The incidence of food allergies has increased dramatically in western countries over the past 20 years and the gut microbiota seems to be a promising target for preventing and treating them. However, mechanisms by which gut microbiota is involved in the loss of oral tolerance remain unclear.
A recent study, led by Dr. Charles Mackay from the Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology at Monash University in Clayton (Australia), has found that the development of food allergies in mice could be linked to dietary elements including fibre and vitamin A.
The researchers examined the beneficial roles of dietary fibre in peanut allergy using mice. Mice were fed on diets either depleted or enriched in fibre for at least 2 weeks. High-fibre feeding enhanced the activity of mucosal CD103+ dendritic cells (DCs), which are the main regulators of immune tolerance through promoting the differentiation of naïve T cells into regulatory T (Treg) cells in the mesenteric lymph nodes (MLN). The fibre achieved this effect by upregulating retinoic acid-synthesizing (RALDH) enzyme activity and enhancing antigen-specific Treg cell responses.
To study the effects of dietary fibre on oral tolerance in vivo, zero-fibre- and high-fibre-diet-fed mice were subjected to a model of oral tolerance involving multiple challenges with peanut extract. Antigen-challenged high-fibre-diet-fed mice contained a greater proportion of CD103+ DC and Treg cells in the MLN 3 days after tolerance induction. Besides this, total cell numbers in the MLN of high-fibre-fed mice were also significantly lower, which indicates a reduced inflammatory response.
Zero-fibre- and high-fibre-diet-fed mice had an induced food allergy in an experimental model of peanut allergy. Protection from food allergy under the high-fibre diet was associated with reduced clinical symptoms of anaphylaxis on day 28-which correlated with lower levels of serum immunoglobulin E (IgE)-and an increased proportion of both CD103+ DCs and Treg cells in the MLN (correlated with lower total cell numbers in the MLN). Other improved features observed in high-fibre-diet-fed mice were decreased production of T helper (Th)-2 cytokines IL-4, IL-5, and IL-13 from lymphocytes from the MLN and preserved gut epithelial permeability. High-fibre-mediated protection against food allergy relied on vitamin A metabolism and took place via promoting immunoglobulin A (IgA) and T follicular helper and mucosal germinal centre responses. Altogether, these results suggest that high-fibre feeding may enhance oral tolerance and protect mice against peanut allergy.
In order to study the role of gut microbiota composition in the protective role of high-fibre feeding in food allergy, germ-free mice inoculated with zero-fibre or high-fibre microbiota had a food allergy induced. Mice reconstituted with high-fibre microbiota had significantly better clinical anaphylaxis scores and a greater proportion of Treg cells compared to mice reconstituted with zero-fibre microbiota. Furthermore, the researchers investigated whether short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibres by the anaerobic intestinal microbiota, could mediate the beneficial effects of dietary fibre in the experimental model of food allergy. Mice were fed with acetate, butyrate, or propionate for 3 weeks prior to initial sensitization and throughout the experiment. Mice fed with acetate and butyrate showed a reduction in anaphylaxis clinical scores and total serum IgE levels, which correlated with the induction of CD103+ DCs and Treg cell responses and a lower total cell numbers in the MLN. However, SCFAs did not protect mice against food allergy in the absence of a gut microbiota. Besides SCFAs, another pathway by which gut microbiota can protect against food allergy involves commensal bacteria-induced MyD88 signalling. The authors also found that the beneficial effect of dietary fibre in mouse peanut allergy involved activity of SCFA receptors GPR43 and GPR109a, by influencing CD103+ DC responses and gut epithelial integrity.
To sum up, dietary fibre/SCFAs together with vitamin A and a healthy gut microbiota play key roles in protecting mice against peanut allergy. According to the researchers: “These findings support the notion that diets deficient in fibre, typical of many western countries, could underlie the rise of food allergies in recent decades”.
Tan J, McKenzie C, Vuillermin PJ, et al. Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways. Cell Rep. 2016; 15(12):2809-24. doi: 10.1016/j.celrep.2016.05.047.