Do Genes and Microbes Drive Obesity?

July 16, 2015| By Ross Campbell | Life | English

The increasingly obesogenic environment has amplified the underlying tendency for people to gain and retain excess weight. We can point to plentiful food, sedentary work and low levels of exercise as reasons we are all becoming heavier. It is easy to identify these changes and hold individuals responsible but, in this final blog in our Outlook on Obesity series, we ask what if there is an unavoidable medical cause for a person's obesity?

The genes in DNA are characterised as the "blueprint of life" because they govern our development at a cellular level where enzymes read the genetic code and manufacture proteins. The Genetic Investigation of Anthropometric Traits (GIANT) organisation, an international cooperation to study the science of human size, form and function (anthropometry), has been looking at the role genes play in determining body mass index (BMI).

A recent study from the group suggested that more than 20% of obesity is genetic. If this is true, then millions of people are obese not because of their lifestyle but because they simply have what might be termed “a large blueprint”.

Approximately 100 different BMI-associated loci were identified in the study, providing strong support for the role of the central nervous system in the development of obesity. The new genes and pathways identified were found to be implicated in insulin secretion, lipid biology and energy metabolism - all fundamental to the management of dietary intake.

These findings could lead to the conclusion obesity is a heritable condition - perhaps construed as an energy-utilization illness and hence a medical disability. If some people’s obesity really is a chronic disease governed by their genes, then this knowledge potentially opens a gateway to targeted, gene-based therapy - personalised medical treatment to tackle obesity in individuals for whom diets and exercise could never work on their own.

Knowledge of these genes begins to challenge some basic assumptions concerning diet. The recommendation to limit saturated fat to 30% of energy intake has been widely promulgated for decades. We automatically attribute saturated fat - butter, lard and oil - with elevating blood cholesterol and increasing vascular disease risk, and assume a diet low in saturated fat is healthy.

But the science backing these assumptions is now understood to have been flawed. The role that fat alone plays in heart disease may have been overstated and led to the neglect of other causal factors in our diet.

It is now commonplace knowledge that our own genes can influence our physical makeup but what is less well-known is that the genes of other organisms can directly affect us, too. The bacteria and microorganisms that inhabit the gut differ from person-to-person and offer another potential explanation for obesity.

Gene sequencing of the microbiome has revealed differences in the microbiota (the colonies of microbes) between people with differing BMIs. Understanding the role of particular bacteria offers potential for managing obesity in some individuals.

To visualize how this could work, consider Fecal Microbiota Transplantation (FMT), a medical procedure that introduces healthy donor bacteria into the gut of another person. FMT is proving a successful treatment for some gastrointestinal diseases.

A patient with intractable C. difficle infection made the news having received a fecal transplant from an apparently healthy donor. Alarmingly, her BMI climbed from 26 to 34.5 kg/m2 in the months following FMT. At the same time the donor also became obese, raising suspicion that some of the transplanted bacteria could have affected the recipient’s metabolism in a negative way.

Highlighting microorganisms as an explanation for excess weight gain is food for thought, whilst linking obesity to genes may be a giant step forward in understanding that some obesity can occur irrespective of the environmental cues that lure so many into eating beyond their calorific requirements.

Visit further blogs in the Outlook on Obesity series for more on the global challenge that obesity presents insurers.

  1. Locke, A E et al. (2015) “Genetic studies of body mass index yield new insights for obesity biology”. Nature 518, 197-206.
  2. Alang, N and Kelly, C R (2015) “Weight gain after fecal mircobiota transplantation”. Brief Report Open Forum Infect. Dis, DOI: 10.1093/ofid/ofv004.


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