Oral tolerance

 

When we think about oral behaviors, such as oral sex or even something as seemingly trivial as picking and eating nose mucus, there’s an underlying biological mechanism at play that can have health implications—this mechanism is known as oral tolerance. While many parents may find habits like nail-biting, thumb-sucking, or eating mucus irritating, it’s worth considering the data before reacting too strongly. Research has shown that children who engage in at least one of these behaviors (nail-biting or thumb-sucking) during their preschool years have a 40% lower risk of allergic sensitization to common antigens as adults. 
 
 


 
Now, let’s break down how this works. When children explore their environment, touching objects and putting them in their mouths, they expose themselves to a variety of antigens—tiny particles collected under the nails or those present in the air, which get trapped in nasal mucus. This mucus acts as a filter, gathering information about potential environmental allergens.
 
Here’s the key: when a child consumes these particles, the immune system learns to recognize these antigens early on. This is critical because the gut is home to a significant number of immune cells that are constantly interacting with ingested antigens. By encountering antigens via the gut, the immune system develops a form of tolerance—this is the concept of oral tolerance. The gut processes these proteins in a way that teaches the immune system to accept them without triggering an allergic response. This is why ingesting antigens is preferable to exposure through the skin or respiratory tract, which can lead to allergic reactions.
 
Oral tolerance refers to the absence of a local or systemic immune response when antigens are introduced through the mouth, particularly in the case of food proteins. The local immune system in the gut processes these proteins and produces specific immune cells, known as Foxp3+ Tregs and Foxp3-Tregs, which contribute to both local and systemic tolerance, allowing for the safe consumption of food. The effectiveness of this process is age-dependent and influenced by the gut microbiome.
 
For a long time, the belief was that children should be shielded from highly allergenic foods. However, research shows the opposite is true. The earlier allergens like peanuts or eggs are introduced, the lower the risk of developing allergies. If these antigens enter the body for the first time through the skin or airways, they’re more likely to trigger allergic sensitization. For instance, exposure to peanut antigens on the skin can increase the likelihood of peanut allergies.
 
 The optimal window for introducing new foods is between 4 and 7 months of age. Removing antigens altogether doesn’t stimulate the development of tolerance.
So, what’s the takeaway? We shouldn’t be too quick to panic or scold children for these so-called "bad" habits. There’s some benefit to them. However, this immune education essentially ends by age five, so for adults, nail-biting and eating mucus are both unnecessary and, frankly, unpleasant. From an early age, it’s crucial to avoid an overly sterile diet, providing a variety of foods to help the immune system build tolerance and prevent allergies down the road.
 
Interestingly, oral tolerance mechanisms can also be relevant for adults. Scientific research suggests that oral sex (involving semen ingestion) can reduce the risk of preeclampsia and miscarriage. This is because the fetus is immunologically foreign, and semen contains high concentrations of male antigens. When these antigens are introduced into a woman’s body, they can stimulate the development of immune tolerance, reducing the risk of immune rejection of the fetus. Fascinatingly, the higher the concentration of specific HLA molecules (such as HLA-G) in semen, the lower the risk of preeclampsia. This is how oral tolerance plays a role in conception and pregnancy.
 
 
Annual Review of Cell and Developmental Biology Pediatric Allergic Diseases, Food Allergy, and Oral Tolerance Annu. Rev. Cell Dev. Biol. 2020. 36:511–28
Oral tolerance as antigen-specific immunotherapy Immunotherapy Advances, Volume 1, Issue 1, January 2021, ltab017,
Thumb-Sucking, Nail-Biting, and Atopic Sensitization, Asthma, and Hay Fever Pediatrics 2016 Aug;138(2):e20160443.
Oral sex is associated with reduced incidence of recurrent miscarriage Journal of Reproductive Immunology Volume 133, June 2019, Pages 1-6
Correlation between oral sex and a low incidence of preeclampsia: a role for soluble HLA in seminal fluid? Journal of Reproductive Immunology. 2000 Mar;46(2):155-66.