The Microbiota-Bone-Allergy Interplay

Abstract

Emerging knowledge suggests an increasing importance of gut microbiota in health and disease. Allergy and bone metabolism are closely interconnected, and the possible negative effects of common therapies are not the only aspects of this relationship. The immune system is influenced by the microbiota-host interactions, and several pieces of evidence suggest the existence of an interplay between microbiota, bone metabolism, and allergies. Understanding these inter-relationships is essential for the development of new potential strategies of treatment and prevention targeting microbiota. A wide range of substances and germs, prebiotics and probiotics, are capable of influencing and modifying the microbiota. Prebiotics and probiotics have been shown in several studies to have different actions based on various factors such as sex, hormonal status, and age. In this review, we summarize the latest knowledge on the topic, and we discuss practical implications and the need for further studies.

Keywords: allergy; bone metabolism; food allergy; gut microbiota; inflammation; microbiota; osteoimmunology; osteoporosis; skeletal health.

Figure 1

The human gastrointestinal tract is colonized by about 10¹³–10¹⁴ microorganisms, of which 15,000 different bacterial strains are located mainly in the colon in a symbiotic relationship with the host. In normal conditions, the microbiota is characterized by the predominance of obligate anaerobic members of Firmicutes and Bacteriodetes phyla, which guarantee intestinal and general health, while the loss of homeostasis, dysbiosis, linked to the proliferation of some bacterial populations such as the Enterobacteriaceae or the absence of important commensal bacteria helps to create a more favorable environment for the growth of pathogens, predisposing the organism to pathological conditions.

Figure 2

SCFAs play a very important role in bone formation and mineralization by acting on the osteoprotegerin pathway, reducing osteoclastogenesis by suppressing the RANKL pathway, and reducing the pH of the intestinal tract by subsequently increasing the absorption of minerals.

Figure 3

SCFAs effects in immunological tolerance: induce gut dendritic cells (DC) to express retinal aldehyde dehydrogenase (RALDH), with result in the production of retinoic acid that upregulates expression of the gut-homing integrins α4β7 on peripheral regulatory T cells (Treg); promote immune tolerance, regulate the antibody response through the production of IgA and IgM; stimulate the production of anti-inflammatory mediators such as IFNγ and IL-10, which induce the expansion of Treg cells and the suppression of proinflammatory T helper 17 (Th17) and Th2 cells; reduce the production of proinflammatory cytokines including IL-1β, IL-6, and IL-17.