25 Jan, 17 | by EBM
By Dr. Geoffrey Modest
Another microbiome article (I realize this is the third in a series of two, but can’t help myself). This one looked at the “hygiene hypothesis”, which is basically that kids exposed to more microbes early in life have fewer allergies or asthma. This article looked at thumb-sucking, nail-biting and atopic sensitization, also finding that the more the fingers went into the mouth, the fewer had atopic sensitization (see DOI: 10.1542/peds.2016-0443).
- The Dunedin Multidisciplinary Heath and Development Study, a population-based birth cohort study of 1037 people (52% male) born in Dunedin (the second largest city in the South Island of New Zealand with 120,000 inhabitants), with follow-up at ages 3,5,7,9,11,13,15,18,21,26,32, and 38
- At age 5,7,9,11 the parents were asked about the kid’s thumb-sucking and nail-biting, along with an estimate of frequency
- Skin-prick testing was done at age 13 on 724 of the 1031 kids (70%), including testing for house dust mites, grass, cat, dog, horse, aspergillus, penicillium, and a few others; a positive test was a wheal >2mm larger than the negative saline control
- Detailed respiratory reviews were done since age 9
- The researchers controlled for potential confounders of sex and parental history for asthma or hayfever; breastfeeding; exposure to cat or dog in childhood (a prior analysis of this cohort showed that this exposure led to lower risk of atopic sensitization); parental smoking history, household crowding (total number of kids divided by number of rooms), socioeconomic status
- Overall 31% of children were frequent thumb-suckers or nail-biters at age >1yo
- Nail-biting or thumb-sucking were each found in 20% of girls and 17% of boys
- Incidence of atopy:
- Atopic sensitization in 38% of girls/52% of boys age 13; 58% of girls/61% of boys at age 32
- Asthma in 10% of girls/16% of boys age 13; 18% of girls/18% of boys at age 32
- Hayfever in 28% of girls/32% of boys age 13; 42% of girls/37% of boys at age 32
- For atopic sensitization, as compared to those without thumb-sucking or nail-biting:
- At age 13:
- There was an adjusted 36% lower likelihood of atopic sensitization: OR 0.64 (0.45-0.90) for either thumb-sucking or nail-biting
- A 36% lower likelihood if only thumb-sucking, OR 0.64 (0.42-0.97)
- A 30% lower likelihood if only nail-biting, OR 0.70 (0.47-1.10), nonsignificant
- At age 32:
- There was a 38% adjusted lower likelihood of atopic sensitization: OR 0.62 (0.45-0.86) for either thumb-sucking or nail-biting
- A 31% lower likelihood if only thumb-sucking, OR 0.69 (0.47-1.00), borderline significant
- A 29% lower likelihood if only nail-biting, OR 0.71 (0.49-1.02), nonsignificant
- The only significant difference for specific allergens was for house dust mites in those aged 32, though all of the others had trends that were almost significant
- At age 13:
- For asthma or hayfever:
- None were significantly associated, at either ages 13 or 32
- A dose-response curve (doing both thumb-sucking and nail-biting vs either one of them) was only evident at age 13
- This study further supports the “hygiene hypothesis”, though it was notable that the dramatic difference in atopy was only in the objective measurement of sensitization (but, one might argue that these clinical manifestations of atopy are what really matters….). Why not with asthma or hayfever?
- Is it just that these were by report and therefore less “reliable” than the objective measure of atopic sensitization?
- Asthma, also, is more complicated, given that atopy is only part of the issue playing into it
- Or, my guess, is that they were looking at kids who were already too old (there were no data on thumb-sucking and nail-biting during the preschool years), that immune tolerance largely develops earlier in life, and other studies showing a relationship between “hygiene” and atopic conditions (e.g. hayfever or asthma) included much younger children (see blogs listed below)
- The study does support the results of a prior study finding that in kids using pacifiers, there seemed to be fewer allergies later in life when the mothers sucked the pacifiers to clean them
- The proposed mechanism here is that exposure to bacteria and other microorganisms early changes the gut microbiome (and, see blog below about the respiratory microbiome); and the microbiome can change the function of helper T cell (TH) subsets, increasing the helper T cell type 1 (TH-1, which produce interferon-g, IL-2, TNF-b and leads to cell-mediated immunity) and decreasing helper T cell type 2 (TH-2, which produces a slew of interleukins which lead to strong antibody responses), with these changes promoting the development of immune tolerance to allergen exposures.
- But overall this study does support the concept that early exposure to some microbes leads to more immune tolerance. And thumb-sucking or nail-biting certainly increases exposure to a diverse variety of microbes.
See http://blogs.bmj.com/ebm/2016/09/19/primary-care-corner-with-geoffrey-modest-md-microbiome-and-type-1-diabetes-etc/ which includes an article on the microbiome and type 1 diabetes, and two more on the “hygiene hypothesis”: one on the increased incidence of autoimmune disease in kids in those born in North Karelia Finland (more automated, advanced technologically) vs the Russian side (same gene pool but more natural environment/exposures); and the other being the recent NEJM article finding the same type of difference for asthma in the Hutterites (industrialized farming) vs the Amish (traditional farming)
See http://blogs.bmj.com/ebm/2015/11/09/primary-care-corner-with-geoffrey-modest-md-gi-microbiome-in-little-kids-and-development-of-asthma/ which is a Canadian longitudinal study finding that early infancy microbiome changes increase the risk of childhood asthma; or http://blogs.bmj.com/ebm/2014/08/13/primary-care-corner-with-geoffrey-modest-md-asthma-and-early-exposure-to-allergens/ which looks at 4 US cities and similarly finding that early allergen exposure leads to more asthma
There was a blog I sent out 8/27/2014 (which did not make it into the BMJ blogs) which looked at the lung microbiome, showing that diet leads to changes in the TH1 and TH2 cells in the lung itself (i.e., there is more than one microbiome, not just the gut one). For the article, see doi:10.1038/nm.3444. With regards to asthma: there is evidence of increased prevalence of chlamydia and mycoplasma with asthma exacerbations. Also, the respiratory microbiome is different in asthmatic vs nonasthmatic patients, even in asymptomatic asthmatic patients, with abundance of Proteobacteria. There is also some evidence that airway hyperresponsiveness tracks with bacterial diversity and composition (esp. increase in Proteobacteria).