Can Probiotics Help Increase Tryptophan Levels?

By Adin Smith, MS | Posted March 13, 2022

Bacteria Bifidobacterium, gram-positive anaerobic rod-shaped bacteria

Probiotics may help you maintain healthy tryptophan levels.

What are probiotics?

Probiotics consist of live microorganisms that benefit the host when administered in adequate amounts.[1]Hill C, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement. Nat Rev Gastroenterol Hepatol. 2014 These beneficial strains are made from bacteria or yeasts that are similar or identical to those found in the body.[2]US Department of Health and Human Services. Probiotics: What You Need To Know. Accessed 12/11/2021. Probiotics occur naturally in fermented foods like yogurt, kimchi, natto, and sauerkraut. People can also take probiotic supplements prepared in powder, liquid, capsules, or gummies.

Why are probiotics needed?

Many factors like international travel, air pollution, stress, and poor dietary choices can cause dysbiosis (an imbalance in gut bacteria), leading to health problems.[3]Fouladi F, et al. Air pollution exposure is associated with the gut microbiome. Environ Int. 2020 May;138:105604. [4]Madison A, et al. Stress, depression, diet, and the gut microbiota. Curr Opin Behav Sci. 2019;28:105-110. For instance, individuals with traveler’s diarrhea (a digestive illness caused by contaminated food or water) have an increased risk for developing irritable bowel syndrome (a common disorder of the lower digestive tract triggering abdominal pain, gas, bloating, and constipation or diarrhea, or alternating cycles of both).[5]Stermer E, et al. Is traveler’s diarrhea a significant risk factor for the development of IBS? A prospective study. Clin Infect Dis. 2006 Oct 1;43(7):898-901. A large group of studies shows that probiotic supplementation may reduce the risk of developing traveler’s diarrhea.[6]McFarland LV. Meta-analysis of probiotics for the prevention of traveler’s diarrhea. Travel Med Infect Dis. 2007 Mar;5(2):97-105. This research suggests that probiotic use may offer protection against the development of certain health problems.

How do probiotics work?

How probiotics modify our physiology is an area of ongoing research, but the immune-modulating properties of probiotics are the most frequently studied.[7]Shahrokhi M, et al. Probiotics. Updated 2021 Nov 25. In: StatPearls Internet. [8]Eloe-Fadrosh EA, et al. Functional dynamics of the gut microbiome in elderly people during probiotic consumption. mBio. 2015 Apr 14;6 A recent meta-analysis reported that probiotic use effectively lowered markers of inflammation within the blood circulation, indicating that probiotics may suppress overactive (harmful) immune responses.

Additionally, evidence suggests that probiotics may act similarly to the native host bacteria by converting food molecules into various immune-regulating compounds.[9]Gao J, Xu K, Liu H, et al. Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism. Front Cell Infect Microbiol. 2018;8:13. For instance, when the dietary amino acid tryptophan gets processed by our gut bacteria it produces several tryptophan metabolites that stimulate many vital defense mechanisms. One such protective mechanism of bacteria-derived tryptophan fragments is their ability to promote the secretion of antimicrobial peptides, a class of small molecules essential for eliminating unwanted microorganisms (i.e., certain types of fungi, parasites, and viruses).[10]Taleb S. Tryptophan Dietary Impacts Gut Barrier and Metabolic Diseases. Front Immunol. 2019;10:2113. Published 2019 Sep 10.

Although there are many other ways that probiotics may support the immune system, the primary focus of this article is to explore the interconnections between probiotics, immune responses, and tryptophan metabolism.

The importance of tryptophan

As one of the nine essential amino acids that must be obtained from the diet, tryptophan is involved in the regulation of numerous processes vital to gut health, mood, sleep, and immune system function.[11]Lovelace MD, et al. Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. Neuropharmacology. 2017 Jan;112(Pt B):373-388. 

This essential amino acid is necessary for protein synthesis (a key body process for making various protein-containing molecules). Tryptophan is also required to make serotonin and melatonin—two important chemical messengers. Serotonin is a well-known brain neurotransmitter involved in mood regulation, memory, cognition, and digestive function. Melatonin production is necessary for sleep and immune function, intestinal health, and antioxidant effects, among others. Additionally, tryptophan plays a structural role in helping stabilize membrane proteins within the phospholipid bilayer of cells.

Because tryptophan content is widely distributed in foods (i.e., eggs and dairy products, tuna, chicken, turkey, beef, peanuts, bananas, oats), most people get enough of this amino acid. However, specific health scenarios may increase dietary tryptophan requirements despite consuming a typical diet.

Reasons why some people may need more tryptophan.

Several health factors or medical conditions may lead to lower tryptophan levels in the body. Reductions in tryptophan are often associated with increased inflammation and production of the stress hormone cortisol—both of which are triggered by infection, stress, aging, or various disease states.[12]Sorgdrager FJH, et al. Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target. Front Immunol. 2019;10. [13]Lanser L, et al. Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer. Front Immunol. 2020;11:249. Published 2020 Feb 21. For instance, individuals with depression tend to have lower tryptophan levels, elevated markers of inflammation, and higher cortisol output.[14]Islam, M.R., et al. Evaluation of serum amino acids and non-enzymatic antioxidants in drug-naïve first-episode major depressive disorder. BMC Psychiatry 20, 333 (2020). [15]Myint AM, et al. Tryptophan metabolism and immunogenetics in major depression: a role for interferon-γ gene. Brain Behav Immun. 2013 Jul;31:128-33. Low tryptophan status is commonly observed in those with inflammatory bowel disease (IBD).[16]Nikolaus S, et al. Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases. Gastroenterology. 2017 Dec;153(6). Another example of individuals who typically have lower tryptophan levels is seen among patients hospitalized with COVID-19.[17]Lionetto L, et al. Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2. Biochim Biophys Acta Mol Basis Dis. 2021;1867(3):166042. These studies show that most cases of tryptophan depletion are caused by external factors (not due to a poor diet).

Can probiotics increase tryptophan levels?

Some research shows that probiotics may increase tryptophan levels. For instance, in a study analyzing the incidence of upper respiratory tract symptoms and the metabolism of tryptophan after an acute exercise bout, young athletes received a daily probiotic supplement or a placebo pill for 12-weeks.[18]Strasser B, et al. Probiotic Supplements Beneficially Affect Tryptophan-Kynurenine Metabolism and Reduce the Incidence of Upper Respiratory Tract Infections in Trained Athletes. 2016;8(11):752. At trial completion, post-exercise tryptophan levels remained unchanged in the probiotic group, whereas the placebo group experienced significant reductions in tryptophan after exercise. Individuals taking probiotics also experienced fewer upper respiratory symptoms than the placebo group. These results suggest that probiotics help maintain tryptophan content within the body, enhance immune function, and promote upper respiratory tract resilience.

In another study, healthy adults were assigned to receive a daily probiotic supplement or a placebo pill for eight weeks, followed by a four-week washout period to analyze probiotic safety, immune markers, and tryptophan metabolism.[19]Marcial GE, et al. Lactobacillus johnsonii N6.2 Modulates the Host Immune Responses: A Double-Blind, Randomized Trial in Healthy Adults. Front Immunol. 2017 Jun 12;8:655. At the end of the trial, the safety analysis revealed that the probiotic group reported fewer headaches and dizziness complaints, and less abdominal pain and indigestion. Subjects treated with probiotics also had higher tryptophan levels along with increased numbers of monocytes and natural killer cells—two types of immune cells necessary for launching an attack and slowing the spread of infection, along with preventing tissue damage. Additionally, the probiotic group experienced increases in the Th1 response—a type of immune response triggered by T Helper cells. Several conditions have associated the imbalance between Th1 and Th2 immune responses. For example, low Th1 activity relative to TH-2 activity frequently occurs in certain disease states (i.e., asthma and type 1 diabetes).[20]León B, et al. Modulating Th2 Cell Immunity for the Treatment of Asthma. Front Immunol. 2021 Feb 10;12:637948. [21]Vaseghi H, et al. Th1/Th2 cytokines in Type 1 diabetes: Relation to duration of disease and gender. Indian J Endocrinol Metab. 2016;20(3):312-316.

In a trial involving pediatric type 1 diabetic subjects (ages 3-18), participants were randomized to a daily placebo pill or probiotic supplement for three months to analyze the treatment effects on markers of inflammation and tryptophan metabolism.[22]Mondanelli G, et al. Effect of Probiotic Administration on Serum Tryptophan Metabolites in Pediatric Type 1 Diabetes Patients. Int J Tryptophan Res. 2020;13. Upon trial completion, the results showed that, compared to the placebo group, the probiotic treatment group had significantly higher increases in tryptophan blood levels. Probiotic-treated subjects had significant reductions in inflammatory secretions compared to the placebo group. Researchers also found that probiotic treatment helped maintain tryptophan by preventing overproduction of serotonin in the digestive tract. For instance, ulcerative colitis, Chron’s disease, and IBS are associated with excessive serotonin production within the gut. 

These results suggest that probiotics may help limit inflammation in the digestive tract, resulting in lesser amounts of tryptophan being broken down and utilized for serotonin production in the gut. Unlike the probiotics used in the previous two studies mentioned (which are not easily obtained by the general population), this study used Lactobacillus rhamnosus GG, the most common probiotic strain found in foods like yogurt and readily available in many probiotic supplements.

How do probiotics alter tryptophan metabolism?

When the body reacts to chemical irritation, mechanical stresses, or infection, the innate immune response triggers the release of inflammatory signaling peptides called cytokines. One of the cytokines produced, interferon-gamma (IFN-γ), activates an enzyme responsible for breaking down tryptophan, known as indoleamine 2,3-dioxygenase (IDO). Tryptophan depletion caused by IDO activation is a necessary pathway for promoting immune tolerance (a process that prevents tissues from getting damaged or “caught in the crossfire”). Although IDO activity is essential to health, consequences may arise when IDO and other protective processes are activated chronically. Thus, interfering with IDO activation may help limit excess tryptophan depletion. For instance, certain strains of Lactobacillus species produce hydrogen peroxide (H202), which may restrict IDO activation.[23]Valladares R, et al. Lactobacillus johnsonii inhibits indoleamine 2,3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats. FASEB J. 2013 Apr;27(4):1711-20. Typically, we think of H202 as a harmful substance (it certainly can be), but new research suggests that it plays a role as an essential signaling molecule in the digestive tract.[24]Acovic A, et al. Role of indoleamine 2,3-dioxygenase in pathology of the gastrointestinal tract. Therap Adv Gastroenterol. 2018 Dec 6;11.

Conclusion

Research suggests that specific probiotic strains increase tryptophan levels. Higher tryptophan levels in the blood circulation may also improve brain tryptophan levels, which could help promote serotonin and melatonin production within the brain. Overall, the tryptophan sparing properties of probiotics may represent a new mechanism for how these beneficial microorganisms can promote intestinal and immune health, cognition, and neurological function.

References

References
1Hill C, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement. Nat Rev Gastroenterol Hepatol. 2014
2US Department of Health and Human Services. Probiotics: What You Need To Know. Accessed 12/11/2021.
3Fouladi F, et al. Air pollution exposure is associated with the gut microbiome. Environ Int. 2020 May;138:105604.
4Madison A, et al. Stress, depression, diet, and the gut microbiota. Curr Opin Behav Sci. 2019;28:105-110.
5Stermer E, et al. Is traveler’s diarrhea a significant risk factor for the development of IBS? A prospective study. Clin Infect Dis. 2006 Oct 1;43(7):898-901.
6McFarland LV. Meta-analysis of probiotics for the prevention of traveler’s diarrhea. Travel Med Infect Dis. 2007 Mar;5(2):97-105.
7Shahrokhi M, et al. Probiotics. Updated 2021 Nov 25. In: StatPearls Internet.
8Eloe-Fadrosh EA, et al. Functional dynamics of the gut microbiome in elderly people during probiotic consumption. mBio. 2015 Apr 14;6
9Gao J, Xu K, Liu H, et al. Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism. Front Cell Infect Microbiol. 2018;8:13.
10Taleb S. Tryptophan Dietary Impacts Gut Barrier and Metabolic Diseases. Front Immunol. 2019;10:2113. Published 2019 Sep 10.
11Lovelace MD, et al. Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. Neuropharmacology. 2017 Jan;112(Pt B):373-388.
12Sorgdrager FJH, et al. Tryptophan Metabolism in Inflammaging: From Biomarker to Therapeutic Target. Front Immunol. 2019;10.
13Lanser L, et al. Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer. Front Immunol. 2020;11:249. Published 2020 Feb 21.
14Islam, M.R., et al. Evaluation of serum amino acids and non-enzymatic antioxidants in drug-naïve first-episode major depressive disorder. BMC Psychiatry 20, 333 (2020).
15Myint AM, et al. Tryptophan metabolism and immunogenetics in major depression: a role for interferon-γ gene. Brain Behav Immun. 2013 Jul;31:128-33.
16Nikolaus S, et al. Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases. Gastroenterology. 2017 Dec;153(6).
17Lionetto L, et al. Increased kynurenine-to-tryptophan ratio in the serum of patients infected with SARS-CoV2. Biochim Biophys Acta Mol Basis Dis. 2021;1867(3):166042.
18Strasser B, et al. Probiotic Supplements Beneficially Affect Tryptophan-Kynurenine Metabolism and Reduce the Incidence of Upper Respiratory Tract Infections in Trained Athletes. 2016;8(11):752.
19Marcial GE, et al. Lactobacillus johnsonii N6.2 Modulates the Host Immune Responses: A Double-Blind, Randomized Trial in Healthy Adults. Front Immunol. 2017 Jun 12;8:655.
20León B, et al. Modulating Th2 Cell Immunity for the Treatment of Asthma. Front Immunol. 2021 Feb 10;12:637948.
21Vaseghi H, et al. Th1/Th2 cytokines in Type 1 diabetes: Relation to duration of disease and gender. Indian J Endocrinol Metab. 2016;20(3):312-316.
22Mondanelli G, et al. Effect of Probiotic Administration on Serum Tryptophan Metabolites in Pediatric Type 1 Diabetes Patients. Int J Tryptophan Res. 2020;13.
23Valladares R, et al. Lactobacillus johnsonii inhibits indoleamine 2,3-dioxygenase and alters tryptophan metabolite levels in BioBreeding rats. FASEB J. 2013 Apr;27(4):1711-20.
24Acovic A, et al. Role of indoleamine 2,3-dioxygenase in pathology of the gastrointestinal tract. Therap Adv Gastroenterol. 2018 Dec 6;11.

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