Indole Derivatives of Tryptophan & Liver Health

Over the past few years, gut health has become synonymous with overall health.  We now know that gut health is strongly associated with the body’s homeostasis, or balance/equilibrium (4).

 

An imbalance in gut bacteria can lead to dysbiosis (imbalance) which can pave the way towards many diseases, including obesity, IBD, diabetes mellitus, and cancer (11), among others. Many different factors can affect the health of the gut including diet, environmental toxins, stress, and antibiotic usage. But evidence has shown that the byproducts of the microbes in the gut are crucial in disease prevention. One example being the indole derivatives of tryptophan which has been shown to promote liver health and the extraction of excess estrogen.

What is an indole?

Indole is a natural compound produced by the bacteria in the gut from tryptophan (10). Tryptophan is an amino acid. Cruciferous vegetables also contain indole.

gut-liver axis

When gut dysbiosis occurs, microbial products along with bacteria can disrupt physiology and make one more susceptible to disease in the gut or even to other organs. The products of the bacteria can act on immune system cells and as a result increase inflammation and possibly decrease apoptosis, which is the destruction of old or unhealthy cells. This can happen in the liver, and since the liver delivers bile to the small intestine, this can lead to a disruption of the gut-liver axis (2). At the same time, bacterial metabolites can break through a dysbiotic gut and enter the liver through the portal vein leading to more inflammation (3).

indole-3-acetic acid

When the microbes of the gut are fed beneficial fiber, their waste products can be incredibly healing. For instance, when microbes are fed tryptophan, the indole derivatives they produce provide beneficial effects in alcoholic and nonalcoholic fatty liver disease. The indole derivative indole-3-acetic acid, has been shown to protect the liver against any disease that is attempting to develop (4). Indole-3-acetic acid has also been shown through studies to help prevent increases in fasting blood glucose, improve insulin resistance and improve plasma cholesterol (5).

indole-3-propionic acid

Another metabolic derivative of tryptophan in the gut is indole-3-propionic acid. When indole-3-propionic acid, or IPA, is produced in the gut, it “induces the expression of tight junction proteins” (9) which improves leaky gut, preventing inflammation and toxins from moving into the blood supply. The IPA inhibits signaling which reduces the number of inflammatory cytokines leading to protection from liver injury. This is all mostly due to IPA inhibiting the production of endotoxins in the gut which would then enter the blood supply through a leaky gut and into the liver (9).

women's health

Tryptophan indole derivatives also play a strong part in women’s health. Another indole produced by the microbiota when breaking down tryptophan is indole-3-carbinol or I3C (1). I3C assists in the growth arrest and improved apoptosis to assist the liver in removing excess estrogen from the body (1). The improvement in apoptosis leads to the self-destruction of stressed cancer cells. In a study completed with 7 men and 10 women, they ingested I3C over a 2 month period. This led to a significant increase in C-2 estrogens being excreted through the urine while the levels of estradiol, estrone, estriol, and 16alpha-hydroxyestrone decreased (6). Estrogen has been shown in certain conditions to increase the growth of tumors, so by encouraging the body to remove excess estrogen, it can decrease the development of said cancers under certain circumstances (1). The body likes homeostasis!

in conclusion

To bring this full circle, indole derivatives of tryptophan essentially improve liver function. Indole-3-propionic acid helps heal up the gut by improving the function of tight junctions which form the epithelial lining of the gut. When the junctions are tighter, molecules are less likely to leak through the gut and into the blood supply. When molecules are able to move through the gut lining, endotoxins can reach the liver and wreak havoc. Since the liver delivers bile to the small intestine, the toxins can move to the digestive tract and cause other problems. When tryptophan is consumed, the byproducts contain many indoles that help support the liver and protect it against developing disease. Since most estrogen is metabolized in the liver (8), I3C assists the liver in removing estrogen hormones to prevent build-up. By simply consuming more foods with tryptophan, one can reap the benefits of liver health. In order to consume tryptophan through food sources, the National Library of Medicine recommends consuming oats, bananas, dried prunes, milk, tuna fish, cheese, bread, chicken, turkey, peanuts, and chocolate (7).

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this post was co-written by nutrition student and enthusiast Ashley Lyons

references:


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  1. Richard DM, Dawes MA, Mathias CW, Acheson A, Hill-Kapturczak N, Dougherty DM. L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications. Int J Tryptophan Res. 2009 Mar 23;2:45-60. doi: 10.4137/ijtr.s2129. PMID: 20651948; PMCID: PMC2908021.


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  1. Zhao ZH, Xin FZ, Xue Y, Hu Z, Han Y, Ma F, Zhou D, Liu XL, Cui A, Liu Z, Liu Y, Gao J, Pan Q, Li Y, Fan JG. Indole-3-propionic acid inhibits gut dysbiosis and endotoxin leakage to attenuate steatohepatitis in rats. Exp Mol Med. 2019 Sep 10;51(9):1-14. doi: 10.1038/s12276-019-0304-5. PMID: 31506421; PMCID: PMC6802644.

  2. Jaglin, Mathilde, et al. “Indole, a signaling molecule produced by the gut microbiota, negatively impacts emotional behaviors in rats.” Frontiers in neuroscience 12 (2018): 216.

  3. Belizário, José E., and Joel Faintuch. “Microbiome and gut dysbiosis.” Metabolic interaction in infection. Springer, Cham, 2018. 459-476.

  4. Texas A&M AgriLife Communications. “Natural compound in vegetables helps fight fatty liver disease: New research shows how indole can reduce inflammation, fatty deposits.” ScienceDaily. ScienceDaily, 7 February 2020. <www.sciencedaily.com/releases/2020/02/200207123746.htm>.

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