A Role for Folate in Microbiome-Linked Control of Autoimmunity

Abstract

The microbiome exerts considerable control over immune homeostasis and influences susceptibility to autoimmune and autoinflammatory disease (AD/AID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), psoriasis, and uveitis. In part, this is due to direct effects of the microbiome on gastrointestinal (GI) physiology and nutrient transport, but also to indirect effects on immunoregulatory controls, including induction and stabilization of T regulatory cells ( T reg ). Secreted bacterial metabolites such as short-chain fatty acids (SCFA) are under intense investigation as mediators of these effects. In contrast, folate (vitamin B9), an essential micronutrient, has attracted less attention, possibly because it exerts global physiological effects which are difficult to differentiate from specific effects on the immune system. Here, we review the role of folate in AD/AID with some emphasis on sight-threatening autoimmune uveitis. Since folate is required for the generation and maintenance of T reg , we propose that one mechanism for microbiome-based control of AD/AID is via folate-dependent induction of GI tract T reg , particularly colonic T reg , via anergic T cells ( T an ). Hence, folate supplementation has potential prophylactic and/or therapeutic benefit in AID/AD.

Increasing taxonomic and functional characterization of host-microbiome interactions by DIA-PASEF metaproteomics

“…Therefore, the functional insights offered here might point towards an endogenous mechanism, by which the gut ecosystem aims at ameliorating neuropathic pain. This is an exciting hypothesis that may open new therapeutical avenues harnessing folate supplementation as already implemented for diverse autoimmune diseases ( Mölzer et al, 2021 ). Folate was reported to stabilize and increases the abundance of T reg lymphocytes in the colon ( Mölzer et al, 2021 ).…”

Bioinformatics Analysis Identifies Potential PANoptosis Key Gene in Psoriasis with Single-cell validation and screening of related natural drug

“…We speculate that the PRG TCN1 is involved in the immune in ammatory process in the pathogenesis of psoriasis by regulating the expression of folate to affect the PANoptosis process in keratinocytes. Also, the results of clinical trial research con rm the e cacy and acceptability of calcium folinate for the treatment of psoriasis [45]- [47]. This opens the door for further research by indicating that folate-related receptors may be the molecular targets for psoriasis.…”

Expanding the Characterization of Microbial Ecosystems using DIA-PASEF Metaproteomics

“…Therefore, the functional insights offered here might indicate a mechanism by which the gut ecosystem aims at ameliorating neuropathic pain. This is an exciting hypothesis that may open new therapeutical avenues harnessing folate supplementation as implemented for diverse autoimmune diseases 41 .…”

“…Moreover, folate stabilises and increases the abundance of Treg lymphocytes in the colon 41 . Interestingly, T reg lymphocytes alleviate chronic neuropathic pain by inhibiting the Th1 response via CD4+ helper cells 42 .…”