The gut microbiome balancing act

Internal fitness, the correct balance of our gut microbiome, improves energy levels and mood, keeps us from getting sick, and even helps to protect us from devastating disease.

AM I IN BALANCE?

The importance of internal fitness

People are complex systems, and optimal health is the result of having a healthy gut with the correct balance of biochemistry and microbes populating our bodies. We call having this balance being internally fit.


Internal fitness impacts:

• Reproductive health
• Energy and metabolism
• DNA/oxidative damage
• Specific organ function (kidney, heart, eyes, CNS)
• Detection of chronic infectious diseases

Maintaining a balanced gut microbiome is critical for staying healthy.

Imbalances in the gut microbiome (called dysbiosis) have been associated with a wide spectrum of diseases such as:

  • Alzheimer's Disease
  • Parkinson’s Disease
  • MS (Multiple Sclerosis)
  • ALS (Lou Gehrig’s Disease)
  • Diabetes
  • Cancer
  • Immune system disorders
  • Heart disease
  • Acid reflux
  • IBS (irritable bowel syndrome)
  • IBD (inflammatory bowel disease)
  • Hypertension
  • Cognitive impairment
  • Obesity

FOOTNOTES

We have damaged our gut microbiome

Modern society is creating new healthcare challenges.

Damage has been caused by:

  • Foods we eat (processed foods, preservatives)
  • Products we use (xenoestrogens, petrochemicals)
  • Medications we take (antibiotics)
  • Stress

FOOTNOTES

The gut microbiome is the factory for the raw materials we need

A damaged gut microbiome:

produces an improper balance of metabolites, which makes the body more susceptible to disease.



Damaged Gut vs Healthy Gut

A healthy gut microbiome:

produces a better balance of metabolites which protects the body from disease.

Ixcela measures the balance of twelve important metabolites essential to internal fitness.

METABOLITE DETAILS

 

Lack of the right building blocks leads to poor internal health

We need the right levels of these metabolites to protect us against disease.

An explosion of evidence for the need to diagnose and treat gut microbiome health


The gut microbiome is increasingly recognized in the scientific community as crucial to personal health.

Articles on microbiome health are routinely featured in internationally recognized news sources:

• PBS: Biologists manufacture bacteria that may one day treat an unhealthy stomach" July 2015
• CBS News: "You may be damaging your body's ecosystem and not know it" August 2015
• New York Times: ”Can the bacteria in your gut explain your mood?" July 2015
• The Scientist: "How fats influence the microbiome" August 2015
• Science Mag: "Gut microbes linked to eye disease" August 2015

What we can do to improve our gut microbiome health

It is possible to modify the balance of gut microbes through:

• Healthy eating
• Exercise and relaxation
• Supplementation



1. Blaut, M et al. “Metabolic Diversity of the Intestinal Microbiota: Implications for Health and Disease.” J. Nutr. Mar. 2007.

2. Ali-Hassan-Sayegh, S et al. “Protective effects of anti-oxidant supplementations on contrast induced nephropathy after coronary angiography: an updated and comprehensive meta-analysis and systematic review.” Kardiol Pol (2016). PMC. Epub ahead of print. 17 Feb. 2016.

3. Murillo, AG and Fernandez, ML. “Potential of Dietary Non-Provitamin A Carotenoids in the Prevention and Treatment of Diabetic Microvascular Complications.” Adv Nutr 7.1 (2016): 14-24. PMC. Web. 17 Feb. 2016.

4. Rao, F et al. “Potential role of punicalagin against oxidative stress induced testicular damage.” Asian J Androl (2016). PMC. Epub ahead of print. 17 Feb. 2016.



1. Tulstrup, MV et al. “Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class.” PLoS One. 10.12 (2015): e1044854. PMC. Web. 16 Jan. 2016.

2. Bokulich, NA et al. “A Bitter Aftertaste: Unintended Effects of Artificial Sweeteners on the Gut Microbiome.” Cell Metab. 4 Nov. (2014).



1. Blaut, M et al. “Metabolic Diversity of the Intestinal Microbiota: Implications for Health and Disease.” J. Nutr. Mar. 2007.

2. Ali-Hassan-Sayegh, S et al. “Protective effects of anti-oxidant supplementations on contrast induced nephropathy after coronary angiography: an updated and comprehensive meta-analysis and systematic review.” Kardiol Pol (2016). PMC. Epub ahead of print. 17 Feb. 2016.

3. Murillo, AG and Fernandez, ML. “Potential of Dietary Non-Provitamin A Carotenoids in the Prevention and Treatment of Diabetic Microvascular Complications.” Adv Nutr 7.1 (2016): 14-24. PMC. Web. 17 Feb. 2016.

4. Rao, F et al. “Potential role of punicalagin against oxidative stress induced testicular damage.” Asian J Androl (2016). PMC. Epub ahead of print. 17 Feb. 2016.



The 12 Key Metabolites We Test

  • Indole-3-Propionic Acid(IPA)
  • Indole-3-Lactic Acid (ILA)
  • Indole-3-Acetic Acid (IAA)
  • Tryptophan
  • Serotonin
  • Kynurenine
  • Total Indoxyl Sulfate (IDS)
  • Tyrosine
  • Xanthine
  • 3-Methylxanthine
  • Uric Acid
  • 4-Hydroxybenzoic Acid

Indole-3-Propionic Acid (IPA)

Proper IPA levels are the cornerstone of internal fitness. IPA has been shown to play a very important role in gut health. (1) IPA is also considered one of the strongest antioxidants identified.* Oxidative stress is a process that results in tissue damage and cell death. IPA has been shown to protect cells from oxidative stress damage, which plays an important role in brain health.* (2) IPA is a critical marker for a healthy gut microbiome (3) and plays a crucial role by maintaining and strengthening the tight junctions (contact) between cells lining the gut.* (2) This is important for maintaining intestinal structural integrity, and decreasing intestinal permeability which can lead to substances exiting the intestine into the bloodstream, leading to conditions such as food allergies.

Indole-3-Lactic Acid (ILA)

As a precursor to IPA, ILA is crucial to internal fitness.(4) ILA is a tryptophan metabolite which is heavily involved in the creation of neurotransmitters and antioxidants that are important to healthy brain and gut function. It is important to maintain the proper balance of ILA, as too low levels , may prevent the formation of adequate amounts of downstream metabolites such as IPA, whereas too high level High levels of ILA may lead to gut dysfunction and discomfort because at high levels, ILA can be toxic to the beneficial bacteria in the microbiome.

Indole-3-Acetic Acid (IAA)

IAA is also a precursor to IPAand is crucial in attaining and maintainin internal fitness. IAA has been shown to possess antioxidant activity (5) and is heavily involved in the creation of neurotransmitters (such as serotonin) and antioxidants that are important for healthy brain and intestinal function. Low levels of IAA may be an indication of gut dysbiosis. High levels of IAA have been reported to inhibit the growth and survival of the beneficial Lactobacillus which may help to inhibit the growth of some harmful bacteria. (6)

Tryptophan

Tryptophan is important for emotional well-being and is one of the key building blocks for proteins that are essential for maintaining a healthy body. Tryptophan is also a precursor to many important metabolites: kynurenine, serotonin, and indole- 3-propionic acid. (7) Low tryptophan levels are linked to occasional difficulties sleeping and muscle aches and pains. High levels of tryptophan have been linked to mood swings, increased aggressiveness, and tremors.

Serotonin

Most of the body’s serotonin (~95%) is produced by cells in the intestinal wall. Serotonin is one of the most important signaling molecules within the gut. (8) It is crucial for normal functionality of the central nervous system and is essential for normal brain processes that affect mood, behavior, memory, and learning. Low levels have been linked to occasional sleep problems, muscle aches and pains, poor brain health, and poor gut health. (9) High levels of serotonin can be linked to shivering, diarrhea, restlessness, confusion, poor heart health, dilated pupils, muscle aches and pains, and headaches. (10,11)

Kynurenine

Its primary function is to dilate blood vessels during an inflammatory response.* It is also a regulator of the immune system* (12, 13) and is used in the production of niacin (vitamin B3). Niacin (B3) is utilized by the endocrine system to produce certain hormones.* and is one of the essential human nutrients in DNA repair.* Low levels of have been linked to decreased energy and gut dysbiosis.

Indoxyl Sulfate

High levels of IDS can lead to oxidative stress in numerous cell types including: vascular smooth muscle cells, endothelial cells, and bone cells. (14) Improper levels of IDS have been associated with poor kidney and heart health. (14)

Tyrosine

Tyrosine functions as a building block for several important neurotransmitters such as dopamine, epinephrine, and norepinephrine. Neurotransmitters regulate mood, behavior, and general feelings of well-being. Abnormally high or low levels of tyrosine can lead to poor brain health. (15)

Xanthine

Low levels of xanthine can lead to digestive discomfort due to the role xanthine plays in inducing digestive enzymes. Higher levels than normal have been linked to nausea, elevated heart rate, and poor heart health. (16)

3-Methylxanthine

Proper levels are important for maintaining the purine pathway which aids in the health of both our brain and digestive systems. High levels can be an indication of excessive caffeine intake and can lead to acid reflux. (17)

Uric Acid (UA)

UA is an indicator of the purine pathway which helps to protect our blood vessels from damage and aids in the health of both our brain and digestive systems.

4-Hydroxybenzoic Acid (4HBAC)

Low levels may be an indication that ingestion of natural, beneficial antioxidants is low. Too high levels can be an indicator of intestinal dysbiosis, intestinal permeability or leaky gut syndrome. (18)

(1) Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet AP, Qiu Z, Maher L, Redinbo MR, Phillips RS, Fleet JC, Kortagere S, Mukherjee P, Fasano A, Le Ven J, Nicholson JK, Dumas ME, Khanna KM, Mani S. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity. 2014 Aug 21;41(2):296-310.

(2) 
Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA. Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole- 3-propionic acid. J Biol. Chem. 1999 Jul 30;274(31):21937-42.

(3) Wiko WR, Anfora AT, Liu J, Schultz
PG, Lesley SA, Peters EC, Siuzdak G. Metabolomics analysis reveals large e ects of gut micro ora on mammalian blood metabolites. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3698-703.

(4) KEGG Pathway Database.

(5) Boltze KH, Brendler O, Jacobi H, Opitz W, Raddatz S, Seidel PR, Vollbrecht D.; Chemical structure and anti-in ammatory activity in the group of substituted indole-3-acetic acids, Arzneimittelforschung. 1980;30(8A):1314-25.

(6) D. C. Honey eld and J. R. Carlson. E ect
of Indoleacetic Acid and Related Indoles
on Lactobacillus sp. Strain 11201 Growth, Indoleacetic Acid Catabolism, and 3-Methylindole Formation, Appl Environ Microbiol. 1990 May; 56(5): 1373–1377 PMCID: PMC184413

(7) Visser AK, van Waarde A, Willemsen AT, Bosker FJ, Luiten PG, den Boer JA, Kema, IP, Dierckx RA. Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications. Eur J Nucl Med Mol Imaging. 2011 Mar;38(3):576-91.

(8) Joel C. Bornstein. Serotonin in the Gut: What Does It Do? Front Neurosci. 2012; 6: 16. Published online 2012 Feb 6. doi: 10.3389/ fnins.2012.00016 PMCID: PMC3272651

(9) Lee LT, Tsai HC, Chi MH, Chang WH, Chen KC, Lee IH, Chen PS, Yao WJ, Chiu NT, Yang YK. Lower availability of striatal dopamine transporter in generalized anxiety disorder: a preliminary two-ligand SPECT study. Int Clin Psychopharmacol. 2015 Feb 2. [Epub ahead of print]

(10) 15. Serotonin and GI Disorders: An Update on Clinical and Experimental Studies Marcus Manocha, PhD and Waliul I. Khan, MD, PhD, Clinical and Translational Gastroenterology (2012) 3, e13, doi:10.1038/ctg.2012.8 & 2012 the American College of Gastroenterology.

(11) 16. http://www.mayoclinic.org/diseases- conditions/serotonin-syndrome/basics/ de nition/con-20028946

(12) Wang Y, Liu H, McKenzie G, Witting PK, Stasch JP, Hahn M et al. (2010). Kynurenine is an endothelium-derived relaxing factor produced during in ammation. Nature Medicine 16 (3): 279–85.

(13) 20. Nguyen NT, Kimura A, Nakahama T, Chinen I, Masuda K, Nohara K et al. (2010). Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proceedings of the National Academy of Sciences 107 (46): 19961.

(14) Fellype C. Barreto, Daniela V. Barreto, Sophie Liabeuf, Natalie Meert, Griet Glorieux, Mohammed Temmar, Gabriel Choukroun, Raymond Vanholder, and Ziad A. Massy 
on behalf of the European Uremic Toxin
Work Group (EUTox), Serum Indoxyl Sulfate
Is Associated with Vascular Disease and Mortality in Chronic Kidney Disease Patients; Clin J Am Soc Nephrol 4: 1551–1558, 2009. doi: 10.2215/CJN.03980609

(15) Tyrosine. University of Maryland Medical Center. Retrieved 2011-03-1

(16) http://en.wikipedia.org/wiki/Xanthine

(17) http://www.webmd.com/lung/copd/ methylxanthines-for-chronic-obstructive- pulmonary-disease-copd

(18) Nicholson, J.K., Holmes, E., Kinross, J., Burcelin, R., Gibson, G., Jia, W., Pettersson, S. Host-Gut Microbiota Metabolic Interactions. Science, 2012 336: 1262-1267