GI Microbiome

A vast ecosystem resides within our gastrointestinal (GI) tract–the microbiome of an average adult can weigh 3 pounds! 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 exclusively 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.

A healthy GI microbiome contains a vast diversity of living organisms. A loss in diversity in the GI microbiome is common in many disease states.  Each species in the biome uses nutrients for energy in their own special way, generating unique molecules that signal a variety of messages to other systems in our bodies, including messages about the state of our appetite and digestion.

Our dietary choices provide nutrients to the GI tract that can be preferentially used by some species, providing them a competitive advantage over other GI microbiota. Unfortunately, modern Western diets frequently provide too little nutrition for some of the “beneficial” bacteria that would ordinarily be abundant.  When we eat primarily simple, digestible carbohydrates (such as sweets and pizza) and too few fermentable, non-digestible carbohydrates (such as fiber-rich foods and other prebiotics), many species that would typically reside in our GI tract may wither away, resulting in a loss of microbiota diversity and domination by species with less positive health effects.

The more we nourish and nurture the microbiota in the large intestine with sufficient levels of needed nutrients, the greater the diversity of the GI microbiome.  Greater dietary diversity produces more diverse microbiomes, which have been shown to be more adaptable and resilient in managing short term stresses and changes (1).

Prebiotic –  Probiotic – Postbiotic

Prebiotic means “before life.” Prebiotics are “food” for microorganisms—they provide nutrients for energy and are also used as building blocks for microbiota to manufacture unique substances important to their survival (and potentially for our health).  For example, Inulin is a prebiotic used by microbiota in our GI tract to manufacture important signaling molecules that participate in regulating how much we choose to eat and how we metabolize our food. Polyphenol antioxidants are prebiotics that can be used as building blocks for some GI microbiota to manufacture signaling molecules and for other microbiota to manufacture complex antibiotic substances that protect against potential pathogens in the gut.

A Probiotic is a live isolated specie of microbiota or a collection of multiple species.  These are often packaged as food or as capsules containing 1 billion to 10 billion per serving.  The dose of probiotics that can be delivered is very small in the context of the vast GI microbiome ecosystem and probiotics also depend on the availability of prebiotic nutrients for their survival and function.  Examples of probiotics are Lactobacillus and Bifidobacteria.

Postbiotic is a term meaning “after life”.  A postbiotic is a specific molecule manufactured by the microbiota. Some of those molecules are short chain fatty acids such as butyrate used as energy by cells of the intestine and are produced by Bifidobacteria. Molecules produced by microbiota can also serve as signals, sensed by the cells in the GI tract.  In turn, these cells are stimulated to produce hormones in the gut that are active elsewhere in the central nervous system.

Penicillin is a postbiotic used as an antibiotic drug produced by the fungus Penicillium that uses nutrients (prebiotic) in bread as building blocks.  In fact, most current antibiotic drugs were first discovered as postbiotics.  Vitamins K, B vitamins, biotin, and even the neurotransmitter serotonin are examples of molecules produced by microbiota in our gut that offer potential health benefits if there are sufficient quantities of prebiotic nutrients to nurture them.  Postbiotics can be considered the natural by-product of the GI microbiota and may emerge as therapies in the years to come.

 

The Modern Diet: Dietary Desert vs. Dietary Diversity

As noted, modern diets can provide insufficient nutrients in the large intestine in terms of both quantity and diversity with potentially important physiological consequences.  Diversity has been lost during the past 50 years as industrialized food production has become dominant and consumers have increasingly gravitated to heavily processed foods that are inexpensive and designed for tastiness and convenience. As a result, there are fewer types of foods consumed and those that are consumed in abundance simply do not provide the complex nutrients needed by the microbiota, leaving the GI environment inhospitable for many species that would have been naturally present for most of human history.

According to the UN Food and Agricultural Organization (2), 75% of plant genetic diversity has been lost, as farmers worldwide have abandoned their multiple local varieties for genetically uniform, high-yielding crops.  Agricultural practices that use antibiotics as growth promoters for poultry, pigs and cattle further narrow the GI microbiome since the residual antibiotics in the meat kill off some of the important species resident in the GI tract. (3).  Crop agricultural practices rely on the use of pesticides to protect plants from damage but residual pesticides on the fruit and vegetables may be sufficient to alter the GI microbiome when consumed.

Many of us live in a world of food abundance that has had unintended consequences.  In addition to providing excess calories, some of the more widely-consumed foods do not nourish the GI microbiota.  This can lead to individuals gaining many pounds of extra body weight while failing to obtain the nutrients needed to nourish a diversity of microbiota in the large intestine.

The depleted biota that results is not able to produce many of the signaling molecules typical of a healthy microbiota, including those that signal to our bodies that we have eaten enough.  For example, many of us notice that we can remain hungry after consuming foods containing easily digestible simple carbohydrates.  The longer-lasting satisfaction—satiety—is triggered, with the help of a diverse GI microbiota, when the undigestible carbohydrates in high fiber foods such as vegetables and whole grains that nourish these “beneficial bugs” are a regular part of our diet.

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

 

GI Microbiome Dysbiosis

The condition of the GI microbiome when it has shifted away from a healthy balanced state is referred to as dysbiosis or pathobiosis (5).  The strategy of MBT is to deliver multiple specific nutrients to the GI microbiome designed to support healthy microbiota diversity and the microbiome-generated signaling associated with health.

 

GI Microbiome Modulators

Our innovative approach is to develop supplements to expand the microbiota signature associated with modern diets and some dietary interventions that lack micronutrients for the GI biota. This approach aims to provide missing dietary elements required for a healthy GI microbiome in a safe, palatable, convenient form without contributing significant calories.  Our products include a carefully formulated blend of prebiotics created to nurture and nourish the microbiota.

MBT’s GI microbiome modulators are natural products derived from food that promote a diverse, healthy GI microbiome. They are designed to remain and function solely within the GI tract and are not absorbed into the bloodstream.  There is also a reduced potential for GI microbiome modulators to interact with the metabolism of orally administered pharmaceuticals, since these microbiome modulators are active only in the large intestine, while most drugs are absorbed earlier in the digestive process.

Our initial GI microbiome modulators have been clinically tested in individuals with prediabetes and in individuals experiencing GI disturbances when taking the drug metformin.  We believe they may be valuable as an aid to help maintain a healthy gut, control hunger and maintain mealtime blood sugar levels that are within the normal range.

Our supplements also may be helpful to those consuming modern diets who want to have a more diverse, health-promoting GI microbiome, and they may be especially helpful to the many who try fad diets.

 

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. Qin 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.