related to food consumption. The altered microbiota after bariatric surgery has an impact on its effectiveness. Malabsorption status after bariatric surgery, changes in the metabolism of bile acids, changes in gastric pH, and changes in the metabolism of hormones lead to gut microbiota changes. Changes in microbiota also affect energy homeostasis. Because of these reasons, body weight loss is achieved after bariatric surgery.

4. What role will gut microbiota play in the treatment of T2DM in the future?

It is becoming increasingly clear that gut microbiota has profound impact on general health and well-being. Notably, it is now well-established that imbalanced gut microbiota is linked to host glycemic control impairment and T2DM development. Although the precise role of gut microbiota remains incompletely understood, further investigation is likely to be very helpful in the treatment and control of obesity, and resultant Type 2 Diabetes.

Current treatments of this complex chronic disease are far from being ideal since in a majority of patients, T2DM remains poorly controlled in the long run. Using pre/probiotics to control blood glucose has been considered for a long time, and the discovery of the key roles of gut bacteria in T2DM has boosted research efforts in this field.

A better understanding of how gut microbiota impacts general health will help in outlining new treatment strategies. These strategies will help in identifying probiotic strains with antidiabetic activities, or nutritional interventions that can increase helpful microbiota in the gut.

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