Homeopathy and the Microbiome the Key to Lyme and Other Chronic Diseases

Homeopathy and the Microbiome The key to Lyme and other chronic diseases

Ronald D. Whitmont, MD, President, The American Institute of Homeopathy Clinical Assistant Professor, Family and Community Medicine New York Medical College

Discussion Goals

• Human Microbiome • Chronic Inflammatory Disease • An Example of Chronic Lyme Disease • Homeopathy

The Human Microbiome Microbiome

• Ecology and symbiosis • Fundamental to health • Dysbiosis associated inflammation Ecological Complexity

Metagenomic studies reveal that the human microbiome is comprised of an exceedingly complex group of different ecological niches existing throughout the body

Nature. 2007 Oct 18; 449(7164): 804–810. The human microbiome project: exploring the microbial part of ourselves in a changing world. Turnbaugh PJ, Ley RE, Hamady M, et al. DOI: 10.1038/nature06244

Supra-Organism

– A symbiosis between human and microbial organisms – Collective Interdependency

Medical Hypotheses. 74(2),2010:214215. The human superorganism – Of microbes and men. Sleator RD. (Ed) DOI: 10.1016/j.mehy.2009.08.047

Supra-Organism

A continuous spectrum of different ecosystems dependent on: – Diversity – Ecology – Symbiosis

Genome Biology 201314:R1. Biogeography of the ecosystems of the healthy human body. Zhou Y, Gao H, Mihindukulasuriya KA, et al. DOI: 10.1186/gb-2013-14-1-r1

The Human Microbiome

• Complementary to the human genome

• Neither functions independently

Nature. 2007 Oct 18; 449(7164): 804–810. The human microbiome project: exploring the microbial part of ourselves in a changing world. Turnbaugh PJ, Ley RE, Hamady M, et al. DOI: 10.1038/nature06244

1 Gram of Healthy Human

Stool • 100 Billion Bacteria • 100 Million Viruses • 100 Million Archaea • 10 Million Human Cells • 1 Million Fungal Spores

PLOS Biology. http://dx.doi.org/10.1371/journal.pbio.1002503 Fecal Transplants: What Is Being Transferred? Bojanova DP, Bordenstein SR.

The Human Microbiome

Function integral to: • Nutrition • Development • Immunity • Mental and Physical Health

PLOS/One: June 13, 2012. Analyses of the Microbial Diversity across the Human Microbiome. Li K, Bihan M, Yooseph S, et al. DOI: 10.1371/journal.pone.0032118

The Human Microbiome

Regulates development and function of the immune system

Cell Host & Microbe. Control of Brain Development, Function, and Behavior by the Microbiome. Sampson TR, Mazmanian SK. DOI: 10.1016/j.chom.2015.04.011

Colonization

Begins before birth in the placenta

Science Translational Med 21 May 2014;6(237): 237ra65 The Placenta Harbors a Unique Microbiome. Aagaard K, Ma J, Antony KM, et al. DOI: 10.1126/scitranslmed.3008599. Most Critical Period

Before birth until two years of life

Nutr.Reviews;65(6):259- 299. Perinatal and Neonatal Manipulation of the Intestinal Microbiome: a Note of Caution. Neu J. DOI: 10.1111/j.1753- 4887.2007.tb00305.x Diversity of Microbiome

Determined by Environment:

• Maternal Microbiome • Birth Process • Medication History

Medication Damage

• Antibiotics, antifungals, antivirals • PPI’s • Glucocorticosteroids? Antihistamines? • SSRI’s? HRT? Chemotherapy? • Immunosuppressant's? Vaccines? Antibiotics

• Disrupt ecology of microbiome – Overgrowth of resistant organisms – Inhibition and elimination of sensitive organisms

Science 2012; 336(6086):1255-1262. The Application of Ecological Theory Toward an Understanding of the Human Microbiome. Costello EK, Stagaman K, Dethlefsen L. DOI: 10.1126/science.1224203 Antibiotics

Promote fungal (viral?) overgrowth

Infect Immune 2004;72(9): 4996–5003. Role of Antibiotics and Fungal Microbiota in Driving Pulmonary Allergic Responses. Noverr MC, Noggle RM, Toews GB, et al. DOI: 10.1128/IAI.72.9.4996-5003.2004

Antibiotics and Asthma

Maternal antibiotic use in pregnancy associated with 89% increased risk of childhood asthma (p<0.0001)

Medscape Ob/Gyn Women’s Health November 27, 2016 Coverage from the American College of Allergy, Asthma & Immunology (ACAAI) 2016 Annual Scientific Meeting. http://www.medscape.com/viewarticle/872028?nlid=110951_25 81&src=WNL_mdplsnews_161202_mscpedit_obgy&uac=2427 86PX&spon=16&impID=1245995&faf=1

Asthma and Antibiotics in the First Year of Life

• 1-2 Courses  20% increased risk • 3-4 Courses  30% increased risk • > 4 Courses  50% increased risk

Chest 2007;131(6):1753-9. Increased risk of childhood asthma from antibiotic use in early life. Kozyrskyj AL, Ernst P, Becker AB. DOI: 10.1378/chest.06-3008

Asthma and Antibiotics in the First Year of Life

• Risk of asthma was highest in children receiving more than four courses of antibiotics • Broad-spectrum cephalosporin use was more common in these subpopulations of children

Chest. 2007;131(6):1753-9. Increased risk of childhood asthma from antibiotic use in early life. Kozyrskyj AL, Ernst P, Becker AB DOI: 10.1378/chest.06-3008

Antibiotics and Asthma

• Adjusted odds ratio of 4.05 if ABX used in 1st year of life • Adjusted odds ratio of 1.64 if ABX used after 1st year of life

Clinical & Experimental Allergy;29,(6)1999:766–771. Antibiotic use in early childhood and the development of asthma. Wickens, Pearce, Crane, et al. DOI: 10.1046/j.1365-2222.1999.00536.x

“Over the past four decades, there has been a significant increase in allergy and asthma in westernized countries, which correlates with alterations in fecal microbiota (microflora) and widespread use of antibiotics”

Infect Immune 2004;72(9): 4996–5003. Role of Antibiotics and Fungal Microbiota in Driving Pulmonary Allergic Responses. Noverr MC, Noggle RM, Toews GB, et al. DOI: 10.1128/IAI.72.9.4996-5003.2004

Pediatrics

Prevalence of many chronic diseases, including Asthma has tripled since 1980

MMWR Surveillance for Asthma -- United States, 1960-1995 Mannino DM, Homa DM, Pertowski CA. https://www.cdc.gov/mmwr/preview/mmwrhtml/00052262.htm

Asthma • The leading cause of chronic illness in U.S. children • One of the fastest growing chronic conditions in developed nations

Population Reference Bureau. Childhood Asthma: A Growing American Epidemic Carlson JE, Stroebel C. http://www.prb.org/Publications/Articles/2001/ChildhoodAsthm aAGrowingAmericanEpidemic.aspx Asthma Between 1980-1994: • The total number of affected children increased by 75% • In children younger than 4 years, it increased by 160%

Population Reference Bureau. Childhood Asthma: A Growing American Epidemic. Carlson JE, Stroebel C. http://www.prb.org/Publications/Articles/2001/ChildhoodAsthmaAGrowingAmerica nEpidemic.aspx Asthma

A chronic dysbiosis of the respiratory tract

Lancet. 2014; 384 (9944):691–702. The role of the microbiome in exacerbations of chronic lung diseases. Dickson RP, Martinez FJ, Huffnagle GB. DOI: http://dx.doi.org/10.1016/S0140-6736(14)61136-3

Asthma “Respiratory tract dysbiosis provokes a dysregulated host immune response, which in turn alters growth conditions for microbes in airways, promoting further dysbiosis and perpetuating a cycle of inflammation and disordered microbiota”

Lancet. 2014; 384 (9944):691–702. The role of the microbiome in exacerbations of chronic lung diseases. Dickson RP, Martinez FJ, Huffnagle GB. DOI: http://dx.doi.org/10.1016/S0140-6736(14)61136-3

Dysbiosis

• The opposite of Symbiosis • An ecological imbalance between organisms within the ecology of the microbiome • Inversely proportional to diversity

Altern Med Rev 2004;9(2):180-197. The Causes of Intestinal Dysbiosis: A Review. Hawrelak JA, Myers SP.

Dysbiosis

• Can occur anywhere on body • Directly proportional to inflammation

Therapeutic Advances in Gastroenterology May 2013; 6(3):215-229. Microbial dysbiosis and colon carcinogenesis: could colon cancer be considered a bacteria-related disease? Sobhani I, Amiot A, Le Baleur Y.

Dysbiosis

• Acute: Triggers an adaptive immune inflammatory response (UTI, URI, Sinusitis, etc)

• Chronic: Drives chronic inflammatory diseases (IBD, Asthma, CAD, DM, etc)

Gastroenterol Int. 1998;11:29-30. Antibiotic impact on intestinal microflora. Gismondo MR.

Diversity

“Dictates the stability of ecosystems”

• Microbiome is an ecosystem

Science 06 July 2007. Stability and Diversity of Ecosystems. Ives AR, Carpenter SR. Diversity in the Gut

“Rich, balanced and diverse bacterial communities seem to be perceived as “self” and induce a quick maturation of the immune system and gut responses”

Immunity; 41(1) 2014:152–165. Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis Kawamoto S, Maruya M, Kato LM. DOI: 10.1016/j.immuni.2014.05.016 Diversity in the Gut

“Poor and unbalanced bacterial communities are apparently perceived as “non-self” and induce inflammatory responses aimed at eliminating it”

• Diversity inversely related to inflammation • Lack of diversity (dysbiosis) associated with high levels of inflammation

Immunity; 41(1), 2014:152–165. Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis Kawamoto S, Maruya M, Kato LM. DOI: 10.1016/j.immuni.2014.05.016 There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra- intestinal disorders.

Microbial Ecology in Health & Disease 2015, 26:26191 Dysbiosis of the gut microbiota in disease. Carding S, Verbeke K, Vipond DT, et al. DOI: 10.3402/mehd.v26.26191

Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease

Microbial Ecology in Health & Disease 2015, 26:26191 Dysbiosis of the gut microbiota in disease. Carding S, Verbeke K, Vipond DT, et al. DOI: 10.3402/mehd.v26.26191

Extra-intestinal disorders include allergy, asthma, metabolic syndrome, chronic fatigue, cardiovascular disease, autoimmune disorders, and obesity

Microbial Ecology in Health & Disease 2015, 26:26191 Dysbiosis of the gut microbiota in disease. Carding S, Verbeke K, Vipond DT, et al. DOI: 10.3402/mehd.v26.26191

Diversity

Diversity of the microbiome depends on an integrated ecology of bacteria, viruses, archaea, fungi and “parasites”

Parasites and Inflammation

Eradication of malaria in an otherwise stable population induces the emergence of autoimmunity

Emerg Infect Dis. Program to eradicate malaria in Sardinia, 1946–1950. Tognotti E. 2009 Sep. http://wwwnc.cdc.gov/eid/article/15/9/08-1317 DOI: 10.3201/eid1509.081317.

Sardinia, Italy

Between 1946–1950, the Rockefeller Foundation conducted a large-scale Malaria eradication Project

Emerg Infect Dis. Program to eradicate malaria in Sardinia, 1946–1950. Tognotti E. 2009 Sep. http://wwwnc.cdc.gov/eid/article/15/9/08-1317 DOI: 10.3201/eid1509.081317.

Sardinia, Italy

267 metric tons of DDT were spread over the island which entirely eliminated Malaria

Emerg Infect Dis. Program to eradicate malaria in Sardinia, 1946–1950. Tognotti E. 2009 Sep. http://wwwnc.cdc.gov/eid/article/15/9/08-1317 DOI: 10.3201/eid1509.081317.

Cases of malaria, by year, Sardinia, 1946–1952

Malaria Cases in Sardinia

Year No. cases (relapses) 1946 74,641

1947 39,303

1948 15,121

1949 1,314

1950 0 (44)

1951 9 (8)

1952 0

Incidence of Multiple Sclerosis, Sardinia, Italy

• 0 before 1950 • 1.1/100,000 in 1965-69 • 5.8/100,000 in 1995-99

Neuroepidemiology. 2005;25(3):129-34. Increasing incidence of multiple sclerosis in the province of Sassari, northern Sardinia. Pugliatti M, Riise T, Sotgiu MA, et al. DOI: 10.1159/000086677

Incidence of Multiple Sclerosis, Sardinia, Italy

• 9.7/100,000 in 2003-07

Mult Scler 2011;17(11):1282-9. Epidemiology of multiple sclerosis in south-western Sardinia. Cocco E, Sardu C, Massa R, et al. DOI: 10.1177/1352458511408754

Current Prevalence of Multiple Sclerosis

• 224/100,000 in Sardinia • 90/100,000 in U.S.

PLOS One 2012; Population Based Study of 12 Autoimmune Diseases in Sardinia, Italy: Prevalence and Comorbidity. Sardu C, Cocco E, Mereu A. DOI: 10.1371/journal.pone.0032487

Sardinia, Italy

“A dramatically rapid change of the environment after the eradication of malaria has led the Sardinian immune system to abnormal responses… favoring increased MS incidence over the last four decades in Sardinia because of the eradication of malaria, 50 years ago.”

Medical Hypotheses 2008; 70(4):819-25. Hygiene hypothesis: Innate immunity, malaria and multiple sclerosis. Sotgiu S, Angius A, Embry A, et al. DOI: 10.1016/j.mehy.2006.10.069 Sardinia, Italy

Eliminating a stable/commensal parasite from the environment alters the microbiome (and the immune system) and allows the phenotypic penetration of a disease of immune dysfunction

Medical Hypotheses 2008; 70(4):819-25. Hygiene hypothesis: Innate immunity, malaria and multiple sclerosis. Sotgiu S, Angius A, Embry A, et al. DOI: 10.1016/j.mehy.2006.10.069 Microbiome and Environment

Rapid environmental changes destabilize the microbiome, triggering dysbiosis and altering inflammatory patterns

EMBO Rep. 2012 Nov; 13(11): 968–970. The inflammation theory of Immunity; 41(1) 2014:152–165. Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis Kawamoto S, Maruya M, Kato LM. DOI: 10.1016/j.immuni.2014.05.016 Implications

The functioning of both the innate and adaptive immune systems are dependent on and programmed by the diversity the microbiome

Cell 2005;122(1):107-18. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Mazmanian SK, Liu CH, Tzianabos AO. DOI: 10.1016/j.cell.2005.05.007.

Alterations of microbiome (bacteria, viruses, fungi, archaea and parasites) have profound effects on immune system: • Risk of allergies, inflammation, autoimmunity and neoplasm

Cell 2005;122(1):107-18. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Mazmanian SK, Liu CH, Tzianabos AO. DOI: 10.1016/j.cell.2005.05.007.

One of the Most Important Causes of Dysbiosis “We’ve just spent the better part of a century doing our unwitting best to wreck the human- associated microbiota with a multifronted war on bacteria and a diet notably detrimental to its well-being.”

Gastroenterol Int. 1998;11:29-30. Antibiotic impact on intestinal microflora. Gismondo MR.

NYTimes Magazine. May 19, 2013:36-43,50,58-59. Some of My Best Friends are Bacteria. Pollan M.

“We have to stop looking at medicine as a war between invading pathogens and our bodies.”

New Yorker Magazine. Oct 22, 2012:39-39. Germs are Us. Interview with David A. Relman, Chief of Infectious Diseases VA Hospital Palo Alto, CA. Specter M. The germ theory of disease… is a gross “oversimplification”

The Lancet; 291(7551):1077-1081. Limitations of the Germ Theory. Stewart T, Path FC. DOI: 10.1016/S0140-6736(68)91425-6

Germ Theory

Disrupts Ecology of Supraorganism:

Trends Ecol Evol 2011;26(4):202-9. New paradigms for the evolution of beneficial infections. Sachs JL, Essenberg CJ, Turcotte MM. DOI: 10.1016/j.tree.2011.01.010 Germ Theory

Ignores Role of Immune System: – In resolving infection – In utilizing inflammation

Trends Ecol Evol 2011;26(4):202-9. New paradigms for the evolution of beneficial infections. Sachs JL, Essenberg CJ, Turcotte MM. DOI: 10.1016/j.tree.2011.01.010 Germ Theory

Neglects Role of Microbiome: – Evolutionary basis of Supraorganism – Complement to immune system

Trends Ecol Evol 2011;26(4):202-9. New paradigms for the evolution of beneficial infections. Sachs JL, Essenberg CJ, Turcotte MM. DOI: 10.1016/j.tree.2011.01.010 “It goes against dogma to think that bacteria would make our immune systems function better... But the picture is getting very clear: the driving force behind the immune system are commensals.”

Scientific American. June 2012:37-43. The Ultimate Social Network. Ackerman J. Infections

Play an important role in: • Immune system development • Microbiome diversity . Modulation of inflammation

Annu Rev Immunol. 2012; 30: 759–795. The Microbiome in Infectious Disease and Inflammation. Honda K, Littman DR DOI: 10.1146/annurev-immunol-020711-074937.

-Review-

The Human Microbiome

• The Microbiome is made up of a continuous interconnected geography of ecological niches covering the entire human organism

• Vital to growth, development and immune system functioning

Dysbiosis equals inflammation

Cell 2005;122(1):107-18. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Mazmanian SK, Liu CH, Tzianabos AO. DOI: 10.1016/j.cell.2005.05.007.

One of the most important causes of dysbiosis and inflammation results from the application of modern Germ Theory in medicine Chronic Disease

Chronic Disease

The Leading Cause of Death and Disability in the US

http://www.cdc.gov/chronicdisease/overview/

Chronic Disease “The great epidemic of our times, responsible for 75% of total health care costs and the majority of deaths in the US.”

Am J Med, 2015; 128(4):337–343 Health Care 2020: Reengineering Health Care Delivery to Combat Chronic Disease. Milani, RV, Lavie CJ. DOI: http://dx.doi.org/10.1016/j.amjmed.2014.10.047

Chronic Disease

• About half of all adults—117 million people—had one or more chronic health conditions in 2012 • 25% had two or more chronic health conditions

Prev Chronic Dis 2014;11:130389. Multiple chronic conditions among US adults: a 2012 update. Ward BW, Schiller JS, Goodman RA. DOI: 10.5888/pcd11.130389

Chronic Diseases

• Hypertension • coronary heart disease • Stroke • Diabetes • Cancer • Arthritis • Hepatitis • Kidneys disease • Asthma • COPD

“Causes” of Chronic Disease

-Lack of Physical Exercise -Hypertension -Hyperlipidemia -Poor Nutrition -Tobacco Use -Excessive Alcohol Use www.cdc.gov/chronicdisease/overview/

Chronic Disease

Common denominator:

Chronic Inflammation-Dysbiosis The Human Microbiome

EMBO Rep. 2012 Nov; 13(11): 968–970. The inflammation theory of disease. The growing realization that chronic inflammation is crucial in many diseases opens new avenues for treatment. Hunter P. DOI: 10.1038/embor.2012.142 Chronic Disease

“Inflammation has long been a well-known symptom of many infectious diseases, but molecular and epidemiological research increasingly suggests that it is also intimately linked with a broad range of non- infectious diseases, perhaps even all of them.”

“It is becoming increasingly evident that the lack of exposure to a variety of microorganisms, especially during early life, may result in the development of diseases such as type 1 diabetes, asthma, allergies, celiac disease, inflammatory bowel disease and obesity.”

J Perinatology (2011) 31, S29–S34; The developing intestinal microbiome and its relationship to health and disease in the neonate. Torrazza RM, Neu J. DOI:10.1038/jp.2010.172.

Chronic Disease

According to the ‘hygiene hypothesis’, the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both autoimmune and allergic diseases.

Clin Exp Immunol. 2010 Apr; 160(1): 1–9. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Okada H, Kuhn C, Feillet H, et al. DOI: 10.1111/j.1365-2249.2010.04139.x

Chronic Disease

Inversely related to the incidence of infectious disease

Clin Exp Immunol. 2010 Apr; 160(1): 1–9. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update. Okada H, Kuhn C, Feillet H, et al. DOI: 10.1111/j.1365-2249.2010.04139.x

Chronic Disease

• Epidemic and Increasing • Related to Dysbiosis and Microbiome damage • A result of chronic inflammation

Chronic Lyme Disease Chronic Lyme Disease

A chronic inflammatory condition, a dysbiosis Chronic Lyme Disease

• A diagnosis often based solely on clinical judgment rather than on well-defined clinical criteria and validated laboratory studies • AKA: Post Lyme Disease Syndrome

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease

A diagnostic term used in North America and Europe for patients with persistent pain, neurocognitive symptoms, fatigue, or all of these symptoms, with or without clinical or serologic evidence of previous early or late Lyme disease

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease

Despite resolution of the objective manifestations of infection after antibiotic treatment of Lyme, a minority of patients develop fatigue, musculoskeletal pain, difficulties with concentration or short-term memory, or all of these symptoms.

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease

Once the diagnosis is made, patients are commonly treated for months to years with multiple antimicrobial agents

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease No significant difference in clinical responses between those who received intravenous and oral antibiotics for 90 days and those who received placebo

N Engl J Med 2001; 345:85-92. Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease. Klempner MS, Hu LT, Evans J, et al. DOI: 10.1056/NEJM200107123450202 Chronic Lyme Disease IV ceftriaxone therapy results in short-term cognitive improvement for patients with post- treatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued

Neurology 2008; 70(13): 992-1003. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Fallon BA, Keilp JG, Corbera KM,et al. DOI: 10.1212/01.WNL.0000284604.61160.2d Chronic Lyme Disease There is substantial risk, with little or no benefit, associated with additional antibiotic treatment for patients who have long-standing subjective symptoms after appropriate initial treatment for an episode of Lyme disease

N Engl J Med 2007;357:1422-1430. A Critical Appraisal of “Chronic Lyme Disease”. Feder HM, Johnson BJB, O'Connell S. DOI: 10.1056/NEJMra072023 Chronic Lyme Disease

Antibiotic therapy causes considerable harm to patients treated for chronic Lyme disease or post–Lyme disease symptoms

Clin Infect Dis 2006;43:1089-1134. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Wormser GP, Dattwyler RJ, Shapiro ED, et al. Antibiotics

Impair immune system

Trends in Immunology;33(9), September 2012:459–466. Antibiotics, microbiota, and immune defense. Ubeda C, Pamer EG.

Antibiotics “Affect various host immune responses adversely… including leukocyte chemotaxis, lymphocyte and monocyte transformation, antibody production, phagocytosis, and the microbicidal action of polymorphonuclear leukocytes.”

Goodman and Gilman's The Pharmacological Basis of Therapeutics, 7th Edition. Gilman AG, Goodman LS, Rall TW, et al. MacMillan Publishing Co, N.Y.1985:1084. Antibiotics

Temporarily suppress acute inflammation via non- antimicrobial effects

Europ J Pharmacol.. Anti-inflammatory effects of macrolide antibiotics. Čulić O, Eraković V, Parnham MJ DOI: 10.1016/S0014-2999(01)01321-8

Antibiotics

• Worsen dysbiosis • Favor chronic inflammation

Gastroenterol Int. 1998;11:29-30. Antibiotic impact on intestinal microflora. Gismondo MR.

Chronic Lyme

Most cases of are remarkable for histories of repeated and prolonged overuse of antibiotics anteceding the acquisition of Lyme by many years, often beginning in early childhood

Clinical Observation: Whitmont, RD Chronic Lyme

Most cases demonstrate a downward spiral of worsening clinical symptomatology, directly proportional to the frequency (and length) of antibiotic therapy

Clinical Observation: Whitmont, RD Chronic Lyme

Risk of co-infections increases proportionally with duration of antibiotic use

Clinical Observation: Whitmont, RD Etiology?

Chronic Inflammation Chronic dysbiosis Microbiome

“Solutions?”

• Long-term antibiotics • Probiotics • Suppression of inflammation • Dump Germ Theory-Shift Paradigm Homeopathy Homeopathy • A 200 year old form of alternative Medicine • Currently used by more than 500 million worldwide • A form of Nanomedicine

Frontiers in Bioscience 2013;5(2):685-708. Adaptive network nanomedicine: an integrated model for homeopathic medicine. Bell I.

“Ironically, one of the most controversial systems of alternative medicine, homeopathy, could turn out to be one of the oldest and demonstrably safest forms of nanoparticle based treatment already used worldwide for infectious diseases.”

Eur J Integr Med 2013;5(2):126-40. Advances in Integrative Nanomedicine for Improving Infectious Disease Treatment in Public Health. Bell IR, Schwartz GE, Boyer NN, et al. DOI: 10.1016/j.eujim.2012.11.002

Homeopathy

Historically interpreted within a vitalistic and spiritual conceptual framework common in the 18th Century

The Organon of Medicine, 6th Ed. 1842. Hahnemann SC,

Homeopathy

A form of:

Adaptive Network Nanomedicine

Frontiers in Bioscience. Adaptive network nanomedicine: an integrated model for homeopathic medicine. 2013;5(2):685- 708. Bell I, Schwartz GE. Homeopathy Using Transmission Electron Microscopy (TEM), electron diffraction and chemical analysis by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES), the presence of physical entities in extreme homeopathic dilutions, in the form of nanoparticles of the starting metals and their aggregates, has been confirmed

Homeopathy 2010;99(4):231-242. Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective. Chikramane PS, Suresh AK, Bellare JR, et al. DOI: 10.1016/j.homp.2010.05.006

Homeopathy Medicines in high potencies (30c and 200c) involving huge dilution factors (1060 and 10400 respectively) are many orders of magnitude greater than Avogadro’s number, and theoretically should not contain measurable remnants of the starting materials

Homeopathy 2010;99(4):231-242. Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective. Chikramane PS, Suresh AK, Bellare JR, et al. DOI: 10.1016/j.homp.2010.05.006

Homeopathy

Observable nanoparticle forms of source material (and silica) exist in all homeopathic potencies

Int J High Dilution Res. 2011;10:299-310. Homeopathy emerging as nanomedicine. Upadhyay RP, Nayak C. Nanoparticles

• Measure from 1-100 nm in diameter • Formed by: – Top-down milling from source material – Bottom-up self-assembly

Advanced Drug Delivery Rev 2011;63:427-40. Nanosizing for oral and parenteral drug delivery: a perspective on formulating poorly-water soluble compounds using wet media milling technology. Merisko-Liversidge E, Liversidge GG. Nanoparticles

Exhibit superior antioxidant properties than their respective bulk forms

J Agricult Food Chem 2012;60(21):5388-99. Antioxidant activities of curcumin and ascorbyl dipalmitate nanoparticles and their activities after incorporation into cellulose-based packaging films. Sonkaew P, Sane A, Suppakul P.

Nanoparticles

More effective drug delivery vehicles than conventional bulk form drugs • Reach selective targets more efficiently • Reduce total dosage needed • Cross Blood-Brain Barrier

Current Drug Deliv 2010;7:303-11. Nanoparticles: a promising therapeutic approach in atherosclerosis. Antoniades C, Psarros C, Tousoulis D, et al.

Nanomedicine

Distinct advantages: • Targets specific cells • Doses last longer • Therapeutic effects are magnified (up to 1000 times)

Autoimmunity 2009;42:368-72. Imaging inflammation in real time- future of nanoparticles. Hueber AJ, Stevenson R, Stokes RJ, et al. Nanoparticles Multiple selective effects: • Apoptosis • Anti-inflammatory • Antioxidant • Immunomodulatory • Bacterial, viral, fungal infectivity

PLoS ONE 2011 ;6e26684. PLGA, PLGA-TMC and TMC-TPP nanoparticles differentially modulate the outcome of nasal vaccination by inducing tolerance or enhancing humor immunity. Keijzer C, Slutter B, van der Zee R, et al. Nanoparticles

• Reduce side effects • Greater efficacy • Lower costs

Methods in Enzymology 2012;508:271-94. Nanotechnology as a promising strategy for alternative routes of insulin delivery. Reis CP, Damge C.

Nanoparticles • At high doses: – Trigger stronger pharmacological effects • At low doses: – Mobilize non-pharmacological, biological adaptation, hormesis and endogenous amplification mechanisms

Homeopathy, 99 (2010), pp. 231–242. Extreme homeopathic dilutions retain starting materials: a nanoparticulate perspective. Chikramane PS, Suresh AK, Bellare JR, et al. Nanomedicine • Supports the patient's adaptive networks leading to functional self reorganization as a biological network • Host expression of a more robust cellular defense system against infections and other stressors

European Journal of Integrative Medicine; 5(2):126–140. Advances in integrative nanomedicine for improving infectious disease treatment in public health. Bell IR, Schwartz GE, Boyer NN. DOI: 10.1016/j.eujim.2012.11.002.

Homeopathy • The world’s oldest form of clinical nanomedicine • Thousands of published case studies in worldwide database • Demonstrated effectiveness in a wide range of acute, chronic and infectious conditions Plasmodium Malaria

Significant inhibitory effects on parasite multiplication in vivo

Homeopathy 2006;95:223-228. Effects of homeopathic medications Eupatorium perfoliatum and Arsenicum alabum on parasitemia of Plasmodium berghei-infected mice. Lira-Salazar G, Marines-Montiel E, Torres-Monzon J, et al. DOI: 10.1016/j.homp.2006.06.003

Antiviral Effects Significant reductions of infectivity in: – Human herpesvirus 1, Human adenovirus C serotype 5, Influenza A virus, Human respiratory syncytial virus, Human parainfluenza virus 3, Human rhinovirus B serotype 14, and Human coxsackievirus serotype A9

Can J Physiol Pharmacol 2007;85:1084-90. In vitro evaluation of the antiviral effects of the homeopathic preparation Gripp-Heel on selected respiratory viruses. Glatthaar-Saalmuller B. DOI: 10.1139/Y07-100

HIV/AIDS Significant improvement in specific physical, immunologic, neurologic, metabolic, and quality-of-life benefits, including: • Lymphocyte counts and functions • HIV viral loads in HIV/AIDS

J Alternat Complement Med 2003;9:133-41. Controlled clinical trials evaluating the homeopathic treatment of people with human immunodeficiency virus or acquired immune deficiency syndrome. Ullman D. DOI: 10.1089/107555303321223008

Homeoprophylaxis of

Leptospirosis

• N=2.3 million in high risk epidemic region

Homeopathy 2010;99:156-66. Large-scale application of highly-diluted bacteria for Leptospirosis epidemic control. Bracho G, Varela E, Fernandez R, et al. DOI: 10.1016/j.homp.2010.05.009

Leptospirosis • Significantly reduced incidence in intervention regions • Increased incidence in non- intervention regions • Incidence fell below historic median

Homeopathy 2010;99:156-66. Large-scale application of highly-diluted bacteria for Leptospirosis epidemic control. Bracho G, Varela E, Fernandez R, et al. DOI: 10.1016/j.homp.2010.05.009

Chronic Disease • 8 year follow-up cohort study • N=3709 • 97% Chronic Disease

BMC Public Health 2008;8:413-421. How healthy are chronically ill patients after eight years of homeopathic treatment? – Results from a long term observational study. Witt CM, Lüdtke R, Mengler N, et al. DOI:10.1186/1471-2458-8-413

Most frequent diagnoses:

– migraine, tension type headache, sleep disorders, depression, anxiety disorders, multiple eczemas, psoriasis, allergic dermatitis, allergic rhinitis, allergies, dysmenorrhea, multiple infections, hypertension, low back pain, asthma

Chronic Disease • Significant decreased severity (p < 0.001) • Physical and mental Quality of Life scores increased • Younger age, female gender and more severe disease at baseline were most predictive factors of therapeutic success

Homeopathy

• Adaptive Network Nanomedicine • Directly impacts microbiome

Homeopathy and the

Microbiome

“Homeopathic potencies are capable of completely altering the bacterial flora of the bowel, and this fact has been demonstrated in many hundreds of cases”

Br Hom J 1936;26:163-188. The Potentised Drug and its Action on the Bowel Flora. Paterson J.

Homeopathy and Lyme

Disease

“The judicious use of the classical homeopathic method has proven itself clinically effective in preventing and treating illnesses like Lyme disease in all its clinical stages.”

J Am Inst Homeopathy 1997;90(4) :186-198 Homeopathy and Lyme Disease. Whitmont RD.

A Case Report: Chronic Lyme Disease Dysbiosis

Initial Consultation:

A 92-year-old Caucasian male retired physician presented with complaints of “Chronic Lyme Disease”

Main Symptoms

• Multiple tick bites over previous year • Living in Lyme endemic region

Treatment History

• Initial Rx: Doxycycline 100mg POBID for 28 days, followed by Cefdinir 600mg POQD for an additional 26 days

• Initial improvement while being treated, followed by relapse and worsening symptoms shortly after discontinuing antibiotics

Organon

“These [treatments] likewise do nothing but debilitate, and only suppress or suspend the malady for a short time without being able to cure it, and when used for a long time always add a new morbid state to the old disease.”

Organon of Medicine, 6th Ed. 1842; Aphorism 39:123. Hahnemann SC,

Main Symptoms

• Brain fog • Depression • Vertigo: Worse after rising in the morning • Nausea with intolerance of spices and fatty foods • Prefers warm environments, fresh air • “Clicking” in neck • Night sweats • Fatigue: “great effort” to do deskwork. Has not gone outdoors in previous 2 months • Generalized Weakness with lack of energy

Medical History

• Multiple urinary complaints including chronic urinary retention, hesitancy, incontinence, nocturia • Recent UTI treated with Ciprofloxacin • Life-long history of frequent recurrent antibiotic use (at “any sign” of cold or infection) • IBS • Gastroparesis

Medical History

• Chronic recurrent sinusitis treated repeatedly with antibiotics • Hiatal hernia • Osteopenia

Medical History

• Degenerative Disc Disease (DDD) of Spine • Prostate cancer s/p radiation and chemotherapy • Abdominal Aortic Aneurism (AAA)

Physical Examination

• Tall, thin, frail Caucasian male • Appeared older than stated age • Pectus excavatum • Pale skin • No apparent distress • Vital signs and physical examination otherwise unremarkable and noncontributory

Diagnostic Assessment

Antibiotic overuse and abuse with evidence of chronic dysbiosis manifesting as: • IBS • Chronic sinusitis • Chronic Lyme/Post Lyme Syndrome

Dysbiosis leading to chronic malabsorbtion and malnutrition contributing to: • Osteopenia • Fatigue

Therapeutic Intervention

• Classically Prescribed Homeopathic Medicine, 200c • One Single Dry Dose By Mouth

Classical Homeopathic

Prescribing • Depends on the total clinical pattern of biopsychosocial symptoms • Relies on: – Individual salience – State dependency in the host to elicit beneficial rather than adverse effects

Global Advan Health Med 2014;3(1):36-53. Integrative Nanomedicine: Treating Cancer with nanoscale natural products. Bell I, Sarter B, Koithan M, et al. 1 Month Follow-up

• “Doing much better” • Nausea is “mild”, worse in morning after rising, better by noon • Vertigo only “once in a while”, usually with nausea. • Still Feels head isn’t “level”, not “even-keeled” • Nocturia “improved”

Therapeutic Intervention

• Classically Prescribed Homeopathic Medicine, 200c • One Single Dry Dose By Mouth

3 Month Follow-up

• “Very pleased over last 6 weeks” • Gradual improvement in energy • No nausea • No GI distension • No recurrent sinusitis or UTI

3 Month Follow-up

• No vertigo • No Brain fog • No more urinary incontinence • Asks: “How do you discourage old friends from staying too long?”

1 Year Follow-up

• No recurrence of symptoms • No repetition of medicine • Feels strong and fit

1 Year Follow-up

Patient Perspective:

“I’m doing very well for 94. I have no complaints. If I continue how I am I will be very satisfied.” -Review- Homeopathy

The oldest continuously utilized form of nanomedicine worldwide Homeopathy

A paradigm shift away from the “Germ Theory” Organon

“It was high time… to put a stop to these abominations, to command a cessation of these tortures… in place of curing patients, render them incurable by the addition of new, chronic medicinal maladies by means of the prolonged use of wrong, powerful medicines”

Organon of Medicine, 6th Ed. 1842: 79. Hahnemann SC. Homeopathy

Promotes: • Resolution of inflammation • Resolution of dysbiosis • Integration of immune system and microbiome • Restoration of health

Homeopathy

Effective in a wide range of clinical conditions including: – Acute and Chronic illness – Infections – Chronic Lyme Disease – Autoimmune Disease – Cancer

Homeopathy

Advantages: – Ecologically sustainable – Holistic – Compatible with microbiome – Compatible with immune system – Inexpensive

Conclusion…

The Human Microbiome: • The ecological foundation of healthy growth, development and functioning

The Epidemic of Chronic Illness: • An Iatrogenic side-effect of conventional medicine • A result of the Germ Theory

The Germ Theory: • Promotes microbiome and immune system damage, resulting in inflammation, dysbiosis • Should be 2nd line

Chronic Lyme Disease • A example of a chronic dysbiosis - inflammatory disease

Homeopathy: • A form of adaptive network nanomedicine • Demonstrated efficacy in treating (and preventing) acute, chronic and infectious diseases

Homeopathy: • Worldwide use • Well established time-honored methodology • Safe and effective

Data from the Human Microbiome Project provides a scientific imperative to utilize and further investigate homeopathy as nanomedicine “Rather than rejecting the entire filed of homeopathy for its originally vitalistic interpretations, it is time for modern scientists to examine seriously the nanomedicine implications of Hahnemann’s empirical findings for integrative health care.”