The Role of the Gut in Detoxification

Updated: Jul 20

The body has a built in detoxification system ready to address potential exposure to toxins, because, let’s face it -- the planet can have some hidden dangers! There are approximately 80,000 different pollutants and toxins in the general environment. We know that these substances are present in the air, on our food, in the soil and in our water. Simple steps to remove these toxins include things like air filters, water filters, glass containers, stainless steel cookware and buying organic foods. But, even with all these intentional lifestyle changes, we are still exposed to environmental substances that will enter the body on a daily basis. We all know that the body has a detoxification system, but how exactly does it work? How is the gut involved, and how can we make sure that we are helping our body rather than hindering it?

What body systems are involved in the detox process?

Removing toxins is so important for the body to address that there are several body systems involved in the process. The organs most commonly discussed in the detox pathways include the liver, lungs, kidneys and skin. Less commonly discussed detoxification systems include the epithelial (single cell layer that covers some organs) barrier and the microbiome.

What happens when a toxin enters the body?

Toxins can enter the body in multiple ways. They can be absorbed through the skin, inhaled and absorbed through the lining of the lungs or ingested and absorbed through the gastrointestinal (GI) tract. For this article, we are going to focus on ingested toxins. When a toxin is ingested it is confronted by both the epithelial lining of the GI tract and the forces of microbes in the GI tract. If a toxic substance manages to make it past these initial defenses it will then be sent to the liver for processing. The liver will either move it to the bile system where it will be excreted through feces or send it into circulation where it will be filtered through the kidney and excreted in urine.

What does the gut have to do with it?

Over the course of a lifetime, the gastrointestinal tract of an average human will have digested over 25 tons of food, making this the largest load of toxins and antigens entering the body. The intestinal epithelial lining (when healthy and functioning properly) acts as a physical, chemical and biological barrier to prevent absorption of harmful compounds. The cell lining in the gut has a detox system, making enzymes to help break down harmful chemicals and proteins to eliminate them directly.

The liver is most commonly associated with detox due to its specific enzyme pathways which help breakdown substances that enter the body (such as drugs, alcohol, caffeine, medications and toxins). These pathways include the CYP450 metabolizing enzymes. Research demonstrates that cells in the lining of the small intestine express these same CYP450 enzymes, making the small intestine the largest extrahepatic (outside the liver) site of Phase 1 detoxification.

Once pollutants are broken down, they need to be eliminated from cells and prepared for excretion. One method of excretion is to bind molecules to a transport protein that will carry them out of the body, this is Phase 3 detoxification. The cells lining the GI tract are responsible for making these proteins (called anti-porter proteins) which bind to and eliminate toxic molecules.

To recap, in a healthy GI tract the cells in the lining of the small intestine serve three functions. They act as a barrier preventing absorption of large molecules and toxic substances. Additionally these cells behave similarly to the liver - participating in Phase 1 detoxification through the CYP450 enzyme pathway to break down substances into smaller molecules. Finally they assist Phase 3 detoxification by creating anti-porter proteins responsible for elimination of molecules.

What is the effect of the microbiome on toxic substances?

Research uncovers more information regularly regarding the interplay between the microbiome and the host (human). At this time, we know what we ingest directly affects the microbiome and conversely the microbiome directly acts on what we ingest. The chemical interactions of both the host and the microbiome are regulated by the genetics of each.

The microbiome in the gut acts directly on the substances we ingest. These microbes are involved in metabolizing the chemical structures of compounds in multiple ways, including -- you guessed it! -- using the CYP450 enzyme pathway. They directly impact absorption, distribution and excretion. Beneficial micro-organisms are known to bind with heavy metals, preventing their absorption. Additionally, they act directly on the lining of the GI tract helping to maintain its integrity and influencing its permeability.

The CYP450 enzyme pathway in humans has about 57 recorded enzymes, but the microbiome has nearly 3000 predicted enzymes present. This is due to the significant genetic variability of a healthy diverse microbiome. More and more evidence demonstrates that microbes act on ingested substances with a variable effect depending on the health and diversity of the individual microbiome - resulting in a noticeably variable response to medications among individuals. This same variable response occurs between individuals and their ability to detoxify and remove chemicals and pollutants from the body.

Molecules that have undergone Phase 1 detoxification in the liver are released into the gut for Phase 2 detoxification - which is basically the next phase in breaking down these substances. This is where microbes come into play again, performing various chemical reactions known as methylation, sulfonylation, hydroxylation and other changes. Once these molecular reactions occur, compounds are reabsorbed back into the liver to prepare for Phase 3 (elimination).

Although the microbiome often assists with the detoxification process, microbial breakdown of harmless substances is not always beneficial. We know that dysbiosis (unhealthy levels of beneficial microbes) can affect the toxicity of certain substances. Polycyclic aromatic hydrocarbons (PAH) are carcinogens found on charcoal grilled meat and unwashed vegetables from contaminated soils. PAH would generally pass through the body unabsorbed. The microbiome converts PAH into estrogen-like substances which act as endocrine disruptors.

Studies show that microbes act on arsenic (often inert in nature), turning it into a far more toxic form of arsenic (organic) once ingested. Further studies show that the microbiome associated with a Western diet (low fiber) shows increased activity to produce this toxic organic arsenic.

To recap, a healthy microbiome helps maintain the integrity of the protective epithelial layer along the GI tract. Microbes metabolize and breakdown substances using many pathways including the same CYP450 pathways as the liver. A hea