AllergoOncology: Microbiota in allergy and cancer-A European Academy for Allergy and Clinical Immunology position paper

Abstract

The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti-ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune-related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for the development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome.

Keywords: allergy; cancer; hygiene hypothesis; microbiota; oncoimmunology.

Figure 1

Microbiota engineering. The three main approaches to microbiota engineering are depicted: left, interventions to modify the microbiota species composition; right, engineering biosynthetic pathways for the production of compounds benefiting human health and homeostasis; bottom, engineering selected commensal strains for therapeutic protein live delivery. At the center of each circled approach, a single bacterial cell is depicted as commensal representative. These approaches have possible overlaps that allow better tailored design. All approaches can be envisaged to ameliorate or even prevent both allergy and cancer

Figure 2

Interaction of microbiota with immune cells in health and disease. A, Bidirectional interaction between gut microbiome and players of the immune system. Cells from the epithelial barrier (epithelial cells and DC) sense the microbiome through the expression of a large panel of receptors. In health, such interactions are essential for the maintenance of the local microbial homeostasis and the integrity of epithelial barriers. This mechanism involves a variety of regulatory immune cells resident in the gut mucosa as well as molecules secreted by the epithelial layer. B, Human eosinophils were shown to secrete, among others, high amounts of neurotoxin following phagocytosis of the pathogenic bacteria Clostridium difficile that were limited following the engulfment of Bifidobacterium bifidum. C, In vitro interaction of human mast cells with Lactobacillus rhamnosus and SCFAs results in their modified functions and phenotypes with the implication of the KCa3.1 channel as well as Gpr41, 43, and 109a, respectively. D, The differentiation of human monocytes into moDC in the presence of SCFAs induces modified secretory capacities compared to controls. E, The efficacy of adoptive T‐cell therapy was proven to be associated with the microbiome. The success of adoptive T‐cell therapy correlates with a peripheral increase and a more abundant tumor infiltration of CD8α⁺ DC producing IL‐12.63 Mouse treatment with SCFA results in the recruitment of bone marrow‐derived DC with impaired capacity to induce Th2 responses in the lung.55 Probiotics administered by gavage reduce the severity of allergic airway inflammation and AD through the reduction of eosinophil infiltration into the lung and skin, respectively77, 78