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Does gut microbiota fuel metabolic inflammation and dysregulation?

Important Points:

  • Probiotics
  • Microbiota
  • Diabetes
  • Antibiotics
  • Prebiotics

Does gut microbiota fuel metabolic inflammation and dysregulation?

Given that obesity and the 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. Obesity, Diabetes, and Dysbiosis

Obesity is a chronic, complex, and multifactorial disease representing the fifth leading cause of death in the world 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 is affected by 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 Type 2 Diabetes pathophysiology.

The preservation of 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 Type 2 Diabetes.

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

Although Type 2 Diabetes is generally attributed 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 Type 2 Diabetes and any glycemic control impairment context.

2. How can Gut Microbiota be moderated?

Through several mechanisms, gut bacteria influenced 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. Here are a few of these mechanisms and their effects:

2.1. 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.

2.2. 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 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% loss.

It is 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.

2.3. 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 fiber occurring naturally in fruits and vegetables, but you can also take them in the form of nutritional supplements.

2.4. 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 too. Malabsorption status after bariatric surgery, changes in the metabolism of bile acids, changes in gastric pH, and changes in the metabolism of hormones all lead to gut microbiota changes. Changes in microbiota also affect energy homeostasis. Because of these reasons, body weight loss is achieved after bariatric surgery.

  • What role will gut microbiota play in the treatment of Type 2 Diabetes in the future?

It is becoming increasingly clear that gut microbiota has profound impact on general health and well-being. It is now well-established that imbalanced gut microbiota is linked to host glycemic control impairment and Type 2 Diabetes 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, Type 2 Diabetes 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 Type 2 Diabetes 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.

References:

  1. Hindawi (2013): Influence of Gut Microbiota on Subclinical Inflammation and Insulin Resistance. Retrieved from https://www.hindawi.com/journals/mi/2013/986734/
  2. Frontiers in Endrocrinology (2019): Impact of Gut Microbiota on Host Glycemic Control. Retrieved from

https://www.frontiersin.org/articles/10.3389/fendo.2019.00029/full

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Are antibiotics more harmful when given earlier in life?

Table of Contents:

  • Antibiotics
  • Vaccination
  • Microbes
  • Sanitatize

Are antibiotics more harmful when given earlier in life?

If you were asked whether babies and germs should be mixed, you would probably answer by reflex with a resounding no. These two life forms are not exactly meant to go hand and hand, at least in a traditional sense. Yet, this exact concept is what the book “Let Them Eat Dirt: Saving Your Child from an Oversanitized World” is trying to challenge. Written by doctors Brett Finlay and Marie-Claire Arrieta, this book takes a controversial stand against the over sanitation of the baby’s environment.

Until recently, it has been the norm that a baby’s environment should be as clean as possible. To quote the book, the belief was “the only good microbe is a dead one.” It is undeniable that we are now here today because of the milestones in medicine that aimed to control microbes which include vaccines, sterilization, pasteurization of food, and antibiotics, but with today’s emerging slew of autoimmune diseases, it has become clearer that this old time tested strategy might not work anymore.

In the book, the authors cite the phenomenon in which countries that have a tendency to over sanitize have significantly higher rates of non-infectious diseases like asthma, diabetes, and autoimmune conditions. While those who are located in environments that have a richer microbial profile tend to report lower numbers of these diseases.

To support this position, the authors pointed out an article published by Dr. David Strachan almost 25 years earlier.  In the article, Dr.Strachan states that the absence of exposure to bacteria in early childhood contributed to the development of allergies, and that without bacterial exposure, our immune system will not fully mature. These propositions would later become known as the hygiene hypothesis.

With the recent emergence of studies supporting the hygiene hypothesis, the authors of the book enumerated the possible culprits in hindering the development of the immune system.

One culprit is the misuse of antibiotics. It is stressed in the book that antibiotics are truly lifesavers. In the past, 90 percent of children would eventually die due to bacterial meningitis, but now a full recovery is the standard. Sadly, the world is experiencing a trend in antibiotic overuse. It has been estimated that between 2000 and 2010, the use of antibiotics has increased by 36 percent worldwide. Even more alarming is that the use increases during flu season where the drugs are virtually useless because influenza is caused by viruses which do not respond to antibiotics. The true harm is not that it is useless but the damage it causes to the normal flora.

Even if we use antibiotics properly for the correct indications, there is still the problem of antibiotics used in our food. Antibiotics are widely used as supplements given to livestock which increase the meat yield. This practice has been banned in Europe but is still in action here in the United States. Parallel to the growth induced in animals, antibiotics seem to have a similar effect in children. According to the CDC, the states with the highest rates of antibiotic usage also have higher rates associated with obesity.

At first, this was just a matter of statistics but after recreating the observation in the lab, the concern is definitely valid. When mice with sterile guts were given bacteria from obese mice, the test subjects became obese too. This further supports the notion that bacterial composition affects weight gain.

The effect does not end with weight alone. It would appear even allergies are deeply rooted in the way bacterial flora is set up. In a study published in the British Medical Journal, it was shown that antibiotic exposure during early life was associated with an increased likelihood of developing asthma in the future, but remarkably, antibiotics given later in life did not produce the same effect. This brings into light that timing is also an important factor to consider when talking about antibiotics. One thing remains clear: modifying the bacteria in our body has a greater impact than we first thought.

The importance of antibiotics in our survival over the past hundreds of years cannot be stated enough. What books like these are urging is not to discredit antibiotics but to revolutionize the way we look act microbes. Over the past decades, it seems like the focus of making antibiotics is to increase its strength not to mention the profitability through its widespread use. What the authors of Let Them Eat Dirt are wisely asking us is to be respectful of our body’s natural defenses and to harness its full potential through the judicious use of medications.

Let Them Eat Dirt: Saving Your Child from an Oversanitized World

https://www.amazon.com/Let-Them-Eat-Dirt-Oversanitized/dp/1616206497

Blaser Explores Link Between Obesity, Antibiotic Use

https://nihrecord.nih.gov/newsletters/2014/11_21_2014/story1.htm

Antibiotics in fetal and early life and subsequent childhood asthma: nationwide population-based study with sibling analysis

http://www.bmj.com/content/349/bmj.g6979