12 January - 20 June 2016

Mouse study finds a diet high in fibre can reduce severe peanut allergies

A mouse study published in Cell Reports has indicated that eating a diet high in fibre can actually shape the immune system to reduce allergies to substances such as peanuts.

A mouse study published in Cell Reports has indicated that eating a diet high in fibre can actually shape the immune system to reduce allergies to substances such as peanuts. 

Macia et al. report that food allergy develops following loss of oral tolerance.  However the exact mechanisms are unclear.  A number of explanations for increased incidence of food allergies have been proposed including diet and gut microbiome.

In the study, mice that were allergic to peanuts were fed either a high fibre diet (HF - 35% crude fibre) or a diet which lacked fibre or starch (ZF).  The HF mice compared to the ZF are reported to have had a similar amount of CD103 dendritic cells but a significantly higher proportion of CD103+ DC in the mesenteric lymph node. CD103 DC are present in large amount in the small intestine and migrate to the mesenteric lymph node to initiate oral intolerance.  CD103+ DCs are involved in the process of enhancing antigen-specific Treg cells (cells that suppress the immune response).   Macia et al. then examined whether this CD103+ DC effect could increase tolerance.  The scientists subjected the two groups of mice, HF and ZF, to multiple challenges with peanut extract. The antigen challenged mice had a greater proportion CD103+ DCs as well as an increase amount of Treg cells which express higher amounts of CCR9, suggesting that this was due to DCs themselves. Using a model of peanut allergy the scientists report that the HF diet reduced symptoms of anaphylaxis.  These mice also had lower levels of serum IgE (antibodies produced by the immune system) when compared to the ZF mice. 

Macia et al. report that RALDH2 which is an enzyme produced by CD103+ DC “converts vitamin A to retinoic acid, which promotes the differentiation of naive T cells into Treg cells.”  The team investigated whether tolerance from a HF diet depended on vitamin A metabolism.  A control group of mice were fed a standard diet for 12 weeks and then given a HF diet and a group of mice given a vitamin A deficient diet for 12 week (VAD) and then given a vitamin A deficient HF diet (VAD-HF).  Compared to the control, VAD diet and VAD-HF, the HF diet showed greater RALDH activity.  Mice fed on the VAD-HF, control and VAD diet showed significantly greater symptoms of anaphylaxis and total serum levels.  However although there were different amounts of CD103+ DCs between the HF and VAD-HFmice, both had greater number of Treg cells compared to the mice fed a control or VAD diet, which the authors indicate shows that “Treg cell induction by HF occurred independently of CD103+ cells.”

To confirm that changes in microbiota composition due to the HF diet bacteria could be responsible for the increase in IgA, bacteria from the guts of HF diet mice were given to a group of “germ-free” mice that had no gut microbe of their own.  The second group were then found to have increased levels of IgA despite not consuming a HF diet.  The authors also found that the second group of mice were protected against allergy showing a less severe response. The authors state that the microbiota was reshaped. 

The scientists state “the microbiota in the gut aided the immune system in resisting allergies by breaking down the fibre into short-chain fatty acids (SFA).  SFA’s have a strengthening effect on dendritic cells which go on to determine whether an allergic response is initiated.” They suggest that low levels of vitamin A and SFA’s could increase food allergies in infant and may explain why the highest incidence of allergies occurs in children and infants.

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