The world is not germfree, and will never be

Axel Trautmann and Jörg Kleine-Tebbe in their allergy book are citing extensively Eugen Bleuler, Springer 1921 “Das autistisch-undisziplinierte Denken in der Medizin und seine Überwindung“:

Irrtümer, nicht Lücken, hindern die Wissenschaft am Fortschreiten. Zu den folgenschwersten Irrtümern gehört, daß man meint, etwas zu wissen, was man nicht weiß; und wenn man sich auch nur vor andern den Anschein gibt, etwas zu wissen, was in Wirklichkeit unbekannt ist, so hat das auf die andern und schließ lieh auf sich selber die nämliche Wirkung. [Outright errors not just some deficits set back science]

They probably know how allergy research has been driven by wrong assumptions.

Some people now even claim (according to press releases) that an allergy cure by altering the microbiome is being just around the corner. This is a bit like Otto Lilienthal, after some first drawings of a new wing speculating about an Airbus A380 to become the world’s largest passenger airliner.

Basically, these are even three recent Science papers, by Ohnmacht, by Arrieta and by Schuijs that mark current mainstream research. We know that children growing up on a farm may have somewhat less allergies (for whatever reason) but they are not protected from anything – it’s just an association.

Unfortunately these Science papers are also full of stereotypes and unjustified claim like “allergy reactions are on the rise” which isn’t true for the last decade (BRAUN-FAHRLÄNDER 2004, SELNES 2005 and ZÖLLNER 2005 showed a plateau) or “a direct effect of microbiota on type 2 cells such as T helper Th2 cells has not been documented” which is contradicted by reference 3 that already describes a CD4+T cell effect. Or some Myd88 disruption in B or T cells (HILL 2012), or some TLR4 effects (BASHIR 2004), or iNKT and CXCL16 accumulation (OLSZAK 2012), whatever you can think of.

I certainly do not have any problem to accept that early bacterial/ viral exposure is shaping the immune system, that’s what it is build for. There could be some Bacteroides fragilis or Clostridium induced changes, but none of all these Science papers tell you that germ-free often means also antigen-free. And any effect in antigen-free animals may be artifacts, as these animals have a lower cardiac output, higher permeable intestinal walls, increased basophils (HILL 2012), lymphocytic infiltration (HERBST 2011) and many more characteristics that are not IgE specific (HIRAYAMA 2007). My strongest objection, however, is that the Schuijs paper mixes observations in an isolated model system with a highly biased human observation. The mouse is a particular bad model system for human immunology (see 10 reasons) and A20 / TNFAIP3 gene variants have NOT been reported before in any asthma GWAS.

So will a germfree environment or even a reduced bacterial exposure make you allergic? AFAIK the first human to develop in a germ-free environment, David Vetter the “bubble boy” with SCID, didn’t have any raised IgE.

I tend to believe that these BL6 / Ova / SPF effects are an anomaly – as long as it is not shown to be reproducible in several other mice strains, under different rearing conditions and under allergen load. Sorry, but the C57BL strain is now imbred since 1921, there are numerous genetic polymorphism (Zurita 2011, Mekada 2015) with notable phenotypic differences (Herng-Yu Sucie Chang 2012) – again making para-effects likely.