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Psychobiotics, the Pharmacology of Probiotics, and Our Body’s Naturally Innate Pharmacy

Psychobiotics, the Pharmacology of Probiotics, and Our Body’s Naturally Innate Pharmacy

About the only independent variable appearing to cause permanent change in the gut is dietary change, but did you know that your microbiome and microflora are drug manufacturers?

It’s a little known fact that one of our body’s innate pharmacies resides in our gut.

Where, exactly, in our gut, you ask?

Well, in neurochemicals isolated in various microbial species whose diversity depends on our microbiome’s health. This speaks to another emerging area of interest: probiotics as pharmacy.

This article will briefly discuss five neurochemical isolated from various genera of normal gut bacteria:

1. GABA: Lactobacillus and Bifidobacterium. GABA is the main inhibitory neurotransmitter in the central nervous system, helping to induce a parasympathetic response, and significantly impacting and regulating various processes both physiologically and psychologically. Several animal studies indicate that various species of Lactobacillus and Bifidobacterium are capable of producing GABA in the gut. (1, 2, 3, 4)

2. Norepinephrine: Escherichia, Bacillus, and Saccharomyces. Norepinephrine is a naturally occurring neurotransmitter active during a sympathetic response which is upregulated during fight or flight and acts as a stress hormone. Several animal studies have shown that various species of Escherichia, Bacillus, and Saccharomyces play a role in upregulatting and producing norepinephrine. (5, 6, 7, 8)

3. Serotonin: Candida, Streptococcus, Escherichia, and Enterococcus. Serotonin is a key hormone, an estimated 90% of which is thought to be produced in the gut, that is key in mood stabilization and happiness, as well as impacting learning, attention, and memory processes. Several animal studies have indicate that various species of Candida, Streptococcus, Escherichia and Enterococcus play a role in serotonin production. (9, 10, 11, 12)

4. Dopamine: Bacillus and Serratia. Dopamine is a key neurotransmitter in our ability to experience pleasure, as well as cognitive control in our prefrontal cortext. Several animal studies have shown that certain species of Bacillus and Serratia play a key role in the production of dopamine. (13, 14)

5. Acetylcholine: Lactobacillus. Acetylcholine is the main neurotransmitter of the parasympathetic nervous system and its receptors are present all throughout our smooth muscle, blood vessels, and even heart muscle, as it helps to downregulate the function of certain organs during rest and digest. Several animal studies show that various species of Bacillus and Serratia are capable of producing acetylecholine in the gut. (15, 16)

Resources:

  1. Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5. doi: 10.1073/pnas.1102999108. Epub 2011 Aug 29. PMID: 21876150; PMCID: PMC3179073
  2. Patterson E, Ryan PM, Wiley N, Carafa I, Sherwin E, Moloney G, Franciosi E, Mandal R, Wishart DS, Tuohy K, Ross RP, Cryan JF, Dinan TG, Stanton C. Gamma-aminobutyric acid-producing lactobacilli positively affect metabolism and depressive-like behaviour in a mouse model of metabolic syndrome. Sci Rep. 2019 Nov 8;9(1):16323. doi: 10.1038/s41598-019-51781-x. PMID: 31704943; PMCID: PMC6841999
  3. Duranti, S., Ruiz, L., Lugli, G.A. et al. Bifidobacterium adolescentis as a key member of the human gut microbiota in the production of GABASci Rep 10, 14112 (2020). https://doi.org/10.1038/s41598-020-70986-z
  4. Yunes RA, Poluektova EU, Vasileva EV, Odorskaya MV, Marsova MV, Kovalev GI, Danilenko VN. A Multi-strain Potential Probiotic Formulation of GABA-Producing Lactobacillus plantarum 90sk and Bifidobacterium adolescentis 150 with Antidepressant Effects. Probiotics Antimicrob Proteins. 2020 Sep;12(3):973-979. doi: 10.1007/s12602-019-09601-1. PMID: 31677091
  5. Lopes, J.G., Sourjik, V. Chemotaxis of Escherichia coli to major hormones and polyamines present in human gutISME J 12, 2736–2747 (2018). https://doi.org/10.1038/s41396-018-0227-5
  6. Strandwitz P. Neurotransmitter modulation by the gut microbiotaBrain Res. 2018;1693(Pt B):128-133. doi:10.1016/j.brainres.2018.03.015
  7. Galland L. The gut microbiome and the brainJ Med Food. 2014;17(12):1261-1272. doi:10.1089/jmf.2014.7000
  8. Malikina KD, Shishov VA, Chuvelev DI, Kudrin VS, Oleskin AV. [Regulatory role of monoamine neurotransmitters in Saccharomyces cerevisiae cells]. Prikl Biokhim Mikrobiol. 2010 Nov-Dec;46(6):672-7. Russian. PMID: 21261078
  9. Mayr A, Hinterberger G, Dierich MP, Lass-Flörl C. Interaction of serotonin with Candida albicans selectively attenuates fungal virulence in vitro. Int J Antimicrob Agents. 2005;26(4):335-337. doi:10.1016/j.ijantimicag.2005.07.006
  10. Yano JM, Yu K, Donaldson GP, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis [published correction appears in Cell. 2015 Sep 24;163:258]. Cell. 2015;161(2):264-276. doi:10.1016/j.cell.2015.02.047
  11. Banskota S, Regmi SC, Gautam J, Gurung P, Lee YJ, Ku SK, Lee JH, Lee J, Chang HW, Park SJ, Kim JA. Serotonin disturbs colon epithelial tolerance of commensal E. coli by increasing NOX2-derived superoxide. Free Radic Biol Med. 2017 May;106:196-207. doi: 10.1016/j.freeradbiomed.2017.02.034. Epub 2017 Feb 17. PMID: 28216386
  12. Evrensel A, Ceylan ME. The Gut-Brain Axis: The Missing Link in Depression. Clin Psychopharmacol Neurosci. 2015;13(3):239-244. doi:10.9758/cpn.2015.13.3.239
  13. Liu J, Xu F, Nie Z, Shao L. Gut Microbiota Approach-A New Strategy to Treat Parkinson’s DiseaseFront Cell Infect Microbiol. 2020;10:570658. Published 2020 Oct 22. doi:10.3389/fcimb.2020.570658
  14. Zhu F, Li C, Chu F, Tian X, Zhu J. Target Dysbiosis of Gut Microbes as a Future Therapeutic Manipulation in Alzheimer’s DiseaseFront Aging Neurosci. 2020;12:544235. Published 2020 Oct 6. doi:10.3389/fnagi.2020.544235
  15. STEPHENSON M, ROWATT E. The production of acetylcholine by a strain of Lactobacillus plantarum. J Gen Microbiol. 1947 Sep;1(3):279-98. doi: 10.1099/00221287-1-3-279. PMID: 20270627
  16. Yong SJ, Tong T, Chew J, Lim WL. Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential. Front Neurosci. 2020;13:1361. Published 2020 Jan 14. doi:10.3389/fnins.2019.01361
Three Reasons to Read My Book, “The Serpent & The Butterfly: The Seven Laws of Healing”

Three Reasons to Read My Book, “The Serpent & The Butterfly: The Seven Laws of Healing”

In my book, “The Serpent and The Butterfly: The Seven Laws of Healing,” I present a paradigm of health with a practical, evidence-based approach to naturopathic medicine.

Globally, hundreds of millions—over 157 million in the United States alone—struggle with a chronic disease such as type 2 diabetes, hypertension, and heart disease.

But through the seven laws of healing, my book offers a definitive starting point for anyone looking to understand how to prevent and resolve chronic disease.

You, too, can embrace a new paradigm of health with this practical, evidence-based approach to alternative medicine.

Here are three reasons to read my book, “The Serpent and The Butterfly: The Seven Laws of Healing“:

1. Taking a Balanced Approach to Alternative Medicine

Alternative medicine is more divided than ever before between the bright, shiny objects of the latest anti-aging tech trends and reverence for the traditional roots of ancient medical wisdom.

While trend is not destiny, tradition can also fall out of vogue and become scientifically outdated.

Both sides argue for evidence-based medicine but the question, “Whose evidence?”

Some health and wellness fads fall on a spectrum from one extreme to another, yet one truth remains constant: people are seeking vitality.

I discuss what it means to take a practical, balanced approach that integrates science and technology with traditional wisdom.

2.  How to Use the Seven Laws of Healing to Optimize your Health

Our body is our messenger, even if we don’t always like what it has to say.

In order to find true health, it’s essential to support this messenger and become fluent and conversant in its language.

We must learn how to rely on and trust the laws of healing operating within the human body, which have been not only been steadfast through time, but now have a strong evidential basis in the sciences.

I articulate the seven laws of healing and what it means to trust these laws operating within the human body along with practical means in which to apply them to optimize health and prevent chronic disease.

3. How to Live a Disease-Free Life

The Law of Disease states that disease is an imbalance caused by three things: toxicity, deficiency, and lack of energy.

A life free of chronic disease starts with the knowledge of how disease is engendered in the human organism.

Turning the concept of The Law of Disease inside-out, we have what I call The Triangle of Optimal Health, which says that optimal health is maintained by three things: a non-toxic lifestyle, adequate nutrition, and a robust vitality.

I discuss how to use this knowledge to lead a non-toxic lifestyle, maintain an adequate nutrient status, have plenty of energy, live a life free of chronic disease.

Calcium D-Glucarate, Your Microbiome, and You: A Closer Look at Hormone Regulation

Calcium D-Glucarate, Your Microbiome, and You: A Closer Look at Hormone Regulation

Calcium D-glucarate is a popular supplement with some buzz these days, used for cancer prevention, liver detoxification, and hormone regulation, but few know why exactly it’s recommended. This article will discuss why it’s used and discuss whether it’s a band-aid or a root cause approach to chronic disease.

First, let’s take a closer look at the compound itself.

Calcium D-glucarate is a calcium salt of D-glucaric acid, a non-toxic compound found in many fruits and vegetables, especially grapefruits, apples, oranges and even cruciferous vegetables, such as broccolini and Collard greens, but in trace amounts. (1)

Calcium D-Glurate and Liver Detoxification

The liver works 24/7 to help carry waste products out of your body.  

The liver has three phases of detoxification, and the middle or second phase, or Phase II, uses a process called glucuronidation, which involves processing end-metabolite hormones such as estrogen so that as end-metabolites they can safely move out of the body. (2, 3)

All steroid hormones, for example, are detoxified in the liver via glucuronidation.

Oral supplementation of Calcium D-glucarate has been shown to inhibit beta-glucuronidase, an enzyme produced by colonic microbiota heavily involved in liver detoxification. (4) This inhibitory enzyme can be produced in excessive amounts when our microbiome is compromised by a pathogenic bacterial foothold.

Beta-Glucuronidase Run Amuck

When our gut microbiota are thrown off, a state otherwise called dysbiosis, a host of byproducts are generated which can lead to dysbiosis-associated changes. (5) Some common agents which can wreak havoc on our microbiome include antibiotics, such as clindamycin, and NSAIDS, such as ibuprofen. (6, 7) And one of these dysbiosis-associated changes include the overproduction of the enzyme beta-glucuronidase. (8)

But the danger here is that if there is excessive beta-glucuronidase in the body due to pathogenic bacteria having taken ahold in the gut, then these end-metabolites of estrogen can be cleaved at the junction of (soon-to-be-excreted) toxin and glucuronic acid, and the toxin can then stay in the body and lead to the formation of carcinogens in the bowel, increasing the risk of cancer.

This whole process can lead to the promotion of enterohepatic recirculation wherein a toxic soup of toxins, hormones and even drugs circulates freely throughout the body. (9

A deeper discussion of enterohepatic recirculation can be saved for a future article, but it has been shown to lead, for example, to higher estrogen levels, which in turn increases the risk for breast cancer. 

In other words, elevated beta-glucuronidase activity is associated with hormone-dependent cancers. 

Calcium D-Glucarate to the Rescue

 

Supposedly, enter the supplement, calcium D-glucarate, to the rescue. Studies indicate that calcium D-Glucarate will actually prevent the excess beta-glucuronidase from cleaving the end-products of estrogen, allowing them to remain glucuronidated and to be excreted properly. 

Beta-glucuronidase actively conjugates estrogens into their active forms, a process which is impaired by dysbiosis and results in less circulating estrogen, which may contribute to conditions such as obesity, metabolic syndrome, PCOS, 

cardiovascular disease, and cancer. (10)

Calcium D-glucarate is thought to confer protective properties against breast cancer via estrogen clearance. 

In mice models, D-glucarates themselves appear to suppress cell proliferation and inflammation, and can also induce cell apoptosis, that is, they can potentially support proper cell death so as to keep malignancy in check. (11)

Other compounds thought to inhibit breast cancer include diindolylmethane (DIM) and isothiocyanates (sulphoraphane) found in cruciferous vegetables. (12) Hence, make sure to eat adequate amounts of these sulfur-rich foods.

In other words, it is thought that oral supplementation of calcium D-glucarate is a way of favoring the body’s natural defense mechanism by upregulating the clearance of carcinogens.

Is Excessive Beta-Glucuronidase A Calcium D-Glucarate Deficiency? 

Is the above a leading question? Somewhat. Is it a rhetorical question: Well, kind of. But the short answer is no. 

And taking calcium D-glucarate, though it may be highly indicated, especially as part of a naturopathic or functional treatment plan, is more a band-aid treatment than a root cause approach. 

In other words, the right question to be asking is, “What exactly is mediating or causing the excessive beta-glucuronidase producing dysbiosis?

In other words, the root cause isn’t even the dysbiosis. The dysbiosis is a symptom of an imbalance that likely has a multifactorial etiology that requires the assistance of a naturopathic physician or other integrative medicine practitioner.

Basically, it can be said that the imbalance is occurring in the gut and that by correcting whatever is causing the dysbiosis, that will lead to an improvement in symptomatology and potentially a resolution.

Hence, taking calcium D-glucarate is a potential first step, that should be part of a root cause oriented approach, to mitigate the effects of high estrogen but it is only a band-aid.

However, it’s best to start with restoring your gut microbiome by way of eliminating the instigators and mediators of dysbiosis, such as multiple rounds of antibiotics or a daily non-steroidal anti-inflammmatory (NSAID) such as ibuprofen, regularly eating your food intolerances, eating a Standard American Diet (S.A.D.), being in constant fight-or-flight, or any other number potential culprits known to compromise gut function.

In other words, because the microbiome is one of the main regulators of estrogen circulation, by taking care of our microbiome, our hormones are more likely to remain in balance.

However, remember to consult your naturopathic doctor, or your integrative medicine practitioner, before considering introducing calcium D-glucarate into your supplement regimen.

Resources

  1. Hanausek M, Walaszek Z, Slaga TJ. Detoxifying cancer causing agents to prevent cancer. Integr Cancer Ther. 2003 Jun;2(2):139-44. doi: 10.1177/1534735403002002005. PMID: 15035900.
  2. Dwivedi C, Heck WJ, Downie AA, Larroya S, Webb TE. Effect of calcium glucarate on beta-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol. 1990 Apr;43(2):83-92. doi: 10.1016/0885-4505(90)90012-p. PMID: 2346674.
  3. Calcium-D-glucarate. Altern Med Rev. 2002 Aug;7(4):336-9. PMID: 12197785.
  4. Gillis CC, Hughes ER, Spiga L, Winter MG, Zhu W, Furtado de Carvalho T, Chanin RB, Behrendt CL, Hooper LV, Santos RL, Winter SE. Dysbiosis-Associated Change in Host Metabolism Generates Lactate to Support Salmonella Growth. Cell Host Microbe. 2018 Jan 10;23(1):54-64.e6. doi: 10.1016/j.chom.2017.11.006. Epub 2017 Dec 21. Erratum in: Cell Host Microbe. 2018 Apr 11;23 (4):570. PMID: 29276172; PMCID: PMC5764812.
  5. Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med. 2016 Apr 13;8(1):39. doi: 10.1186/s13073-016-0294-z. PMID: 27074706; PMCID: PMC4831151.
  6. Rogers MAM, Aronoff DM. The influence of non-steroidal anti-inflammatory drugs on the gut microbiome. Clin Microbiol Infect. 2016 Feb;22(2):178.e1-178.e9. doi: 10.1016/j.cmi.2015.10.003. Epub 2015 Oct 16. PMID: 26482265; PMCID: PMC4754147.
  7. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017 Sep;103:45-53. doi: 10.1016/j.maturitas.2017.06.025. Epub 2017 Jun 23. PMID: 28778332.
  8. Court MH. Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system. Drug Metab Rev. 2010 Feb;42(1):209-24. doi: 10.3109/03602530903209288. PMID: 19821798; PMCID: PMC6174030.
  9. Roberts MS, Magnusson BM, Burczynski FJ, Weiss M. Enterohepatic circulation: physiological, pharmacokinetic and clinical implications. Clin Pharmacokinet. 2002;41(10):751-90. doi: 10.2165/00003088-200241100-00005. PMID: 12162761.
  10. Zółtaszek R, Hanausek M, Kiliańska ZM, Walaszek Z. Biologiczna rola kwasu D-glukarowego i jego pochodnych; potencjalne zastosowanie w medycynie [The biological role of D-glucaric acid and its derivatives: potential use in medicine]. Postepy Hig Med Dosw (Online). 2008 Sep 5;62:451-62. Polish. PMID: 18772850.
  11. Zoltaszek R, Kowalczyk P, Kowalczyk MC, et al. Dietary D-glucarate effects on the biomarkers of inflammation during early post-initiation stages of benzo[a]pyrene-induced lung tumorigenesis in A/J mice. Oncol Lett. 2011;2(1):145-154. doi:10.3892/ol.2010.221
  12. Thomson CA, Ho E, Strom MB. Chemopreventive properties of 3,3′-diindolylmethane in breast cancer: evidence from experimental and human studies. Nutr Rev. 2016;74(7):432-443. doi:10.1093/nutrit/nuw010
Digestive Bitters, Gentian and Skullcap in the Evidence-Based Treatment of Indigestion and Heartburn

Digestive Bitters, Gentian and Skullcap in the Evidence-Based Treatment of Indigestion and Heartburn

Digestive bitter formulas or tonics, comprised of plants such as gentian, ginger, wormwood, and dandelion, have been traditionally used to support digestive function for millennia. (1

Deficient in most modern diets, which lean heavily toward overly sweet or salty foods, digestive bitter herbs and plants were regularly consumed in ancestral diets. Digestive bitters are most effective when taken 10-15 minutes before a meal or with a meal.

For over a century now, two herbs in particular, gentian and skullcap, have been routinely combined and used as an herbal digestive bitter formulation to treat indigestion and heartburn. (2)

The doctor who pioneered this formulation is the late, great naturopathic physician, Dr. O.G. Carroll, said to be the most famous doctor west of the Mississippi in his time, operated a large clinical practice for decades out of Spokane, Washington. Dr. Carroll called his herbal formulation fifty-fifty caps because they were said to be approximately half gentian and half skullcap. (3

More can be learned about Dr. Carroll’s legacy, such as the Carroll Food Intolerance Method, at The Carroll Institute of Healing

It is a well-known fact that gastroesophageal reflux disease (GERD) is strongly associated with a condition called hypochlorhydria, wherein the pH of the stomach, which normally is around 1.5 to 3.5, is too high and so the stomach acid, responsible for activating a cascade of enzymatic and hormonal activity in the gut, is abnormally low. (4

It can be argued that modern diets tend to prolong acid suppression and lead to hypochlorhydria, impairing vitamin B12, calcium, and iron absorption, as well as leading to increased infectious risks over the long term. Also, it has been hypothesized that the intraluminal environment is altered and small intestinal bacterial overgrowth (SIBO) is promoted. As a result of SIBO, excessive fermentation occurs and leads to symptoms such as bloating, abdominal discomfort, and diarrhea. (5)

Evidence abounds that the lower esophageal sphincter will loosen and open if the acidic environment of the GI tract is not sufficient, hence, the acidic contents of the gut will reflux up into the esophagus and cause the symptoms of heartburn. (6)

The Science of Digestive Bitters

Scientists are split as to the mechanism of digestive bitters: a cephalic elicited vagal response involving the enteric nervous system versus a purely local response in the gastrointestinal tract. The truth is that it’s both. (7)

Our human genome contains 29 bitter taste receptors (T2Rs), which are responsible for all bitter ligands and stimulated when ingesting bitter foods, transferring information from our vagus nerve to our digestive organs and promoting an optimal pH in the gut. (8) In mouse models, bitter compounds have been shown to activate the T2Rs and stimulate the secretion of the hunger hormone ghrelin, which makes us feel satiated. (9)

Gentian

The herb, gentian (Gentiana lutea), also known as bitter root, is known to help keep the pH in the gut optimal as well as upregulate gut function and the ability to break down foodstuff entering the gut. (10)

As a result, enzymatic activity fires on all cylinders in the gut and adequate secretion delivers appropriate catabolic activity, facilitating breakdown and absorption. The microflora stays balanced, as well, disallowing pathogenic bacteria to take hold and engender dysbiosis. Conditions such as fungal overgrowth and ulcers associated with H. pylori bacteria overgrowth would be much less likely to occur. (11, 12)

Bitter glycoside compounds, such as secoiridoid monoterpenes, are what give gentian its bitter taste, but it also contains triterpenoids, xanthones, and other constituents. (13)

Gentian has analgesic, anti-inflammatory, and antioxidant effects. The root of gentian is used more commonly than the bark in herbal remedies. Gentian has been used for digestive disorders, such as loss of appetite, bloating, diarrhea, fullness, flatulence, and acid reflux. It has also been used for alleviating fever as well as preventing muscle spasms.

Skullcap

The herb, skullcap (Scutellaria laterifllora), soothes the digestive lining of the gut and supports gut healing, operating as a nervine, thereby calming the nervous system and helping to regulate the gut-brain axis as well as the vagus nerve connecting the brain to the gut. (14)

Skullcap possesses anxiolytic, sedative, anti-inflammatory, and antispasmodic properties. Skullcap contains flavonoids, lignins, resins, and tannins. (15)

Takeaway

As a naturopathic physician, digestive bitters are my first line of treatment, as we start with getting gut function improved. One of my favorite bitter tonics is gentian and skullcap digestive capsules.

Remember to consult your naturopathic doctor, or your integrative medicine practitioner, regarding the role that digestive bitters can play in your health, as there may be contraindications to adding them to your regimen.

Resources:

  1. McMullen MK, Whitehouse JM, Towell A. Bitters: Time for a New Paradigm. Evid Based Complement Alternat Med. 2015;2015:670504. doi: 10.1155/2015/670504. Epub 2015 May 14. PMID: 26074998; PMCID: PMC4446506. https://pubmed-ncbi-nlm-nih-gov.liboff.ohsu.edu/26074998/
  2. Editor1. (2015, December 17). The Carroll Food Intolerance Evaluation and Its Applications. Retrieved January 11, 2021, from https://ndnr.com/autoimmuneallergy-medicine/the-carroll-food-intolerance-evaluation-and-its-applications/
  3. Zap Indigestion with #50 Capsules. (n.d.). Retrieved January 11, 2021, from https://www.holistichealthpc.com/blog/zap-indigestion-with-50-capsules
  4. Kellerman R, Kintanar T. Gastroesophageal Reflux Disease. Prim Care. 2017 Dec;44(4):561-573. doi: 10.1016/j.pop.2017.07.001. Epub 2017 Oct 5. PMID: 29132520.
  5. Surdea-Blaga T, Negrutiu DE, Palage M, Dumitrascu DL. Food and Gastroesophageal Reflux Disease. Curr Med Chem. 2019;26(19):3497-3511. doi: 10.2174/0929867324666170515123807. PMID: 28521699.
  6. Reebs, D., & *, N. (2018, June 19). The Myth of GERD: It’s Not the Acid, Stupid! Dr. Ben Reebs. Retrieved January 11, 2021, from https://www.drreebs.com/the-myth-of-gerd-its-not-the-acid-stupid/
  7. McMullen MK, Whitehouse JM, Towell A. Bitters: Time for a New Paradigm. Evid Based Complement Alternat Med. 2015;2015:670504. doi: 10.1155/2015/670504. Epub 2015 May 14. PMID: 26074998; PMCID: PMC4446506. https://pubmed-ncbi-nlm-nih-gov.liboff.ohsu.edu/26074998/
  8. Bloxham CJ, Foster SR, Thomas WG. A Bitter Taste in Your Heart. Front Physiol. 2020 May 8;11:431. doi: 10.3389/fphys.2020.00431. PMID: 32457649; PMCID: PMC7225360.
  9. Janssen S, Laermans J, Verhulst PJ, Thijs T, Tack J, Depoortere I. Bitter taste receptors and α-gustducin regulate the secretion of ghrelin with functional effects on food intake and gastric emptying. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2094-9. doi: 10.1073/pnas.1011508108. Epub 2011 Jan 18. PMID: 21245306; PMCID: PMC3033292.
  10. Levy, J. (2019, September 10). The Ancient Herb that Aids Digestion, Wound Healing & More. Retrieved January 11, 2021, from https://draxe.com/nutrition/gentian/
  11. Beasley DE, Koltz AM, Lambert JE, Fierer N, Dunn RR. The Evolution of Stomach Acidity and Its Relevance to the Human Microbiome. PLoS One. 2015 Jul 29;10(7):e0134116. doi: 10.1371/journal.pone.0134116. PMID: 26222383; PMCID: PMC4519257.
  12. Sarker SA, Ahmed T, Brüssow H. Hunger and microbiology: is a low gastric acid-induced bacterial overgrowth in the small intestine a contributor to malnutrition in developing countries? Microb Biotechnol. 2017 Sep;10(5):1025-1030. doi: 10.1111/1751-7915.12780. Epub 2017 Jul 17. PMID: 28714103; PMCID: PMC5609274.
  13. Mirzaee F, Hosseini A, Jouybari HB, Davoodi A, Azadbakht M. Medicinal, biological and phytochemical properties of Gentiana species. J Tradit Complement Med. 2017 Jan 28;7(4):400-408. doi: 10.1016/j.jtcme.2016.12.013. PMID: 29034186; PMCID: PMC5634738.
  14. Awad R, Arnason JT, Trudeau V, Bergeron C, Budzinski JW, Foster BC, Merali Z. Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties. Phytomedicine. 2003 Nov;10(8):640-9. doi: 10.1078/0944-7113-00374. PMID: 14692724.
  15. Shang X, He X, He X, Li M, Zhang R, Fan P, Zhang Q, Jia Z. The genus Scutellaria an ethnopharmacological and phytochemical review. J Ethnopharmacol. 2010 Mar 24;128(2):279-313. doi: 10.1016/j.jep.2010.01.006. Epub 2010 Jan 11. PMID: 20064593.
Your Gut Is Not A Black Box, But Here Are Six Difficult-To-Stomach Facts

Your Gut Is Not A Black Box, But Here Are Six Difficult-To-Stomach Facts

Over 2,500 years ago the so-called founder of modern medicine, Hippocrates, said that all disease begins in the gut. And evidence shows us that he was right.

While an ever-expanding body of research indicates just how chronically sick our guts can make us, this doesn’t mean that the gut necessarily holds all of the answers to everything that we do not understand. 

A kind of black box to which we can open Pandora’s box…

Or does it?

The Gut Microbiome as Pathogen Protector

The gastrointestinal tract (GIT), in other words, the gut, is the largest interface between the human organism and the outer environment, deeply involved in maintaining our health. 

A giant panoply of microorganisms whose composition directly impacts our epithelial barrier and gut immune system functions is hosted in the lumen (membrane) of the gut and in the upper mucus layer.

Our health status is influenced by these microorganisms. 

For example, probiotics (good bacteria which confirm health benefits to us), can increase macrophage and natural killer cell activity, modulate immunoglobulin or cytokine secretions, as well as indirectly enhance the gut epithelial barrier, alter mucus secretion, and competitively exclude pathogenic bacteria from taking hold. (1)

Correlation, So What About Causation?

Every scientist knows that correlation does not equal causation, yet somehow that can be a difficult concept to remember to stomach at all.

It’s all correlation until somebody gets hurt, right? Cause-effect relationships between pathology and the microbiome are not well established, ad infinitum. It’s a story on repeat when it comes to health and wellness.

And then, bam! We have ourselves a mechanism of action, where the real stuff happens. Where we can dig in. Where there might be a patentable drug mechanism of action lurking in the shadows, and where there may be the ability to obtain research grant funding and warranting further research to confirm the as-of-yet unconfirmed.

For the last two decades or so we’ve heard endlessly about the microbiome and the gut-brain axis. 

But your gut is not a black box. Just because it can make us extremely sick doesn’t mean that it’s necessarily responsible for all of the things that we do not understand right now.

Fact #1: 70% Of Your Immune System Is Housed In Your Gut

Depending on who you talk to, anywhere from 60 to 80 percent of our immune cells reside in our gut. 

Not only immune cells, but approximately 100 trillion gut bacteria also reside there, comprising our intestinal microflora which can take care of pathogens as well as become pathogenic. (2)

When the Pathogen Monster Can Become Pathogenic

Basically, our immune system is inside our body, and bacteria live outside our body—or are they inside our body, and our body is outside? 

These two layers have a life-long conversation, during which millions of antibodies are generated and secreted by cells lining the gut. Our body’s homeostasis and our immunostasis go hand-in-hand.

Hence, if your gut is messed up, you just might get sick a lot more often, and you also just might be liable to get a chronic disease.

For example, the intestinal microbiota serves as a protective mediator during pneumococcal pneumonia, enhancing primary alveolar macrophage function. (3) Patients with diverticular disease have depleted anti-inflammatory microbiota associated with mucosal macrophage infiltration. (4)

Multiple pathologies are associated with dysbiosis or unbalanced gut microflora, as host susceptibility to infections, autoimmune disease, chronic disease, and even cancer, becomes heightened. (5)

Dysbiosis What???

Dysbiosis, most prominent in the digestive tract, is the condition of having microbial imbalances on or within the human organism. It can also occur on any surface or mucus membrane, such as skin, sinus, nose, lung, ear, nail, eye, or vagina.

Dysbiosis, of which dysbacteriosis is a subtype, is not so much about the germ as it is about the effect that the germ (or microbe) can have on a susceptible host. In other words, dysbiosis is about a relationship between host and microbe. (6)

Studies abound showing links between Parkinson’s disease and pathogenic bacteria, as well as the myriad associations between IBS and SIBO, and between SIBO and a host of other chronic diseases. (7, 8)

Fact #2: Probiotics Can Make Some People Sick

Interestingly, most so-called dairy free probiotics contain dairy in them, yet dairy is the most common food sensitivity in the world. (9)

Labels usually read “dairy free,” but the fact is often that a dairy culture medium has merely been washed off and regulations do not require the labeling of such. 

The reason is that most modern starter cultures originate from lactic acid bacteria that originally constituted milk microflora. The lactic acid live active culture is not considered to be dairy related because after the medium has been washed off it does not contain any milk or milk protein. (10)

Hence, many vegan or dairy-free labeled commercial probiotics may contain some tiny amount of dairy derivatives and make a person who is dairy sensitive or intolerant less healthy and produce symptoms, such as gas, bloating, and congestion, consistent with their epigenetics and constitution.

Probiotics obviously represent a powerful tool in order to reestablish homeostasis and promote gut health, but only if they are 100% dairy free for those who are sensitive to dairy derivatives.

This can occur not only via the innate and adaptive immunity, but through other mechanisms: intestinal epithelium permeability regulation, mucus secretion, and competitive antimicrobial compound secretion.

For example, three probiotics that have been shown to be 100% dairy free are Ayush 100B, MegaSporeBiotic, and Therbiotic.

Fact #3: 90% Of Your Serotonin Is Made In Your Gut

90% of our serotonin is made in the gut and can cross the blood-brain barrier. (11) Serotonin is known as the happiness neurotransmitter, and it’s also required in learning and attention.

Hence, it doesn’t take a rocket scientist to deduce that if your gut is messed up, you’ll be more likely to experience anxiety and depression, as well as symptoms of attention deficit disorder.

Fact #4: Psychobiome Aside, There May Be A Microbiome in Our Brain

New research has been coming out that we may even have good (or bad?) bacteria in our brain. (12) We have been finding more and more information about the psychobiome lately, that is, the gut bacteria that may impact how we think and feel. But what about the brain microbiome, now indicated in preliminary research findings? (13, 14)

Fact #5: The Gut Makes A Lot of Critically Important Nutrients

Not only is our microflora responsible for generating Vitamin K, essential to blood coagulation and bone metabolism, but it also plays a role in the production of the eight water soluble B vitamins, namely biotin, cobalamin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamin, required for methylation and detoxification pathways. (15)

Therefore, it stands to reason that if our gut is messed up, we may quickly become deficient in key minerals and nutrients to generally get things done in our bodies, such as metabolism, methylation, and detoxification.

Fact #6: You Can Change Your Microbiome Composition In Just One Day

It’s a fact that it only takes one day to completely change our microbiome. This can be done by what you eat, or by a dose of antibiotics. (16) Hence, be mindful of what you’re putting into your gut!

What’s Gut Got to Do, Got to Do with It?

The moral of the story is that you may not need a black box warning to discover that what you put in you will likely get out, in the long run, when it comes to gut health and living a life free of chronic disease.

However, the gut is not a black box because we know that it is where much of chronic disease first begins, to paraphrase Hippocrates.

Nurture your microbiome, nurture your psychobiome, support homeostasis and immunostasis, and keep dysbacteriosis at bay. 

Study the science of nutrition’s black box warnings and know that even though the gut may appear to be a black box at best and a Pandora’s box at worst, it’s neither. By understanding more, you can begin to nurture your microbiome and your psychobiome, support homeostasis and immunostasis, and keep dysbacteriosis at bay.

Resources:

  1. La Fata G, Weber P, Mohajeri MH. Probiotics and the Gut Immune System: Indirect Regulation. Probiotics Antimicrob Proteins. 2018 Mar;10(1):11-21. doi: 10.1007/s12602-017-9322-6. PMID: 28861741; PMCID: PMC5801397.
  2. Ahluwalia B, Magnusson MK, Öhman L. Mucosal immune system of the gastrointestinal tract: maintaining balance between the good and the bad. Scand J Gastroenterol. 2017 Nov;52(11):1185-1193. doi: 10.1080/00365521.2017.1349173. Epub 2017 Jul 12. PMID: 28697651.
  3. Schuijt TJ, Lankelma JM, Scicluna BP, de Sousa e Melo F, Roelofs JJ, de Boer JD, Hoogendijk AJ, de Beer R, de Vos A, Belzer C, de Vos WM, van der Poll T, Wiersinga WJ. The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia. Gut. 2016 Apr;65(4):575-83. doi: 10.1136/gutjnl-2015-309728. Epub 2015 Oct 28. PMID: 26511795; PMCID: PMC4819612.
  4. Barbara G, Scaioli E, Barbaro MR, Biagi E, Laghi L, Cremon C, Marasco G, Colecchia A, Picone G, Salfi N, Capozzi F, Brigidi P, Festi D. Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease. Gut. 2017 Jul;66(7):1252-1261. doi: 10.1136/gutjnl-2016-312377. Epub 2016 Sep 12. PMID: 27618836.
  5. Lazar V, Ditu LM, Pircalabioru GG, Gheorghe I, Curutiu C, Holban AM, Picu A, Petcu L, Chifiriuc MC. Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer. Front Immunol. 2018 Aug 15;9:1830. doi: 10.3389/fimmu.2018.01830. PMID: 30158926; PMCID: PMC6104162.
  6. Martinez KB, Leone V, Chang EB. Western diets, gut dysbiosis, and metabolic diseases: Are they linked? Gut Microbes. 2017 Mar 4;8(2):130-142. doi: 10.1080/19490976.2016.1270811. Epub 2017 Jan 6. PMID: 28059614; PMCID: PMC5390820.
  7. Sun MF, Shen YQ. Dysbiosis of gut microbiota and microbial metabolites in Parkinson’s Disease. Ageing Res Rev. 2018 Aug;45:53-61. doi: 10.1016/j.arr.2018.04.004. Epub 2018 Apr 26. PMID: 29705121.
  8. Borghini R, Donato G, Alvaro D, Picarelli A. New insights in IBS-like disorders: Pandora’s box has been opened; a review. Gastroenterol Hepatol Bed Bench. 2017 Spring;10(2):79-89. PMID: 28702130; PMCID: PMC5495893.
  9. Sarao LK, Arora M. Probiotics, prebiotics, and microencapsulation: A review. Crit Rev Food Sci Nutr. 2017 Jan 22;57(2):344-371. doi: 10.1080/10408398.2014.887055. PMID: 25848935.
  10. Deng Y, Misselwitz B, Dai N, Fox M. Lactose Intolerance in Adults: Biological Mechanism and Dietary Management. Nutrients. 2015 Sep 18;7(9):8020-35. doi: 10.3390/nu7095380. PMID: 26393648; PMCID: PMC4586575.
  11. Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015 Apr 9;161(2):264-76. doi: 10.1016/j.cell.2015.02.047. Erratum in: Cell. 2015 Sep 24;163:258. PMID: 25860609; PMCID: PMC4393509.
  12. Matarazzo I, Toniato E, Robuffo I. Psychobiome Feeding Mind: Polyphenolics in Depression and Anxiety. Curr Top Med Chem. 2018;18(24):2108-2115. doi: 10.2174/1568026619666181210151348. PMID: 30526463.
  13. Says:, Jami Carpenter, Zhao says: Mari Luque Says: Ramesh Chaudhary says: and Name *. “Bacteria May Live Naturally inside the Human Brain,” November 27, 2018. http://sitn.hms.harvard.edu/flash/2018/bacteria-may-live-naturally-inside-human-brain/.
  14. Pennisi E. Meet the psychobiome. Science. 2020 May 8;368(6491):570-573. doi: 10.1126/science.368.6491.570. PMID: 32381701.
  15. Ramakrishna BS. Role of the gut microbiota in human nutrition and metabolism. J Gastroenterol Hepatol. 2013 Dec;28 Suppl 4:9-17. doi: 10.1111/jgh.12294. PMID: 24251697.
  16. Le Bastard Q, Al-Ghalith GA, Grégoire M, Chapelet G, Javaudin F, Dailly E, Batard E, Knights D, Montassier E. Systematic review: human gut dysbiosis induced by non-antibiotic prescription medications. Aliment Pharmacol Ther. 2018 Feb;47(3):332-345. doi: 10.1111/apt.14451. Epub 2017 Dec 5. PMID: 29205415.
Can Mouthwash Cause Diabetes?

Can Mouthwash Cause Diabetes?

A 2017 study revealed that the use of mouthwash at least twice daily may be associated with a 50% greater likelihood of developing prediabetes/diabetes (1,2). Say what!? Is it possible that something as simple as swishing Listerine twice a day could double one’s chances of becoming diabetic?

Research into the so-called “salivary nitrate-nitrite-nitric oxide pathway” (3) has led to a growing body of evidence that there may be something to the proposed mechanism of action.

The Salivary Nitrate-Nitrite-Nitric Oxide Pathway

Interestingly, approximately 25% of the nitrate (the other 75% is excreted via the kidneys) that we absorb from our food (mostly from vegetables!) is uptaken by the salivary glands, where it becomes part of the saliva. (4)

This nitrate is then reduced by oral bacteria to nitrite, before it is swallowed and eventually converted to nitric oxide (NO). What is fascinating is that this nitrate helps these oral bacteria to produce energy via respiration in an anaerobic environment. (5)

The Role of Oral Bacteria in Nitric Oxide Production

Little research has been done on the oral microbiome. (6,7) The oral cavity is highly personalized, populated by bacteria strains of Streptococcus, Haemophilus (buccal mucosa), Actinomyces (supragingival plaque), Prevotella (subgingival plaque), and many more. (8)

Using a mouthwash that is “anti-bacterial” or “antiseptic” means that you’ll be indiscriminately laying waste to the good bacteria in your oral microbiome as you attempt to target the so-called bad guys, of which there are few. (9) Ironically, chronic gingivitis, dental caries, and even bad breath result from not having enough of the good guys.

Adding insult to injury, mouthwash is drying to the mouth, which disrupts saliva production. A little known fact is that saliva helps to remineralize the teeth, for example, using nutrient deposits such as phosphorous and magnesium. (10)

Putting The Mouth Back into the Body

The father of modern nutrition, Weston A. Price DDS, observed in his masterpiece, “Nutrition and Physical Degeneration,” that disease could be predicted by the state of oral health in the individual.

He, of course, traveled to many continents and observed dozens of natives in their original habitat, some of whom had not been affected, at least dietarily, by modern industrialized agriculture, which he found wreaked havoc on their oral health (and by extension, their overall health) when subsequently exposed

While disease begins in the gut, according to the father of modern medicine, Hippocrates, the gut does attach to the oral cavity. Perhaps the mouth can be considered to be an extension of the gut?

Nitric Oxide: Another Reason to Eat Your Veggies, Yo!

As a side note, some of the veggies richest in dietary nitrate are garlic and onions, eggplant and squash, arugula, beets, celery and rhubarb.

The Role of Nitric Oxide in Vascular Function

It is well established that nitric oxide (NO) plays an important role in vascular function in the body. (11) Nitric oxide is key to the function of our blood vessels, regulating vascular tone and blood flow, and inducing smooth muscle relaxation and vasodilation.

Without properly functioning blood vessels, hypertension and atherosclerosis are more a likely develop. Reduced levels of nitric oxide are also associated with insulin resistance. In fact, across the board diabetics have reduced levels of nitric oxide in their blood. (12)

What’s in Mouthwash?

If you love mouthwash, why not go with making your own, or at least buying all-natural mouthwash? Of course, it can be tricky figuring out exactly what “all-natural” means.

Mainstream mouthwash, for the most part, is full of artificial flavorings and colorings, with inferior essential oils, industrial chemicals (such as chlorine dioxide, an antibacterial bleaching agent), chlorhexidine (antibacterial and a common allergen) and even detergents such as sodium lauryl sulfate (common in toothpaste and to which many have a sensitivity).

Home-made DIY Mouthwash Recipe

  • Use small glass container, such as mason jar
  • 1.5 TBS baking soda
  • 1 cup distilled water
  • 2 drops tea tree essential oil
  • 2 drops ginger oil
  • 2 drops clove oil
  • 2 drops peppermint, wintergreen, or spearmint essential oil

Shake each time before using, as baking soda settles at bottom of container. Let one tablespoon swish in your mouth for 1-2 minutes. Avoid swallowing, especially when gargling.

Resources

  1. Joshipura KJ, Muñoz-Torres FJ, Morou-Bermudez E, Patel RP. Over-the-counter mouthwash use and risk of pre-diabetes/diabetesNitric Oxide. 2017;71:14-20. doi:10.1016/j.niox.2017.09.004.
  2. Preshaw PM. Mouthwash use and risk of diabetesBritish Dental Journal. 2018;225(10):923-926. doi:10.1038/sj.bdj.2018.1020.
  3. Hezel M, Weitzberg E. The oral microbiome and nitric oxide homoeostasisOral Diseases. 2013;21(1):7-16. doi:10.1111/odi.12157.
  4. Lidder S, Webb AJ. Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathwayBritish Journal of Clinical Pharmacology. 2013;75(3):677-696. doi:10.1111/j.1365-2125.2012.04420.x.
  5. Govoni M, Jansson EÅ, Weitzberg E, Lundberg JO. The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwashNitric Oxide. 2008;19(4):333-337. doi:10.1016/j.niox.2008.08.003.
  6. Gao L, Xu T, Huang G, Jiang S, Gu Y, Chen F. Oral microbiomes: more and more importance in oral cavity and whole bodyProtein & Cell. 2018;9(5):488-500. doi:10.1007/s13238-018-0548-1.
  7. Bars PL, Matamoros S, Montassier E, et al. The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tractCanadian Journal of Microbiology. 2017;63(6):475-492. doi:10.1139/cjm-2016-0603.
  8. Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the Normal Bacterial Flora of the Oral CavityJournal of Clinical Microbiology. 2005;43(11):5721-5732. doi:10.1128/jcm.43.11.5721-5732.2005.
  9. Chino T, Santer DM, Giordano D, et al. Effects of oral commensal and pathogenic bacteria on human dendritic cellsOral Microbiology and Immunology. 2009;24(2):96-103. doi:10.1111/j.1399-302x.2008.00478.x.
  10. Neel EA, Aljabo A, Strange A, et al. Demineralization–remineralization dynamics in teeth and bone. International Journal of Nanomedicine. 2016;Volume 11:4743-4763. doi:10.2147/ijn.s107624.
  11. Loscalzo J, Jin. Vascular nitric oxide: formation and functionJournal of Blood Medicine. 2010:147. doi:10.2147/jbm.s7000.
  12. Tessari P, Cecchet D, Cosma A, et al. Nitric Oxide Synthesis Is Reduced in Subjects With Type 2 Diabetes and NephropathyDiabetes. 2010;59(9):2152-2159. doi:10.2337/db09-1772.