The Human Microbiome in Overweight and Obesity: The Dawn of a New Era?

Evolution-of-ObesityAlthough some health practitioners still cling to the idea that weight management is all about calories in vs. calories out, the scientific literature shows that several other factors are essential to the development and progression of overweight and obesity. The microorganisms that live in and on our body (the human microbiome) have long been a blind spot in obesity research, but recent studies showing that the state of this microbiome largely determine if we are lean or overweight, are now changing our perspective on obesity, diabetes, and insulin resistance. It’s clear that we no longer should just consider the human part of our body (10% of cells), but that the trillions of microorganisms attached to the human body (90% of cells) could be the key to a lean and healthy body.

Lean and obese individuals harbour different microbes

The human gut microbiome is a highly diverse microbial ecosystem of approximately 400 different species, with most of the species belonging to the phylum Bacteroidetes or Firmicutes. Each person has an unique composition of bacteria, and it’s also clear that subsets of the population have microbiome’s that look more a like, as different diets promote the growth of certain species in the gut, and some health disorders are characterized by a specific microbial profile. By now it’s well established that obesity is associated with an “obese microbiota” that is quite different than the microbiota of a lean person (1,2).

The first studies looking into the microbiota in overweight and obesity found that obese individuals have a decreased Bacteroidetes/Firmicutes ratio, but recent findings show that this isn’t always the case. Also, since both “good” and “bad” bugs belong to both of these major groups of bacteria, the ratio between Bacteroidetes and Firmicutes doesn’t necessarily tell us much about the health of the individual. What we do know, is that the “Obese microbiota” has an increased abundance of potential proinflammatory microorganisms that are strongly associated with the systemic inflammation seen in obesity (3,4,5).

In the coming years we’ll most liekly learn more about the specific makeup of the “obese microbiota”.

Microbiota transplantation is effective in the treatment for obesity

Mice who receive microbiota from an obese person gain more weight than mice who receive a transplant from a lean individual. Transplantation of gut microbes from humans to mice also leads to metabolic changes in the rodents that are associated with obesity in humans (6).

One recent study in humans also showed that “six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota” (7).

The research into the human microbiome and it’s role in obesity is still in the early stages, and more long-term human studies looking into microbiota transplantation, prebiotics and prebiotics will appear in the coming years.

A vicious cycle

Most of the early studies on the human microbiome and it’s role in overweight and obesity focused on bacteria and energy harvesting. The assumption was that the obese microbiota was more efficient at extracting energy from food, and therefore contributed to weight gain. While this idea does hold some truth, it seems that the increased capacity for energy harvest is not that big of a deal as previously thought. Rather, it seems that gut dysbiosis, increased intestinal permeability, metabolic endotoxemia, and inflammation are the primary factors involved.

The “primary” process linking the gut microbiota to weight gain and obesity

(8,9,10,11,12,13)

  1. A western diet promotes gut dysbiosis and increased intestinal permeability
    A western diet rich in acellular carbohydrates, refined fats, and other types of highly processed food, changes the gut microbiome. Little prebiotic fiber in the diet is also an essential component associated with low production of short-chain fatty acids in the colon, dysbiosis and increased intestinal permeability. Other factors such as drug use and hygiene can also influence the development of an obese microbiota.
  2. Gut dysbiosis and increased intestinal permeability initiate metabolic endotoxemia and inflammation
    The obese microbiota has an increased abundance of proinflammatory microorganisms, and some of these microbes have a large molecule in the outer membrane called Lipopolysaccharide (LPS). LPS is able to bind to the cells lining the gut, and can also breach the intestinal barrier and therefore increase the concentration of LPS in the blood. Metabolic Endotoxemia (chronically increased plasma LPS) contributes to the low-grade inflammation that characterizes obesity and metabolic syndrome.
  3. Low-grade inflammation initiates insulin resistance, leptin resistance and weight gain
    Insulin and leptin are two of the primary hormones involved in overweight and obesity. Insulin is central to regulating carbohydrate and fat metabolism in the body, and leptin is produced by the body’s fat stores and helps the brain control the size of these stores by varying appetite and food intake.
  4. Weight gain increases systemic inflammation
    While there is a clear correlation between obesity and changes in the gut microbiota, it’s always difficult to determine what comes first – Does weight gain lead to alterations in the gut bacterial communities, or are changes to the gut microbiota driving excess fat storage?
    It seems that it can happen either way… It’s a vicious cycle where a poor diet (and other factors) leads to dysbiosis, endotoxemia, inflammation and weight gain, and increased body weight results in elevated energy intake, further damage to the gut microbiota and increased adipose tissue inflammation.

Applying the knowledge

Several factors contribute to obesity, but recent findings suggest that gut dysbiosis, endotoxemia and low-grade inflammation are especially important. Eating what resembles a healthy traditional diet based on nutrient-rich whole foods will lead to increased satiety per calorie, better gut microbiota composition, and weight loss.

Including sources of probiotics and prebiotics in the diet is also necessary to ensure a healthy gut microbiota. Lactic acid bacteria found in probiotic supplements and fermented food have been shown in scientific studies to be effective in the treatment of obesity (14, 15), and prebiotics such as resistant starch and oligofructose are an essential part of a healthy diet as they promote the growth of beneficial bacteria in the digestive tract and increase production of short-chain fatty acids.

It’s important to note that just taking a probiotic supplement from the grocery store will have little, if any effect. Rather, it seems that the combination of a healthy diet and several sources of beneficial bacteria and fermentable substrates is the best approach for treating the obese microbiota.

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