Nov. 12, 2019; Opinion by Thomas E. Levy, MD, JD (OMNS October, 2019) While it is widely realized that the gastrointestinal tract has a very large presence of microorganisms, how large this presence is and how significant it is in supporting and modulating normal metabolic functions throughout the body are not as widely appreciated. In the scientific literature, this microbial ecosystem, referred to as the microbiome, colonizes the entire alimentary tract, extending from the mouth to the anus. While it is estimated that every human has roughly 37 trillion cells, it is also estimated that everyone has about 100 trillion microbes. 
The Gut Microbiome
This enormous microbiome is typically a diverse array of bacteria, fungi, protozoa, and viruses, and it is found in all mammals. Many physiological processes are positively impacted and even greatly dependent upon a normal microbiome, including energy homeostasis, metabolism in general, the health of the gut lining, immune functions, and even neurobehavioral development.  The gut microbiome is viewed by some as a “microbial organ” because of these physiological and pathophysiological interactions with the rest of the body.  Less diverse microbiomes, with greater amounts of pathogens rather than friendly microbes, have been associated with, and are likely causative for, nearly 40 diverse medical conditions. These include allergies, mood disorders, autism, digestive diseases, cardiovascular ailments, and several types of cancer. (Scroll down to the end of this article for a complete listing.)
Clinical Pathogen Presentations
Pathogen presences and aggregations in the body generally come in three basic forms:
- Body-wide, as exemplified when one is sick with the flu
- Focal and concentrated, best exemplified by infected teeth, gums, or tonsils, generally associated with, or capable of readily generating, identifiable accumulations (abscesses)
- Chronic pathogen colonization (CPC). This pathogen presence is less focal, with a chronic area of overgrowth but with overall lesser concentrations (compared to focal infections). These pathogen accumulations are capable of ongoing but limited growth and the regular generation of exudates, but not generally frank abscesses. The chronicity of the colonization is largely assured by the formation and persistence of “protective” biofilms, largely composed of an organized matrix of extracellular polysaccharides. [54,55] Such a biofilm permits the pathogens to have a sustained presence. Furthermore, a biofilm can increase the resistance to various antibiotics by up to 1,000-fold.  Not surprisingly, no antibiotic can kill pathogens that it cannot physically access.
The presence of focal infections and abscesses throughout the body is a well-known pathology, as is the ability of the body to be systemically infected, as with the flu or sepsis. However, CPC, commonly found on the mucosal linings in the oral cavity, the lungs, and throughout the alimentary tract, has not yet been recognized as a condition of great clinical importance, even though it is very common. To the contrary, however, CPC, with its intimate relationship to general gut health, is of enormous clinical consequence in many different medical conditions.
Treating the Abnormal Microbiome
When CPC is present throughout all or most of the gastrointestinal tract, antibiotics are almost never the definitive cure. In fact, for many individuals, their first significantly abnormal microbiomes were precipitated by courses of various antibiotics. Probiotics are very popular supplements these days, and many of them can very positively help certain individuals. However, many different probiotic formulations are available, and some of them may have no positive impact or even some negative impact on certain individuals. Generally, establishing an effective probiotic therapy depends upon a largely trial-and-error approach, depending on whether a clearly positive clinical impact occurs. No two GI tracts affected by CPC are identical in the diversity and amounts of the various pathogens. As a very general consideration, a probiotic that has high concentrations of various strains of Lactobacilli and Bifidobacteria is usually a good one to try, and it is probably best if it includes a prebiotic blend that helps the new microbes “feed” and take hold in recolonizing the gut. 
Probably the most important factor to address in normalizing a gut with established CPC is to eliminate as much as possible the “seeding” of new pathogens into the gut on a daily, “24/7” basis. This seeding occurs because of the chronic swallowing of pathogens and their associated toxins from areas of CPC in the mucosa of the sinuses, oro- and nasopharynx, oral cavity, and both upper and lower respiratory tracts. An especially important and very commonly neglected reservoir of such pathogens resides on chronically colonized and overgrown tongues.  Most individuals with CPC anywhere else in their alimentary tract have an abnormal tongue flora.
The tongue typically has a very heavy biofilm covering an array of anaerobic bacteria, viruses, fungi, and even protozoa. Furthermore, chronically impacted and rotting food particles are often found in the many fissures and microscopic papillae (tiny finger-like projections on the surface of the tongue) trapped under this biofilm. Your tongue has no way of naturally ridding itself of this noxious overgrowth. Just as your hands or any other part of your body cannot spontaneously clean themselves, neither can your tongue.
Patients with thicker tongue coatings have been shown to have significantly higher serum CRP (C-reactive protein) levels than patients with thinner tongue coatings. This suggests that the presence of CPC on a chronically-coated tongue is capable of causing body-wide increased oxidative stress, as reflected in the increased CRP levels.  The mechanical removal of the tongue biofilm, especially when tongue scraping is part of the removal protocol, is often an effective way to treat refractory halitosis. [60,61] Pathogen metabolism produces bad smells, while the metabolism of normal flora does not.  It has also been shown that the pathogens commonly seen with periodontal disease are closely related to the foul-smelling tongue coatings. 
Because of this, the overgrown tongue plays the leading role in the sequence of pathogen sources that must be addressed in order to achieve an optimally healthy gut. Each source must be individually addressed. The protocol for restoring and maintaining a healthy tongue should include the following:
- Use any commercially available tongue scraper to mechanically remove as much biofilm, pathogen, and pathogen-related debris as possible. This really only takes seconds. Many YouTube videos demonstrate this simple technique. This should be performed at a minimum of twice daily (first thing in the morning, last thing at night). Optimally, it should be done after every meal, which can always reseed new food particles into the microscopic tongue crevices. The rate of reformation of tongue coatings indicates that daily cleaning is indicated. 
- Whenever you brush your teeth, it is always best to do it after you scrape your tongue. Routinely brush your tongue as well with your toothbrush and toothpaste.
- Swish and gargle with an antiseptic mouthwash after every scraping.
- Consider oral irrigation on a regular basis, and always at least daily before retiring at night to minimize the rotting of retained food particulates.
Nebulization is a process that converts a liquid form of a medication into a fine mist that can be readily inhaled, facilitating direct contact of the nebulized agent with the mucosal linings of the sinuses, oral cavity, throat and respiratory tract.  The multiple benefits of nebulization include the following:
- Provides a direct route of drug administration, such as for asthma and bronchoconstriction
- Moistens inhaled air and promotes the mobilization and expulsion of tenacious mucus or other secretions
- Allows a direct contact of anti-pathogenic agents with areas of CPC
- Allows the use of anti-pathogenic agents in lower doses than what are needed for systemic administration, with lessened risk of medication toxicity or other side effects
- Offers a means to directly attack and break up tenacious biofilms
To date, there is still no consistently effective way to completely destroy/disrupt a persistent biofilm and kill the protected pathogens through the use of prescribed medicines. This is a primary reason why so many individuals have largely treatment-resistant chronic sinusitis, chronic cough, and chronic mucus production with various degrees of impaired ability to freely breathe, especially when trying to get a good night’s sleep.
Two substances that are especially effective in stripping away biofilms to permit the effective application of anti-pathogen measures are hydrogen peroxide and dimethyl sulfoxide (DMSO). [66-69] When dealing with chronic conditions in the sinuses and pharynx, it is probably best to first nebulize with hydrogen peroxide (1 to 5 cc of 3% peroxide with volume brought up to 10 to 12 cc with filtered water) for about 15 minutes or so, and then follow with nebulization of any of a number of other agents.
Alternatively, DMSO can be readily combined with other anti-pathogen agents, such as sodium ascorbate (vitamin C) and magnesium chloride. Anecdotally, this DMSO-vitamin C-magnesium chloride combination has proven to be very effective in clearing biofilms and their underlying pathogen colonies. This can be done with 1 to 5 cc of 99.9% DMSO brought up to 10 to 12 cc with a combination solution of vitamin C and magnesium chloride. Precise concentrations are not critical, and the combination solution can be quickly and easily made by adding about 2 teaspoons of sodium ascorbate powder and 2 teaspoons of magnesium chloride powder to about a half cup of water. Since the sodium ascorbate will oxidize over several hours as it turns yellow, it can be made separately from the magnesium chloride solution, which remains very stable and does not significantly deteriorate over time.
Remember that probiotics, nebulization, and regular tongue and oral hygiene measures all separately impact the gut microbiome in a positive manner. Nevertheless, the combination of any two or all three of these interventions can be expected to have a synergistic impact rather than just an additive impact in establishing and maintaining a normal or near-normal gut microbiome. And a normal gut microbiome should also prove to be very synergistic in optimizing the beneficial effects of any clinical treatment protocol.
I am offering my opinions based on clinical experience and the medical literature. You should consult and work with your own personal physician.
- For restoration/maintenance of normal gut microbial flora and normal gut function, take a probiotic supplement daily, follow the tongue hygiene protocol as described above, and nebulize the DMSO-vitamin C-magnesium combination as described above at least once daily.
- For an acute cold or early onset of influenza or other suspected viral syndrome, nebulize the DMSO/VC/magnesium combination for 15 to 30 minutes several times the first day. Anecdotal evidence suggests that almost complete resolution can often be seen by the next day. Continue daily as frequently as desired until there are no longer any symptoms.
- For an established cold or other infection where there is likely a significant biofilm present, the same protocol as above can be followed, or an initial nebulization with hydrogen peroxide can be done to help assure a more complete access to the pathogens with subsequent nebulizations.
- Nebulization can be done with babies as well. Just be sure to have the ability to suction out secretions promptly as the treatment will result in a temporary increased flow of mucus and mobilization of infected secretions.
- As long as a nebulization is well-tolerated a wide variety of non-prescription agents can be nebulized, alone or in various combinations. You can determine over time if something works better for you than the recommended DMSO/vitamin C/magnesium combination. A partial list of such agents includes: N-acetyl cysteine, sodium bicarbonate, nascent iodine, colloidal silver, zinc, and glutathione. However, in general, avoid nebulizing and inhaling any agent that is fat-soluble or oil-based.
To my knowledge, there is no direct research available on the protocol I am recommending, since I assembled it to deal with my own problems. I can only say that I have seen the protocol promptly eradicate acute viral infections. It also promptly relieved non-specific dry coughing spells. Most significantly for me, it has largely resolved (gradually over a four- to six-week treatment period) a chronic sinusitis and nagging cough of roughly 60 years duration. For me it has been nothing short of a minor miracle.
Since it is highly doubtful that I will ever be able to document the effects of this protocol with a prospective, randomized, double-blinded and placebo-controlled clinical trial, I decide to share it will all who might be interested. It is now the focus of my next new book since the magnesium book has now been completed. I would strongly recommend adding this Gut Reboot Protocol to any treatment protocol for any condition. Also, I would welcome feedback from anyone who uses this protocol. Email: email@example.com
Diseases Associated with Unhealthy Gastrointestinal Microbiomes
- Leaky gut (basic foundation for everything else listed below) [4,5]
- General impairment/negative modulation of immune function 
- Breast cancer 
- Pancreatic cancer [8,9]
- Colorectal cancer 
- Metabolic syndrome 
- Heart disease and heart failure 
- High blood pressure 
- Gestational diabetes 
- Multiple complications of pregnancy 
- Allergic diseases and food allergies [16,17]
- Autoimmune thyroid disease 
- Polycystic ovary syndrome 
- Migraine 
- Depression 
- Autism and autism spectrum disorder 
- Abnormal mental health in adolescents 
- Decreased cognitive function and memory 
- Parkinson’s disease and neurodegenerative diseases in general 
- Stroke and other central nervous system diseases 
- Irritable bowel syndrome 
- Inflammatory bowel disease and intestinal fibrosis 
- Abnormal bile acid profiles 
- Liver disease [30,31]
- Bacterial vaginosis 
- Mucositis from chemotherapy and/or radiotherapy 
- Diabetes mellitus and abnormal lipid profiles [34,35]
- Juvenile idiopathic arthritis 
- General arthritic conditions3 
- Rheumatic diseases 
- Gastrointestinal conditions in genera 
- Idiopathic pulmonary fibrosis and other interstitial lung diseases 
- Chronic obstructive pulmonary disease (COPD) 
- Asthma and cystic fibrosis 
- Eye diseases [43,44]
- Ongoing support of periodontitis and gingivitis [45-47]
- Gastrointestinal chronic pathogen colonization (CPC) in asymptomatic kidney transplant patients 
- Abnormal gut microbiome secondary to antibiotic exposure 
- Obesity and weight gain [50-53]
(To access abstracts and some full-length articles, type in PMID number on the PubMed website in the Search box: https://www.ncbi.nlm.nih.gov/pubmed)
8. Pushalkar S, Hundeyin M, Daley D et al. (2018) The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discovery 8:403-416. PMID: 29567829
14. Zhang J, Ma S, Wu S et al. (2019) Effects of probiotic supplement in pregnant women with gestational diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Journal of Diabetes Research 2019:5364730. PMID: 31583250
17. Santos S, Konstantyner T, Cocco R (2019) Effects of probiotics in the treatment of food hypersensitivity in children: a systematic review. Allergologia et Immunopathologia Aug 30 [Epub ahead of print]. PMID: 31477401
21. Zheng P, Zeng B, Zhou C et al. (2016) Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism. Molecular Psychiatry 21:786-796. PMID: 27067014
32. Li C, Wang T, Li Y et al. (2019) Probiotics for the treatment of women with bacterial vaginosis: a systematic review and meta-analysis of randomized clinical trials. European Journal of Pharmacology Sep 25 [Epub ahead of print]. PMID: 31562865
35. Tiderencel K, Hutcheon D, Ziegler J (2019) Probiotics for the treatment of type 2 diabetes: a review of randomized controlled trials. Diabetes/Metabolism Research and Reviews Aug 29 [Epub ahead of print]. PMID: 31465625
37. Costello M, Robinson P, Benham H, Brown M (2015) The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis. Best Practice & Research. Clinical Rheumatology 29:202-212. PMID: 26362739
40. Salisbury M, Han M, Dickson R, Molyneaux P (2017) The microbiome in interstitial lung disease: from pathogenesis to treatment target. Current Opinion in Pulmonary Medicine 23:404-410. PMID: 28650861
45. Cantore S, Ballini A, De Vito D et al. (2018) Clinical results of improvement in periodontal condition by administration of oral probiotics. Journal of Biological Regulators and Homeostatic Agents 32:1329-1334. PMID: 30334434
46. Inchingolo F, Dipalma G, Cirulli N et al. (2018) Microbiological results of improvement in periodontal condition by administration of oral probiotics. Journal of Biological Regulators and Homeostatic Agents 32:1323-1328. PMID: 30334433
47. Soares L, Carvalho E, Tinoco E (2019) Clinical effect of Lactobacillus on the treatment of severe periodontitis and halitosis: a double-blinded, placebo-controlled, randomized clinical trial. American Journal of Dentistry 32:9-13. PMID: 30834725
48. Westblade L, Satlin M, Albakry S et al. (2019) Gastrointestinal pathogen colonization and the microbiome in asymptomatic kidney transplant recipients. Transplant Infectious Disease Sep 10 [Epub ahead of print]. PMID: 31502737
49. Yallapragada S, Nash C, Robinson D (2015) Early-life exposure to antibiotics, alterations in the intestinal microbiome, and risk of metabolic disease in children and adults. Pediatric Annals 44:e265-e269. PMID: 26587819
51. Crovesy L, Ostrowski M, Ferreira DMTP et al. (2017) Effect of Lactobacillus on body weight and body fat in overweight subjects: a systematic review of randomized controlled clinical trials. International Journal of Obesity 41:1607-1614. PMID: 28792488
52. Menni C, Jackson M, Pallister T et al. (2017) Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain. International Journal of Obesity 41:1099-1105. PMID: 28286339
53. Seganfredo F, Blume C, Moehlecke M et al. (2017) Weight-loss interventions and gut microbiota changes in overweight and obese patients: a systematic review. Obesity Reviews 18:832-851. PMID: 28524627
58. Richenbacher O, Filippi C, Zurcher A, Filippi A (2019) Acceptance of a tongue vacuum cleaner among children and evaluation of tongue cleaning at home. Swiss Dental Journal 129:102-107. PMID: 30647023
59. Gao L, Liu P, Song J (2010) [Relationship between tongue presentations and serum level of C-reactive protein in patients with acute cerebral infarction]. Article in Chinese. Chinese Journal of Integrated Traditional and Western Medicine 30:1146-1148. PMID: 21275163
60. Pedrazzi V, Sato S, de Mattos Mda G et al. (2004) Tongue-cleaning methods: a comparative clinical trial employing a toothbrush and a tongue scraper. Journal of Periodontology 75:1009-1012. PMID: 15341360
61. Outhouse T, Fedorowicz Z, Keenan J, Al-Alawi R (2006) A Cochrane systematic review finds tongue scrapers have short-term efficacy in controlling halitosis. General Dentistry 54:352-360, 367-368. PMID: 17004573
63. Amou T, Hinode D, Yoshioka M, Grenier D (2014) Relationship between halitosis and periodontal disease-associated oral bacteria in tongue coatings. International Journal of Dental Hygiene 12:145-151. PMID: 23890391
67. Guo Q, Wu Q, Bai D et al. (2016) Potential use of dimethyl sulfoxide in treatment of infections caused by Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 60:7159-7169. PMID: 27645245
69. Yahya M, Alias Z, Karsani S (2018) Antibiofilm activity and mode of action of DMSO alone and its combination with afatinib against Gram-negative pathogens. Folia Microbiologica 63:23-30. PMID: 28540585
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