Technology

The GI Microbiome

An ecosystem resides within us in our gastrointestinal (GI) tract.  It has an outer boundary defined by the cells of our intestine and a layer of mucus that protects these cells from the inner components of the ecosystem.  This ecosystem is complex: undigested and partially digested nutrients, microorganisms also called microbiota, important chemical molecules only produced by the microbiota, such as vitamin B12, and nonfood-derived chemical molecules that we ingest, such as drugs and potential allergens in foods and drinks.  The microbiome of an average adult can weigh at least 3 pounds.

A healthy GI microbiome contains a vast diversity of living organisms. A loss in diversity in the GI microbiome is a common finding in many disease states.  Each species in the biome uses nutrients for energy in their own special way, and by that process generates unique molecules that may signal messages about appetite and the state of digestion to systems of our bodies. By our dietary choices we select nutrients that can be used by some species, providing them a competitive advantage over other GI microbiota. The less nutrition we provide to the ecosystem in the lower GI the harsher it is for some of the bacteria that would ordinarily be abundant.  If we eat primarily simple carbohydrates and too few fermentable complex carbohydrates and fibers, many species may wither away.  The better we nourish the lower GI with sufficient levels of needed nutrients the greater the diversity.  The diversity of diet matters also.  The more diverse the diet, the more diverse the microbiome and the more adaptable it will be to perturbations (1).

 

Dietary Desert vs. Diversity

Unfortunately, modern diets can lead to an absence of nutrients in the lower GI both in quantity and diversity and result in important physiological consequences.  Diversity has been lost during the past 50 years because of economic pressures for greater food production to support a growing world population—there are fewer types of foods consumed and those that are consumed in abundance  simply do not reach the lower GI, leaving the environment inhospitable for many species that would have been naturally present 100 years ago. This decline in varied edible plant varieties and animal breeds is occurring at an incredible rate.

According to the Food and Agricultural Organization of the United Nations (2), 75 percent of plant genetic diversity has been lost, as farmers worldwide have left their multiple local varieties for genetically uniform, high-yielding varieties.  Agricultural practices of using antibiotics as growth promoters for poultry, swine and cattle further narrow the GI microbiome because the GI microbiome is exposed to those antibiotics (3).  Crop agricultural practices rely on the use of pesticides to protect plants from damage caused by weeds, fungi, and insects. Residual pesticide in food crops may be sufficient to alter the GI microbiome when consumed. Thus, economic pressures force agricultural practices that have limited the richness of the GI microbiome over the past century.

Many live in a world of food abundance that has had an unintended consequence.  Some of the more abundant foods are food products that do not nourish the bacteria and biota in the lower GI.  This can lead to an individual being able to gain tens of pounds of excess body weight while actually decreasing the amount of the required nourishment in the lower GI to satisfy the biota.  In turn, the biota does not produce the molecules that serve to signal to our bodies that we have eaten.  We can remain hungry after consuming simple carbohydrates.  The longer-term satisfaction—satiety—is triggered when complex carbohydrates are part of our diet.

Intentionally excluding nutrients from a diet could also eliminate crucial microbiota. Although temporarily excluding an essential nutrient will only briefly reduce diversity, such losses of microbiota cannot be reversed after prolonged elimination of nutrients (4). It follows that fad diets also reduce microbiota richness if the dietary plan eliminates one or more dietary macronutrients, such as all carbohydrates.

 

GI Microbiome Dysbiosis

The condition of the GI microbiome when it has shifted away from a healthy state is referred to as a state of dysbiosis or pathobiosis (5).  Dysbiosis of the GI microbiome is associated with disease. The strategy of MBT is to deliver multiple key nutrients to the GI microbiome to expand microbiota diversity, thus helping to reduce the dysbiosis and improving microbiome-generated signaling associated with health.

 

GI Microbiome Modulators (GIMMs pronounced gems)

GIMMs are designed by MBT to be restricted to the GI track. Our GIMMs have mechanisms of actions in the GI microbiome and thus offer a level of safety as they are not absorbed into the blood.  There is also a reduced potential for a GIMM to interact with the metabolism of drugs that are orally absorbed. We believe that GIMMs are ideal partners to be used in combination with current and future orally available anti-diabetic medications and to be used along with many fad diets.  Our innovative approach is to expand the narrow, pathobiotic microbiota signature associated with modern diets and some dietary interventions that lack key micronutrients. This approach aims to provide significant missing dietary elements required for a healthy GI microbiome in a safe, convenient form without contributing significant calories.

 

References

  1. Heiman ML, Greenway FL. A healthy gastrointestinal microbiome is dependent on dietary diversity.    Mol Metab 5(5):317-320.
  2. What is Agrobiodiversity? Food and agriculture organization of the United Nations. 2004 (http://www.fao.org/3/a-y5609e.pdf)
  3. Cho, I, et al. Antibiotics in early life alter the murine colonic microbiome and adiposity. 2012. Nature 488: 621–626.
  4. Oin J, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. 2012. Nature 490: 55-60.
  5. Gilbert JA, et al. Microbiome-wide association studies link dynamic microbial consortia to disease.  Nature 535:94-103.