Gut bacteria play a role in whether our children will develop leukemia – and there may be a link with glyphosate and GM crops, writes Michelle Perro, MD

At-a-glance

  • Childhood leukemia is on the rise
  • Exposure to pesticides is known to increase the risk of childhood leukemia, as well as other types of cancer
  • New research links an impoverished gut microbiome (bacterial community) and chronic inflammation with increased risk of childhood leukemia
  • Diet-related ways are being sought to improve the microbiome and prevent the inflammation that triggers childhood leukemia
  • Glyphosate herbicides are used on around 90% of GM crops; glyphosate has been classified as a probable carcinogen by the World Health Organization’s cancer agency IARC
  • Exposure to glyphosate-based and other pesticides has been shown to disrupt the gut microbiome in laboratory animals
  • People who eat organic food have been found to have a 25% reduced risk of cancer
  • Clinical experience shows that switching to an organic and non-GMO diet improves people’s health
  • Controlled studies are needed to verify how switching to an organic and non-GMO diet affects the microbiome and certain disease conditions.

Cancers may take decades to develop, so they are often not seen until later in life. However, childhood cancers have risen globally by 13% over the past two decades, according to the International Agency for Research on Cancer (IARC), the World Health Organization’s cancer research agency.[1]

Childhood leukemia is still rare but nonetheless tops the list for the most common childhood cancer.[2] This form of cancer is treatable with a high success rate, but health issues stemming from the treatment can develop in subsequent years. There is a significant difference in success rates between countries, depending on medical access. However, treatment protocols are costly and require sophisticated children’s health centers to administer.

Previously, some viewed childhood leukemia as a random event or as genetically predetermined. While both these factors undoubtedly play a role, new research combined with clinical evidence suggests that there is much we can do to reduce the risk of this devastating illness affecting our children and their families.

Pesticides linked with cancer

There is clearcut evidence linking pesticide exposure to childhood leukemia.[3] [4] As early as 1999, an association was reported between domestic exposure to pesticides and childhood leukemia.[5] Pre-conception exposure of the father to pesticides and the fertilizers that are generally used with them was also found to be associated with an increased risk of this disease. Out of all the pesticides and other agrochemicals studied, fungicides and fertilizers were found to pose the highest risk.[6]

Certain commonly used pesticides have also been linked in epidemiological studies with other types of cancer. The widely used insecticide chlorpyrifos was found to be associated with an increased incidence of lung cancer in pesticide applicators.[7]

In 2015 the cancer agency IARC classified the herbicide active ingredient glyphosate as a probable carcinogen. The verdict was based on evidence from controlled lab animal studies and also from epidemiological studies on people exposed to glyphosate-based herbicides.[8] These are the most commonly used weedkillers worldwide and are used on around 90% of GM crops grown in the US.[9] In addition, glyphosate-based herbicides are applied as desiccants (drying agents) prior to harvest on various non-GMO crops, especially cereals such as oats and wheat, which is why high glyphosate residue levels are present in foodstuffs derived from these grains.[10] Furthermore, glyphosate-based herbicides are also used in gardens, parks, and public spaces. Therefore most of us are exposed to glyphosate, which explains why it repeatedly turns up in the urine of almost all US citizens who have been tested.[11]

Regulators reassure us that these residues are present at levels below safety limits and thus will not cause harm, but this is unconvincing since we now know that very low levels of certain chemicals can cause health impacts, especially involving hormonal systems, even when higher doses appear to be safe.[12] And a research study on pregnant women has correlated higher glyphosate levels in urine with shortened pregnancy length.[13]

The neglected food factor

Most epidemiological studies on pesticides and cancer focus on people exposed occupationally and through domestic or on-farm use of these chemicals. But there is a severe lack of studies on the health consequences of what for most people is likely to be the longest-term and main exposure route to pesticides: residues in food.

One remarkable exception is a 2018 landmark study in French adults, which found that people who consumed organic food most regularly – with its lower pesticide content – had a lower overall cancer risk, compared to people reporting little or no consumption of organic food. The organic food eaters had a 25% lower overall cancer risk – a reduction that, if it were credited to a new cancer drug, would make global headlines. In particular, significant differences in cancer rates were found for a cancer type called non-Hodgkin lymphoma (as much as an 86% reduction) and postmenopausal breast cancer, even after accounting for factors like socioeconomic status and exercise habits.[14]

The microbiome factor

Why would a low-pesticide-residue organic diet result in a reduced cancer risk? It’s likely that an important part of the answer lies in the gut microbiome, the community of friendly and not-so-friendly bacteria that live in our digestive tract. Research in recent years has clearly demonstrated the role of the gut microbiome in health and disease.

Starting in the first stages of life, the gut microbiome plays a key role in the development of the immune system. Newborns acquire their gut microbiome from various sites of their mother’s body, including the gut, mouth, skin, and birth canal.[15] The acquisition of this collective of microorganisms is responsible for setting up the baby’s innate immune system. Many factors can damage this relationship, including the modern focus on “anti-microbial” living, an impoverished gut microbiome in the mother, the effects of cesarean births, antibiotic use in the mother or baby, and an absence of breastfeeding.

In addition, there is evidence that exposure to pesticides can adversely affect people’s gut microbiome.

There has been interest within health-focused circles in the fact that Monsanto (now owned by Bayer) received a patent in 2010 for glyphosate as a parasite-control antibiotic.[16] But it is not known whether glyphosate-based herbicides, at the level to which humans are typically exposed, have an antibiotic effect on the gut microbiome. The effects of these herbicides on the human microbiome have not been studied.

Nevertheless, studies in rodents are considered to be relevant to human health – and such studies have found that the gut microbiome of these laboratory animals is sensitive to glyphosate-based herbicide exposure. Long-term exposure of rats to three different doses of Roundup (including one lower than the level permitted in drinking water in the EU) caused alterations in the gut microbiome.[17] Significantly, the alterations corresponded to those observed in non-alcoholic fatty liver disease, obesity, and systemic inflammation.[18] [19] In a separate study, medium- and long-term exposure of mice to Roundup altered the gut microbiome in terms of decreasing the abundance of certain bacteria. Roundup-treated mice showed an increase in anxiety and depression-related behavior, which was possibly caused by Roundup-induced gut dysbiosis (imbalance in the microbial community) and thus impaired gut-brain communication.[20]

A study conducted by Italy’s Ramazzini Institute exposed rats while developing in the uterus (from day 6 after conception) to either glyphosate or Roundup at the US regulatory permitted daily intake dose, and then orally after weaning until 28 days old. Microbiome profiling in fecal samples revealed alterations in the microbiome of both glyphosate- and Roundup-exposed rat pups especially before puberty. Longer-term studies are needed to see if these alterations lead to long-term disease.[21]

Other pesticides besides glyphosate also affect gut health and the microbiome. For example, chronic, low-dose exposure to the insecticide chlorpyrifos in a simulated human intestinal microbial ecosystem and in live rats was found to induce dysbiosis, with a proliferation of some strains and a decrease in others.[22] Chlorpyrifos is an organophosphate that is widely used for insect pest control on fruit and vegetable crops.

Certainly some components of the industrialized food system and lifestyle are affecting the microbiome, since children from more developed countries have less microbial diversity than children in less developed countries.[23] This alteration in the microbiome may cause disruptions in health. In my clinical practice, children with complex chronic diseases tend to show a lack of diversity as well as a low population number of microorganisms in their stools, as revealed in lab tests.

Leukemia-microbiome connection

Newly published research shows that environmental factors combine with genetics to increase the risk of childhood leukemia. Newly knighted scientist Dr. Mel Greaves, based at the Institute of Cancer Research in London, has been studying childhood leukemia for thirty years. He reports that acute lymphoblastic leukemia (ALL) is triggered by a genetic mutation occurring during fetal development. He says that for the immune system to develop properly, a child needs to be confronted with an infection in the first year of life: “Without that confrontation with an infection, the system is left unprimed and will not work properly.”

This is an increasing problem, he says, due to the over-use of antiseptic wipes, antibacterial soaps and disinfected floorwashes in the home. When the “unprimed” baby is eventually exposed to common infections, their immune system reacts abnormally and over-reacts with chronic inflammation and a release of chemicals called cytokines. These can trigger a second mutation, which results in leukemia in children carrying the first mutation. “The disease needs two hits to get going,” Dr. Greaves explained. “The second comes from the chronic inflammation set off by an unprimed immune system.”

In other words, a susceptible child suffers chronic inflammation that is linked to modern super-clean homes and this inflammation changes his or her susceptibility to leukemia so that they develop the full-blown condition.

As Dr. Greaves stated in his article in the journal Nature Reviews Cancer, “Microbial exposures earlier in life are protective but, in their absence, later infections trigger the critical secondary mutations. Risk [for ALL] is further modified by inherited genetics, chance and, probably, diet. Childhood ALL can be viewed as a paradoxical consequence of progress in modern societies, where behavioural changes have restrained early microbial exposure. This engenders an evolutionary mismatch between historical adaptations of the immune system and contemporary lifestyles. Childhood ALL may be a preventable cancer.”[24]

Dr. Greaves is looking at ways of blocking chronic inflammation in children in order to prevent leukemia from developing. He says, “We need to find ways of reconstituting their microbiomes … We also need to find which are the most important species of bacteria for priming a child’s immune system.”[25]

Dr. Greaves envisions creating a yogurt cocktail of microbes to restore children’s gut microbiome to a healthy state.

Bravo to Dr. Greaves for recognizing the role of the gut microbiome in the development of leukemia and the importance of diet in its prevention. However, what he doesn’t explore is that it may not be just the overuse of hand sanitizers and home cleaning products that are resulting in damage to the gut microbiome and causing chronic inflammation, but also the constant exposure to glyphosate (the active herbicide in Roundup) and other pesticides present in food.

In my clinical experience, the majority of patients with chronic disease have chronic inflammation as well. When they switch to an organic diet, which would reduce exposure to glyphosate and other pesticides, their gut microbiome status improves, chronic inflammation is reduced (as evidenced by decreased inflammatory markers) and immune function is enhanced, as evidenced by improvement in their health and laboratory tests.

In spite of all this, there is an evidence gap. We know that children eating an organic diet have lower levels of pesticides in their urine compared with children eating a non-organic diet.[26] But the relationship between urine pesticide levels and health status has not been proven in peer-reviewed controlled studies. Such studies are urgently needed to address this question.

What about GM foods?

As organic foods are not genetically modified, the question remains as to whether GM foods (associated pesticides apart) in themselves affect microbiome health and immune function. There are no studies looking at the effects of a GM food on the gut microbiome. However, a number of studies show that Bt insecticidal toxins (such as are expressed in GM Bt insecticidal crops) are immunogens[27] and allergens.[28] In other words, they can disrupt immune function.

One study showed that a GM Bt toxin produced in bacteria amplified the immune response of mice to other substances.[29] This suggests that GM Bt crops may trigger or worsen inappropriate immune responses to other substances.

It is crucial to good health to reduce chronic inflammation and build a strong immune system. But what comes first is the gut microbiome. Childhood leukemia is just one of a large number of ill health conditions – from obesity to anxiety to diabetes[30] – that are being linked to a disrupted gut microbiome. Sticking to a non-GMO and organic diet seems a commonsense way to maintain a healthy gut microbiome and reduce the risk of falling victim to chronic diseases.

Further research needed

New studies are urgently needed to look at how an organic and non-GMO diet could affect the gut microbiome, as compared with an equivalent diet of non-organic food that potentially contains GMOs. New research is constantly emerging showing that our gut microbiome has profound effects on our health, but much still remains to be learned. Further studies should investigate whether there is a correlation between common disease conditions and a particular gut microbiome profile.

As a health practitioner, altering the microbiome is part of my therapeutic strategy. I prescribe measures to strengthen the numbers and strains of beneficial bacteria, reducing known and potential pathogens, as well as to alter the ratios of various types of microbes found in the gut. As our gut bacteria derive their energy by breaking down indigestible fiber, a plant-rich wholefood diet is a good starting point.

However, controlled studies are needed to clarify and systematize treatment options that could be used by health practitioners globally. If consistent benefits are found from altering the gut microbiome via diet and supplementation, such research could inform public health policies and reduce the costs of chronic health problems to our healthcare system – as well as empowering people to improve their own health with a minimum of medical intervention.

References

  1. Steliarova-Foucher E et al (2017). International incidence of childhood cancer, 2001–10: A population-based registry study. The Lancet Oncology 18(6):719–731. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30186-9/fulltext?elsca1=tlpr
  2. American Cancer Society (2019). Cancers that develop in children. https://www.cancer.org/cancer/cancer-in-children/types-of-childhood-cancers.html
  3. Ward MH et al (2009). Residential exposure to polychlorinated biphenyls and organochlorine pesticides and risk of childhood leukemia. Environ Health Perspect 117(6):1007-13. https://www.ncbi.nlm.nih.gov/pubmed/19590698
  4. Hernández AFMenéndez P (2016). Linking pesticide exposure with pediatric leukemia: Potential underlying mechanisms. Int J Mol Sci. 17(4):461. https://www.ncbi.nlm.nih.gov/pubmed/27043530
  5. Infante-Rivard C et al (1999). Risk of childhood leukemia associated with exposure to pesticides and with gene polymorphisms. Epidemiology 10(5): 481-7. https://www.ncbi.nlm.nih.gov/pubmed/10468419
  6. Infante-Rivard C, Sinnett D (1999). Preconceptional paternal exposure to pesticides and increased risk of childhood leukaemia. The Lancet 354(9192):1819. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)70586-9/fulltext
  7. Josephson J (2005). Cancer: New chlorpyrifos link? Environ Health Perspect 113(3): A158. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1253789/
  8. IARC (2015). IARC Monographs Volume 112: Evaluation of five organophosphate insecticides and herbicides. Lyon, France; IARC. https://monographs.iarc.fr/iarc-monographs-on-the-evaluation-of-carcinogenic-risks-to-humans-4/
  9. USDA (2017). Recent trends in GE adoption. https://www.ers.usda.gov/data-products/adoption-of-genetically-engineered-crops-in-the-us/recent-trends-in-ge-adoption.aspx
  10. Food Democracy Now! and The Detox Project (2016). Glyphosate: Unsafe on any plate: Food testing results and scientific reasons for concern. bit.ly/glyphosateFood
  11. Niemann L et al (2014). A critical review of glyphosate findings in human urine samples and comparison with the exposure of operators and consumers. Journal für Verbraucherschutz und Lebensmittelsicherheit 10(1):3–12. DOI 10.1007/s00003-014-0927-3
  12. Vandenberg LN et al (2012). Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses. Endocr Rev 33(3):378–455. http://www.ncbi.nlm.nih.gov/pubmed/22419778
  13. Parvez S et al (2018). Glyphosate exposure in pregnancy and shortened gestational length: a prospective Indiana birth cohort study. Environmental Health 2018 17:23. https://doi.org/10.1186/s12940-018-0367-0
  14. Baudry J et al (2018). Association of frequency of organic food consumption with cancer risk: Findings from the NutriNet-Santé Prospective Cohort Study. JAMA Internal Medicine 178(12):1597-1606. doi:10.1001/jamainternmed.2018.4357.
  15. Ferretti P et al (2018). Mother-to-infant microbial transmission from different body sites shapes the developing infant gut microbiome. Cell Host & Microbe 24(1): 133-145.e5. https://www.sciencedirect.com/science/article/pii/S1931312818303172
  16. US Patent no. US7771736B2. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=/netahtml/PTO/search-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=7771736.PN.&OS=PN/7771736&RS=PN/7771736
  17. Lozano VL et al (2018). Sex-dependent impact of Roundup on the rat gut microbiome. Toxicology Reports 5:96-107. doi:https://doi.org/10.1016/j.toxrep.2017.12.005
  18. Serino M et al (2012). Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut 61(4):543-553. doi:10.1136/gutjnl-2011-301012
  19. Yan AW et al (2011). Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology 53(1):96-105. doi:10.1002/hep.24018
  20. Aitbali Y et al (2018). Glyphosate based herbicide exposure affects gut microbiota, anxiety and depression-like behaviors in mice. Neurotoxicol Teratol 67:44-49. doi:10.1016/j.ntt.2018.04.002
  21. Mao Q et al (2018). The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome. Environ Health 17(1):50. doi:10.1186/s12940-018-0394-x
  22. Joly C et al (2013). Impact of chronic exposure to low doses of chlorpyrifos on the intestinal microbiota in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) and in the rat. Environ Sci Pollut Res Int 20(5):2726-34. https://www.ncbi.nlm.nih.gov/pubmed/23135753
  23. De Filippo C et al (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA 107(33):14691–14696. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930426/
  24. Greaves M (2018). A causal mechanism for childhood acute lymphoblastic leukaemia. Nat Rev Cancer 18(8):471-484. https://www.ncbi.nlm.nih.gov/pubmed/29784935
  25. McKie R (2018). For 30 years I’ve been obsessed by why children get leukaemia. Now we have an answer. The Guardian, Dec 30. https://www.theguardian.com/science/2018/dec/30/children-leukaemia-mel-greaves-microbes-protection-against-disease
  26. Smith-Spangler C et al (2012). Are organic foods safer or healthier than conventional alternatives?: A systematic review. Ann Intern Med 157(5):348-66. https://www.ncbi.nlm.nih.gov/pubmed/22944875
  27. Vázquez-Padrón RI et al (2000). Characterization of the mucosal and systemic immune response induced by Cry1Ac protein from Bacillus thuringiensis HD 73 in mice. Braz J Med Biol Res 33:147–55. http://www.ncbi.nlm.nih.gov/pubmed/10657055
  28. Santos-Vigil KI et al (2018). Study of the allergenic potential of Bacillus thuringiensis Cry1Ac toxin following intra-gastric administration in a murine model of food-allergy. International Immunopharmacology 61:185-196. https://www.sciencedirect.com/science/article/pii/S1567576918302467
  29. Vázquez-Padrón RI et al (1999). Bacillus thuringiensis Cry1Ac protoxin is a potent systemic and mucosal adjuvant. Scand J Immunol 49:578–84. http://www.ncbi.nlm.nih.gov/pubmed/10354369
  30. Davis N (2018). The human microbiome: why our microbes could be key to our health. The Guardian. Mar 26. https://www.theguardian.com/news/2018/mar/26/the-human-microbiome-why-our-microbes-could-be-key-to-our-health