Food Intolerance - Pathogenesis

Pathogenesis

The term food allergy is widely misused for all adverse reactions to food. Food allergy (FA) is a food hypersensitivity occurring in susceptible individuals, which is mediated by a classical immune mechanism specific for the food itself. The best established mechanism in FA is due to the presence of IgE antibodies against the offending food. Food intolerance (FI) are all other adverse reactions to food. Subgroups of FI are enzymatic (e.g. lactose intolerance due to lactase deficiency), pharmacological (e.g. reactions against biogenic amines, histamine intolerance), and undefined food intolerance (e.g. against some food additives). As knowledge of mechanisms and causes of food intolerance improve, nomenclature will be updated. There is no worldwide scientific consensus on the pathogenesis of food intolerance.

Food intolerances can be caused by enzymatic defects in the digestive system, can also result from pharmacological effects of vasoactive amines present in foods (e.g. Histamine), among other metabolic, pharmacological and digestive abnormalities.

A frequent misconception among the general public is confusion between cow's milk allergy (CMA) and cow’s milk intolerance, which is usually intolerance to lactose. There are at least two, and possibly more, distinct pathologies. Hypersensitivity to milk is often broadly classified into immunoglobulin E (IgE)-mediated allergy and non-IgE-mediated intolerance. The immunopathological mechanisms of non-IgE-mediated intolerance in particular remain poorly understood, and this has hindered the development of simple and reliable diagnostics. Adults with non-IgE-mediated intolerance to milk tend to suffer ongoing reactions without the development of tolerance. The precise immunopathological mechanisms of non-IgE-mediated intolerance remain unclear. A number of mechanisms have been implicated, including type-1 T helper cell (Th1) mediated reactions, the formation of immune complexes leading to the activation of Complement, or T-cell/mast cell/neuron interactions inducing functional changes in smooth muscle action and intestinal motility. Food antigens contact the immune system throughout the intestinal tract via the gut associated lymphoid system (GALT), where interactions between antigen presenting cells and T cells direct the type of immune response mounted. Unresponsiveness of the immune system to dietary antigens is termed "oral tolerance" and is believed to involve the deletion or switching off of reactive antigen-specific T cells and the production of regulatory T cells (T reg) that quell inflammatory responses to benign antigens. In the case of IgE-mediated allergies, a deficiency in regulation and a polarisation of specific effector T cells towards type-2 T helper cells (Th2) lead to signalling of B-cells to produce milk protein-specific IgE. Whereas non-IgE-mediated reactions (intolerances) may be due to Th1 mediated inflammation. Dysfunctional T reg cell activity has been identified as a factor in both allergy/ intolerance mechanisms.