Pathophysiological Mechanisms of Gut Dysbiosis and Food Allergy and an Investigation of Probiotics as an Intervention for Atopic Disease.

Abstract

Background and aims: Epidemiological studies have associated reduced bacterial diversity and abundance and food allergy. This mechanistic review investigated the link between gut dysbiosis and food allergy with a focus on the role of short-chain fatty acids (SCFAs) in modulating T-cells. T-cell differentiation poses an opportunity to direct the immune cells towards an anergic regulatory T cell (Treg) or allergic T helper 2 (Th2) response. Probiotic intervention to prevent and/or treat atopic disease symptoms through this mechanistic pathway was explored.

Methodology: A narrative review was conducted following a three-stage systematic literature search of EMBASE and Medline databases. Ninety-six of 571 papers were accepted and critically appraised using ARRIVE and SIGN50 forms. Thematic analysis identified key pathophysiological mechanisms within the narrative of included papers.

Results: Preclinical studies provided compelling evidence for SCFAs' modulation of T-cell differentiation, which may act through G-protein coupled receptors 41, 43 and 109a and histone deacetylase inhibition. Foxp3 transcription factor was implicated in the upregulation of Tregs. Human probiotic intervention studies aimed at increasing SCFAs and Tregs and preventing atopic disease showed inconclusive results. However, evidence for probiotic intervention in children with cow's milk protein allergy (CMPA) was more promising and warrants further investigation.

Conclusion: Preclinical evidence suggests that the mechanism of gut dysbiosis and reduced SCFAs may skew T-cell differentiation towards a Th2 response, thus inducing allergy symptoms. Probiotic trials were inconclusive: probiotics were predominantly unsuccessful in the prevention of allergic disease, however, may be able to modulate food allergy symptoms in infants with CMPA.