Empowering Fertility - Combating Obesity: Genetically Engineering the Microbiome 
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Combating Obesity: Genetically Engineering the Microbiome 

By Paul Bergh, MD

Obesity rates have reached unprecedented levels over the past 25 years and are now at an all-time high.  In addition to impairing fertility, obesity increases the risk for serious medical problems such as diabetes and cardiovascular disease.   Maternal obesity not only increases the risk for a complication of pregnancy and delivery but also may impact the health of the resultant children.  The scope and persistence of this epidemic has led to an effort of finding effective long-term solutions to this growing problem.

An area of investigation has focused on the impact of the gut microbiome on obesity.  The  human microbiome is the community of trillions of bacteria that reside on and in us.   Our microbiome, which is the net result of the interaction between our genes, environment, and diet, plays a critical role in many facets of our health and disease.  There are numerous reports that show a relationship between the composition of this microbial community that resides in our intestinal tract and our metabolic health including our propensity for obesity.  Experiments in mice where the microbiota of obese mice that were transferred to thin germ-free mice induced weight gain, illustrate the direct influence of the microbiome on obesity.

Taking this one step further, some investigators have been working to endow some bacteria with desirable properties through genetic engineering. Once modified, this bacteria could then be transferred to an individual’s gut to influence health and or weight.  A group led by Sean Davies at the Vanderbilt University has recently published data demonstrating this concept in mice.  They genetically engineered a strain of E. coli that is commonly used in over the counter probiotics.  The bacteria were modified to produce a hormone called N-acyl-phosphatidylethanolamines (NAPEs).  The small intestine normally secretes NAPEs into the bloodstream in response to feeding, after which, they travel to the hypothalamus in the brain where they act to induce satiety and suppress feeding.  Two groups of mice were fed a high-fat diet over the course of 8 weeks.  During this time, one group of mice were given water containing the genetically engineered bacteria.  The mice that received the bacteria had dramatically lower food intake, insulin resistance, and adiposity compared to the controls.  The positive effects of the this modified microbial ingestion persisted for four weeks after it was discontinued from their diet.

Other groups are looking at the microbiome as a delivery system for drugs that would otherwise be destroyed in the stomach.  While promising, this innovative strategy faces serious hurdles.  Our understanding of the microbiome is incomplete and meddling with such a complex microbial ecosystem may have unanticipated adverse effects.  Assuming safety issues are adequately addressed, another big hurdle will be to establish self-sustaining populations of these beneficial organisms.

The new genetic technologies are reaching  into every facet of our lives.  While Davies’ group has highlighted the importance of our microbiome and brought to light some exciting possibilities, one has to hope that this new era is ushered in responsibly.  The possibilities for improving health and well-being are great as are the dangerous of unintended consequence.

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Empowering Fertility: An educational blog for patients & healthcare professionals that empowers individuals to take charge of their fertility. Visit us at http://empoweringfertility.com.

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