Tag Archives: hygiene

Vitamin D traces in later life

This is basically an update of my 2017 Allergy paper where I asked about sequelae of early vitamin D supplementation.

Two extensively examined hypotheses are the hygiene hypothesis (lack of protective bacterial exposure which leads to subsequent allergy) and the vitamin D hypothesis (early vitamin D supplementation sensitizes newborns against allergens) …  The interesting question is: Are these concepts exclusive? …  There is some preliminary evidence that – like many other environmental factors –vitamin D may modify the human microbiome.

Only yesterday a paper popped up during a presentation of Amelie Baud about the influence of social partners and the gut microbiome. This 2018 study  tested gut microbial composition from 16S rRNA sequencing during the first year of life and subsequent risk of asthma in 690 participants

1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 year … the microbial composition was not affected by maternal asthma status suggests that only susceptible children, exposed to inappropriate microbial stimulation during the first year of life, may express their inherited asthma risk …. The five most discriminating indicator OTUs for each cluster were identified for PAM cluster 1 as Enterobacteriaceae, Staphylococcus, Streptococcus, Bifidobacterium and Enterococcus, and for PAM cluster 2 as Faecalibacterium, Bacteroides(x3), and Anaerostipes … the risk of developing persistent asthma was increased (adjusted hazard ratio (aHR) 2.87 (1.25−6.55), P = 0.013) if the microbiome remained in PAM cluster 1 at age 1.

IMHO this doesn’t look very much like direct microbiome effects but some colliding  factor. The authors discuss cesarean section-birth and antibiotics as relevant factors while I wonder why the last author (who is a known pro vitamin D lobbyist ) doesn’t take into account vitamin D here?

My 2017 review summarized only early results, where there are now many more robust studies like the 2019 Naderpoor study

there was a significant association between community composition and vitamin D supplementation at the genus level. The vitamin D group had a higher abundance of genus Lachnospira, and lower abundance of genus Blautia (linear discriminate analysis >3.0). Moreover, individuals with 25(OH)D >75 nmol/L had a higher abundance of genus Coprococcus and lower abundance of genus Ruminococcus compared to those with 25(OH)D <50 nmol/L.

or the 2020 Singh paper

Vitamin D supplementation significantly increased gut microbial diversity. Specifically, the Bacteroidetes to Firmicutes ratio increased, along with the abundance of the health-promoting probiotic taxa Akkermansia and Bifidobacterium. Significant variations in the two-dominant genera, Bacteroides and Prevotella, indicated a variation in enterotypes following supplementation.

So is the microbiome just an indicator of vitamin D exposure in genetic susceptible children?

Can criticial thinking been teached?

Yes, it can.

Already in 2017 there was a Lancet paper with the super-long title “Effects of the Informed Health Choices primary school intervention on the ability of children in Uganda to assess the reliability of claims about treatment effects: a cluster-randomised controlled trial”. The paper is extensively discussed at vox.com

Andy Oxman is obsessed with the study of bullshit health claims and how to prevent them from spreading.
For decades, he’s been trying to find ways to get adults to think critically about the latest diet fads, vaccine rumors, or “miracle cures.” But he realized these efforts are often in vain: Adults can be stubborn old dogs — resistant to learning new things and changing their minds.

So not only Germany but also Uganda has its own bullshit hypothesis.

City-Country-River

In1989, we compared the City of Munich and Upper Bavaria in a big study. Although we did not find so many differences, there is an increased interest now in city – urban differences. Another two papers appeared yesterday, one in ScienceVulnerability of the industrialized microbiota” and one in Environment InternationalUrban-associated diseases: Candidate diseases, environmental risk factors, and a path forward“. The latter study finds
Continue reading City-Country-River

Claim to fame of the hygiene hypothesis

The recent encyclopedia article about the hygiene hypothesis seems to be well written. At least on the first instance … in reality it is more a novel than a scientific review.

For many years already, the hygiene hypothesis has been called an outdated concept; various times it was revised and transformed, and finally it gave birth to novel hypotheses.

In other words, the hypothesis has been rejected for being wrong . Even many revisions did not change that. There seem to be only one proven fact – the obsession of some authors with hygiene and nouvel Rousseauism.

Anyway, the hygiene hypothesis has promoted radical rethinking of infections, microbiota, and coevolution of mankind and microbes.

There is nothing radical in backward thinking. We still carry tons of microbes, freezer and antibiotics only did some qualitative but not so much quantitative changes,

With the advent of novel high-throughput sequencing technologies the human microbiome, which is sometimes called the ‘forgotten organ,’ has attracted much attention and is currently being implemented in a wider concept of self-foreign relationship, which may even include recognition of the nonmicrobial nonself as a vital stimulus to a well-developing immune system.

  1. So the interest is technology and not science driven.
  2. The microbiome is not an organ.
  3. The hype is already over.
  4. The Self is not defined by any bacterium.
  5. Most bacteria are excreted and not vital stimulus.

Given the many molecule classes regulating immune functions across individuals such as short RNAs, the hygiene hypothesis may eventually come back as a surprising explanation of the phenomena evoked by crowding, day care, sibship size, orofecally transmitted diseases, and respiratory infections.

Why that?
A comeback of the hygiene hypothesis by short RNA?
The listed phenomena are not intrinsically related, but are occuring only at the same time scale.

Even the old birth order effect might be rediscovered as epigenetic programming someday. Admittedly, these notions are entirely hypothetical, but without hypotheses, proven or not, science hardly advances.

So if David Strachan’s birth order effect would be really caused by  epigenetic programming – why would that be related to hygiene at all?

Science is is not so much about proven or unproven but about reasonable and non reasonable hypotheses.

 

Cure asthma: Pseudoscience?

I just came around of an EU funded research program “Cure, Eubiosus Reinstatement Therapy” that has many characteristics of quack science.

For a definition of quackery I suggest to look for Continue reading Cure asthma: Pseudoscience?

Window of Opportunity

I very much liked the “Window of Opportunity” in the Nestle Nutrition Workshop Series 61, published by Karger in 2008. Page 180 has an interesting account of the hygiene hypothesis:

Dr. Bier: … The other is the issue of the hygiene hypothesis, the cleaner environment. We are just in a somewhat less dirty environment, we are not in a clean environment, and that is the problem I have with that particular approach.

So, I am not alone

Dr. Barker:… I am guilty of inventing the term “hygiene hypothesis” as an explanation of the epidemic of appendicitis that followed the introduction of running hot water into housing of Western countries.

According to Sozanska et al. the hygiene hypothesis has more fathers

In 1970, Peter Preston1 posed the following question: ‘‘Is the atopic syndrome a consequence of good hygiene?’’ If this was the case, he argued that ‘‘the manifestations of atopy . would have appeared in given areas only after standards of hygiene . had been raised to high levels.‘‘

while David Strachan calls  it a misnomer since I know him. The last occasion was in the BMJ in August 2014

As the authors correctly point out, the term “hygiene hypothesis”, which is often attributed to my BMJ 1989 paper, is actually shorthand for a line of argument established much earlier. When presenting my own work, I regularly remind my audience that the ideas presented in the BMJ 1989 paper were inspired by David Barker’s publications on acute appendicitis a year or two before. However, as the authors acknowledge, Barker’s “hygiene hypothesis for appendicitis” was in turn influenced by earlier thinking.
I also recount that the inclusion of “hygiene” in the title of my paper (along with “hay fever” and “household size”) owed more to an alliterative tendency than to my aspiration to claim a new scientific paradigm. What interested me over the subsequent years was how, after initial disdain on grounds of implausibility, the immunological community enthusiastically endorsed the concept of the “hygiene hypothesis” as soon as they had proposed a cellular mechanism to explain it!
[…]
Indeed, the frustration over 25 years of epidemiological and immunological investigation is that so little progress has been made in identifying the biologically relevant exposures which “explain” the frequently replicated epidemiological observations linking allergic sensitisation and atopic disease (inversely) to family size and to “unhygienic” environments such as farming, separately and in combination…

Allergy, Vitamin D Receptor and Parabacteriodes

There was a congress abstract earlier this year by Rachid, Rima A et al. in  Journal of Allergy and Clinical Immunology:  “Food Allergy in Infancy Is Associated with Dysbiosis of the Intestinal Microbiota” where 137 infants (52 food-allergic and 85 controls) were enrolled and differences in fecal microbiota tested between the 2 groups. Food-allergic babies at 1-6 months of age had decreased abundances of genera in Bacteroidetes (Parabacteroides and Alistipes).

Interestingly, a new genome-wide association study of the gut microbiota using two cohorts from Northern Germany identified genome-wide significant associations for microbial variation and individual taxa at multiple genetic loci, including the VDR gene.  To further explore this association, they analyzed gut microbiota data fin Vdr−/− mice, confirming that loss of Vdr in mice substantially affects diversity. A more detailed exploration also showed that VDR consistently influences individual bacterial taxa such as Parabacteroides.

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So, is this a missing link?-Can vitamin D supplementation influence the gut microbial flora? This could explain even other observations. Right now rs7974353 is a rare human intronic SNP with no disease annotation.

Farm life does not prevent from asthma

In most farm children, asthma is not being prevented. And even in those children who might have had a benefit from being raised on a farm, it is not clear where the protection is mediated by: Some biological agent like endotoxin? Some healthy worker effect? Less medical interventions like antibiotics, Caesarean or vitamin D? It looks like other researchers are sceptical too

Others who study the hygiene hypothesis caution that the newly uncovered mechanism does not entirely explain the protective effect of dairy farm life. Drinking unprocessed milk also seems to ward off asthma in kids, points out Gary Huffnagle of the University of Michigan, Ann Arbor—and that effect is unlikely to involve the lung epithelium. What’s more, endotoxin levels are not that much higher on farms than in cities, suggesting “it’s too simple an answer,” says asthma genetics researcher William Cookson of Imperial College London, who thinks changes in living microbial communities in the lungs and gut may be just as important.

On verification

Most recently, I came across of another euphoric hygiene hypothesis review and wonder how this could ever happen. The evidence here is mixed and largely ambiguous.
Probably it would be best to follow some basic journalistic rules as summarized in the online “Verification Handbook for investigative reporting”

As with the verification of user-generated content in breaking news situations, some fundamentals of verification apply in an investigative context. Some of those fundamentals, which were detailed in the original Handbook, are:

– Develop human sources.
– Contact people, and talk to them.
! Be skeptical when something looks, sounds or seems too good to be true.
! Consult multiple, credible sources.
– Familiarize yourself with search and research methods, and new tools.
– Communicate and work together with other professionals — verification is a team sport.

Journalist Steve Buttry, who wrote the Verification Fundamentals chapter in the original Handbook, said that verification is a mix of three elements:

– A person’s resourcefulness, persistence, skepticism and skill
– Sources’ knowledge, reliability and honesty, and the number, variety and reliability of sources you can find and persuade to talk
– Documentation

Is this a retraction of the hygiene hypothesis?

There are news about the hygiene hypothesis.

Home cleanliness resulted only in quantitative reduction of floor dust, which mainly indicates removal of superficial dirt with a rather cosmetic effect. Conventional cleaning does not eradicate microorganisms sustainably, because emptied microbial niches are instantly recolonized by ventilation and living carrier.

Sure. Continue reading Is this a retraction of the hygiene hypothesis?

An epidemic of nonsense

13 € for a paperback, this is “An Epidemic of Absence. A new way of understanding allergies and autoimmune disease”. It is written by Moises Velasquez-Manoff , a journalist otherwise working for the “The Christian Science Monitor”. As his online bio reports “he dreamed of writing novels”. I would wish he would done so.

The outset is rather clear – Velasquez-Manoff wants to find a cure for his own autoimmmune disease. While this may be a legitimate justification for collecting information about a given topic, the method by Velasquez-Manoff is not. At a first glance, it looks like a serious book, well written, interesting facts presented in a coherent manner followed by numerous references. Maybe that made such an impression on the (numerous) positive reviewers. Maybe all the positive reviewers are experienced science journalists that judged by the overall impression plus some common sense plus some specific knowledge. But, Velasquez-Manoff did never hear the other side (on p.310, he even admits who has read and commented on sections of the manuscript: exclusively scientists in favor of the hygiene hypothesis). To recognize that you need to be a scientist – journalists would not notice that.

I compiled a long list the errors but feel now, that it would be too time consuming to write that down here. As far as it concerns me (p. 99) there was no grant to win in Munich as the study Velasquez-Manoff is talking about was a commissioned study. And sorry (p.100) I wrote the full grant application comparing East and West Germany children and did large part of the field study. Furthermore, I am not convinced (p.101) that the East West German differences ever supported the hygiene hypothesis, it is something different. And it was not in 2000 (p.102) that someone published on day care (p. 102), we wrote that already in 1999. Audiatur et altera pars, yea, yea.

Will the bacterial flora protect you from you allergies?

Here is another post as the field seems to progress so fast with a new study on enterotypes of the human gut microbiome from

22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific.

The 3 clusters are Bacteroides (enterotype 1), Prevotella (enterotype 2) and Ruminococcus (enterotype 3) – no idea if these are under selective pressure from the host (genes!), from enviroment (antibiotics!) or from microbial competitors. When we look, however, at another study published also last week at Science magazine, it seems that at least one cluster has it’s own trick to get the right of residence by synthesizing a symbiosis factor. Continue reading Will the bacterial flora protect you from you allergies?

Tolerogenic effects of vitamin D?

A new allergy study published last month

hypothesized that prenatal vitamin D supplementation could induce tolerogenic DC at birth. To evaluate this hypothesis in an epidemiological setting, we quantified the gene expression levels of ILT3 and ILT4 in cord blood (CB) samples of a population-based birth cohort of farm and reference children.

ILT3/IL4 as a marker of tolerogenic DCs may be justified by data published by Chang but not by newer data Continue reading Tolerogenic effects of vitamin D?

The dirty little secret

A new editorial talks about the dirty little secret of mouse immunology

the striking difference between human and murine sensitivity to LPS toxicity

where humans are 100,000–fold more likely to die of an intravenous dose of LPS. And of course to cite another review on mice and (not) men Continue reading The dirty little secret