Kids these days! It seems like every second child has asthma, eczema, nut allergy or some other allergic or autoimmune issue. It probably won’t surprise you to hear that scientists now refer to an “allergy epidemic” occurring in Western countries.
Evidence is piling up which suggests that this dramatic increase in allergies amongst children may be caused by the adoption of a Western diet and the loss of chronic infectious diseases. They believe that this has occurred because of reduced exposure to poop, animals, bugs, disgusting snotty siblings (less kids per household, now), and way too much cleanliness.
Yes, you heard it right. Apparently it’s better to be that mud covered street urchin than the modern, pristine, clean cut child whose parents helicopter around them, swooping in with anti-bacterial wipes every time they look the wrong way at the outdoors.
Alarmingly, however, recent research focusing on acute leukemia, the most common childhood cancer in developed countries accounting for one third of all children’s cancers, has further highlighted the importance of exposure to microbes and infection (bugs and diseases) in early life.
A recent review paper by noted leukemia researcher Mel Greaves, PhD, FMedSci, FRS, director of the Centre for Evolution and Cancer at the Institute of Cancer Research (UK), presents strong evidence that leukemia is caused through a ‘two- step process’ of genetic mutation and exposure to infection.
So infections cause leukemia? Yes and no. Dr Greaves:
“Paradoxically, we think the problem is not infection but a lack of infection early in life.”
It seems that infections in early life “prime” the immune system, so that later infections won’t trigger leukemia.
The paper, published May 21 in Nature Reviews Cancer, suggests that a lack of microbial exposure in early life could increase the risk of developing leukemia.
The review looked at the origins of acute lymphoblastic leukemia (ALL) and specifically B-cell precursor (BCP) ALL, which has been increasing in Europe by around 1% each year. This is part of a 13% increase in the incidence of childhood cancers world-wide, with acute leukemias primarily found in industrialised societies.
Dr Greaves states, “What we are reporting is what I hope is a resolution to a 100-year controversy on what causes childhood leukemia. What we think is the major cause are patterns of infection that are characteristic of developed societies.”
The new analysis draws on evidence from 30 years of research across the globe on the genetics, cell biology, immunology and epidemiology of childhood leukemia. Based on this evidence, the authors conclude that the cause of BCP ALL is multifactorial, involving both patterns of infection and inherited genetics, as well as other modulators of risk.
It is a “paradox of progress in developed societies” in which there is a mismatch between the evolutionary programming of the immune system and modern lifestyles that limit opportunities for microbial exposure early in life.
Greaves explains, “The development of leukemia develops in two discrete steps.”
The first step involves a genetic mutation that occurs before birth and predisposes the infant to developing leukemia.
The second step is triggered by infection, which plays a dual role. A lack of microbial exposure early in life results in immune system malfunction, and similar associations have been observed for Hodgkin’s Lymphoma in young adults and for childhood allergies and autoimmune disease.
Early microbial exposures are protective whereas later infections can trigger the critical secondary mutations if the initial “priming’ failed to occur.
“The immune system has evolved to fight infections, and natural infections in the first few weeks and months of life prime the immune system,” said Greaves. “In the absence of that priming early in life, by natural infections, later immune responses are abnormally regulated.”
Inherited genetics, chance and probably diet further affect the risk of developing ALL.
The risk is relatively low, about 1 in 2000, Greaves explains and he suggested ways in which that risk can probably be reduced.
Encouraging children to mix with other children and particularly older children would be good. Dr Mel Greaves.
Greaves suggests that, “One is not to be overzealous about hygiene and over worried about it. Encouraging children to mix with other children and particularly older children would be good, and protracted breastfeeding for 3 to 6 months would be beneficial.”
Manipulation of the natural microbiome is also being investigated for early life immune disorders. Oral administration of benign synbiotics (probiotics) can have profound and beneficial modulating effects on the developing immune system.
Greaves also emphasizes that this two-step model applies only to BCP ALL, the rarer pro-B ALL in infants, childhood acute myeloid leukemia and childhood lymphoma appear to have different aetiology and pathogenesis.
He states, “ALL is probably a preventable disease. So the challenge is how can you possibly do that? We think the way to do this is to give to infants in the first year of life some form of exposure to microbials that’s benign and safe, and I’m reasonably optimistic that in perhaps a 5 to 10 year time frame we’ll see this translated into some real benefit.”
Dr Gwen Nichols, chief medical officer at the leukemia & Lymphoma Society, commenting on the paper noted, “This may have implications well beyond childhood leukemia”.
“This paper provides good evidence that an interaction between genetics and the immune system play into the development of this disease. A lot of the pieces of the puzzle are starting to be understood about the interaction of the environment, genetics and the immune system.”
So, does all this mean you should take your newborn baby and rub her all over the dog? Or plop your 2 month old into a mud puddle? Or have your toddlers slobber all over the baby after going to the toilet without washing their hands? The jury is still out on these ones! It’s certainly becoming clearer that an overly sterile environment is not ideal and may well contributing significantly to all sorts of childhood problems.
References
Umetsu, D.T., McIntire, J.J., Akbari, O., Macaubas, C. & DeKruyff, R.H. Asthma: an epidemic of dysregulated immunity. Nat. Immunol. 3, 715–720 (2002).
Nature Rev Cancer May 21, 2018
Bach, J.F. The effect of infections on susceptibility to autoimmune and allergic diseases. N. Engl. J. Med. 347, 911–920 (2002).
Rook, G.A. Hygiene hypothesis and autoimmune diseases. Clin. Rev. Allergy Immunol. 42, 5–15 (2012).
Tun, H.M. et al. Exposure to household furry pets influences the gut microbiota of infant at 3-4 months following various birth scenarios. Microbiome 5, 40 (2017).
