MYRTO ASHE, MD, MPH

HOW AND WHY PESTICIDES AFFECT OUR HEALTH

Linking diseases and

pesticides

There are many associations:•Pesticide applicators and cancer•Children of pesticide applicators and cancer•Pest strips, pet shampoos and cancer•Asthma•Obesity and diabetes•Birth defects•Autism, ADHD, and Parkinson’s disease

Childhood Cancer• The rate has been rising about 1% per year since the 1990s•What part of this is pesticides?

1990 1995 2000 2005 2010 20158000

8500

9000

9500

10000

10500

11000

Number of children diagnosed with cancer every year

Childhood Disabilities• From “The Future of Children” by Neal Halfon and others: most of this increase involves neurological/behavior abnormalities

1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 20100

1

2

3

4

5

6

7

8

9

% children with activity limitations due to disability

Asthma, child and adult

THE CHOICES

•Harmless

•Harmful and worth it

•Harmful and not worth it

“What we knew (for sure)”: 1940s TOXICOLOGY

•Fetus protected by placental barrier

•The more poison you use, the higher the death rate

•“The dose makes the poison”

•Biochemical elimination of toxins

The Placental Barrier• This was the main source of reassurance• But it’s not that helpful:

• Research examined the umbilical cord blood of 10 babies born in 2004• Found 287 chemicals• Each baby had about 200• 180 carcinogens• 208 known to cause birth defects• 217 toxic to the brain

Non-monotonic effects

Why it “just ain’t so”:2014 TOXICOLOGY

•The placental barrier not as strong as we thought

•Some chemicals have worse effects at small doses than at larger doses

•Chemicals in combination have effects that are multiplicative, not additive

Just as our understanding of toxicology has changed in the last 70 years,

so has our understanding of health and illness

2014 MEDICINE

•Beneficial bacteria

•Immune system/inflammation

•Gene expression

2014 MEDICINE

•Beneficial bacteria outnumber human cells 10 to 1

•Gut biome involved in detoxification, immunity, nutrition

•Chronic immune system activation causes disease

•Genes are expressed at times, suppressed at other times, in response to the environment

2014 MEDICINE•Beneficial bacteria outnumber human 10:1 cells

•The gut biome is involved in detoxification, immunity, nutrition

•Chronic immune system activation causes disease

•Genes are expressed at times, suppressed at other times, in response to the environment

Beneficial Bacteria Help us Detoxify

Proc Natl Acad Sci U S A. May 29, 2012; 109(22): 8364–8365.

Symbionts provide pesticide detoxificationJohn H. Werren1

Beneficial bacteria train and control

the immune systemNATURE | NEWS

Babies’ weak immune systems let good bacteria inResistance to infections is suppressedTo prevent inflammation frombacterial colonization.Sara Reardon

6 November 2013

2014 MEDICINE•Beneficial bacteria outnumber human 10:1 cells

•Gut biome involved in detoxification, immunity, nutrition

•Chronic immune system activation results in disease

•Genes are expressed at times, suppressed at other times, in response to the environment

2014 MEDICINE•Beneficial bacteria outnumber human 10:1, or much more, maybe 1000:1

•Gut biome involved in detoxification, immunity, nutrition

•Chronic immune system activation causes disease

•Genes are expressed at times, suppressed at other times, in response to the environment

Toxicology. 2013 May 10;307:35-41.

Epigenetics and pesticides.• Collotta M1, Bertazzi PA, Bollati V.

• Abstract

•[…] Epigenetics is the study of heritable changes in gene expression that occur without a change in the DNA sequence. [...]• We review current evidences indicating that epigenetic modifications may mediate pesticide effects on human health […]

Toxicology. 2013 May 10;307:35-41.

Epigenetics and pesticides.• Collotta M1, Bertazzi PA, Bollati V.

• Abstract

•[…] Epigenetics is the study of heritable changes in gene expression that occur without a change in the DNA sequence. [...]• We review current evidences indicating that epigenetic modifications may mediate pesticide effects on human health […]

SUMMARYDiseases that affect us depend on• which genes are expressed• which bacteria are thriving• how the genes and bacteria direct our immune system

A step furtherHow we think, feel, and act

depends on our environment and what our

bacteria think of our environment…

2014 PHYSIOLOGY

•The brain is full of immune cells

•Immune cells communicate with nerve cells

•If bacteria control the immune system, and the immune system has an impact on nerve cells…

• Trends Neurosci. 2013 May;36(5):305-12.

•Gut-brain axis: how the microbiome influences anxiety and depression.• Foster JA1, McVey Neufeld KA.

[…] New studies show that bacteria […] in the gastrointestinal (GI) tract can activate neural pathways and central nervous system signaling systems. […]

Brain Cells

Pesticides pose problems for developing brains

• Curr Opin Pediatr. 2008 Apr;20(2):191-7. • Pesticides and child neurodevelopment.• Rosas LG1, Eskenazi B.• SUMMARY:

•Given that the literature suggests a link between organochlorine and in-utero pesticide exposure and impaired child neurodevelopment, clinicians should educate parents about prevention of exposure, especially in populations living in agricultural areas or where household use is common.

Environ Health Perspect. Jul 2012; 120(7): 944–951.

Tipping the Balance of Autism Risk: Potential Mechanisms Linking Pesticides and AutismReviewJanie F. Shelton, 1 Irva Hertz-Picciotto,1,2 and Isaac N. Pessah2,3

Rise in Autism Rates

In autism, the brain is inflamed

Neuropsychopharmacology Reviews (2013) 38, 241–242;

Neuroinflammation and Autism: Toward Mechanisms and TreatmentsChristopher J McDougle1,2 and William A Carlezon Jr2,3

So what causes brain inflammation?

Microglia are activated by

body inflammation

Glia. 2013 Jan;61(1):71-90.

Microglia and neurodegeneration: the role of systemic inflammation.Cunningham C.

Do pesticides cause body inflammation?

Ecotoxicol Environ Saf. 2009 Oct;72(7):2025-32

Effect of pesticides on cell survival in liver and brain rat tissues.Astiz M1, de Alaniz MJ, Marra CA.

Pesticides are the main environmental factor associated with the etiology of human neurodegenerative disorders such as Parkinson's disease. Our laboratory has previously demonstrated that the treatment of rats with low doses of dimethoate, zineb or glyphosate alone or in combination induces oxidative stress (OS) in liver and brain[…]

Neuroinflammation in other

brain disordersJournal of Neuroinflammation 2013, 10:43 

Neuroinflammation and psychiatric illnessSouhel Najjar15*, Daniel M Pearlman25, Kenneth Alper4, Amanda Najjar3 and Orrin Devinsky145

Alzheimer’s DiseaseJ Alzheimers Dis. 2010;21(1):1-14. doi: 10.3233/JAD-2010-1414.

Neuroinflammation in Alzheimer's disease: mechanisms, pathologic consequences, and potential for therapeutic manipulation.Hensley K.

Parkinson’s Disease

Parkinsonism Relat Disord. 2012 Jan;18 Suppl 1:S210-2. doi: 10.1016/S1353-8020(11)70065-7.

Neuroinflammation in Parkinson's disease.Hirsch EC1, Vyas S, Hunot S.

Brain Proteins Pile Up in Parkinson’s Disease

•Alpha synuclein is an abundant brain protein• It plays an important role in the communication between nerve cells• In Parkinson’s Disease, it piles up, causing death of nerve cells, and eventually loss of function

Pesticides Accelerate the Pile Up

of Alpha SynucleinToxicol Sci. 2013 Jun;133(2):289-97

Specific pesticide-dependent increases in α-synuclein levels in human neuroblastoma (SH-SY5Y) and melanoma (SK-MEL-2) cell lines.Chorfa A1,and others

Studied the role of rotenone, paraquat, maneb and glyphosate

“Our data support the hypothesis that pesticides can trigger some molecular events involved in […] Parkinson's disease.”

Genetics of Parkinson’s Disease

Toxicology. 2013 May 10;307:17-23.

The interplay between environmental and genetic factors in Parkinson's disease susceptibility: the evidence for pesticides.Dardiotis E1, and others

Abstract

[…] genetic susceptibility either in metabolism, elimination and transport of pesticides or in the extent of mitochondrial dysfunction, oxidative stress and neuronal loss may predispose individuals to PD if they have been exposed to pesticides

These individuals will be dependent on their beneficial bacteria to detoxify.

Do pesticides affect our beneficial bacteria?

•Glyphosate interferes with the shikimate pathway, which does not exist in animals

•Good, since we are animals!! So is it safe?

•But our beneficial bacteria are not animals•What is the effect on our gut microbiome?

Glyphosate Could Alter Gut Microbes

Curr Microbiol. 2013 Apr;66(4):350-8.

The effect of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro.Shehata AA1, Schrödl W, Aldin AA, Hafez HM, Krüger M.

Abstract

[…] The presented results evidence that the highly pathogenic bacteria as Salmonella Entritidis, Salmonella Gallinarum, Salmonella Typhimurium, Clostridium perfringens and Clostridium botulinum are highly resistant to glyphosate.

However, most of beneficial bacteria as Enterococcus faecalis, Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis and Lactobacillus spp. were found to be moderate to highly susceptible.

Overgrowth of Clostridium botulinum

Anaerobe. 2013 Apr;20:74-8.

Glyphosate suppresses the antagonistic effect of Enterococcus spp. on Clostridium botulinum.Krüger M1, Shehata AA, Schrödl W, Rodloff A.

Abstract

“During the last 10-15 years, an increase of Clostridium botulinum associated diseases in cattle has been observed in Germany. The reason for this development is currently unknown.”

In humans: Clostridium difficile

• Pediatr Infect Dis J. 2013 Oct;32(10):1138-40.• Clostridium difficile infection in the hospitalized pediatric population: increasing trend in disease incidence.• Deshpande A1, Pant C, Anderson MP, Donskey CJ, Sferra TJ.

Understanding this system

•The more beneficial bacteria are impacted (pesticides, antibiotics, C-sections, etc...)

•The more efficient your genetics need to be to avoid harm from pesticides

•Over time, more and more people are being affected by chemicals

Conclusions

Pesticides affect • - gene expression • - beneficial bacteria• - inflammation in the central nervous system• - accumulation of important proteins (alpha synuclein)

There is a serious lack of information about the effect of combinations of chemicals

THE CHOICES

•Harmless

•Harmful and worth it

•Harmful and not worth it

Evaluating the Trade-offPROS• Cost• Time• Convenience • Esthetics• Force of habit

CONS- disruption of the immune system, resulting

in - any or all of the disease on the rise: autism,

ADHD, celiac disease, Crohn’s, ulcerative colitis, asthma, birth defects and childhood cancer, obesity and diabetes.