Butyrate Properties in Immune-Related Diseases: Friend or Foe?

Abstract

Butyrate is a short-chain fatty acid (SCFA) created within the intestinal lumen by bacterial fermentation of largely undigested dietary carbohydrates. Its beneficial effects on cellular energy metabolism and intestinal homeostasis have garnered significant attention among SCFAs. Butyrate also has systemic effects and is known to regulate the immune system. Most of the butyrate and other SCFAs are produced in the human colon, through the fermentation of dietary fiber or resistant starch. However, the modern diet often lacks sufficient intake of fermentable dietary fiber, which can lead to low butyrate levels in the colon. To increase butyrate levels, it is helpful to incorporate fiber sources into meals and drinks that rely on slow bacterial fermentation. Butyrate is well known for its anti-inflammatory properties and has a range of immune system-related properties. As an agonist for GPR41, GPR43, or GPR109A, butyrate may have anti-inflammatory effects through these receptors’ signaling pathways. Butyrate also serves as an epigenetic regulator, responding to environmental or pharmacological changes by inhibiting HDAC, up-regulating miR-7a-5p, and promoting histone butyrylation and autophagy processes. This review discusses the importance of butyrate in regulating immunological homeostasis and the inflammatory response. It also addresses experimental models and human studies investigating the therapeutic potential of butyrate supplementation in immune-related conditions linked to butyrate depletion. Specifically, it covers the role of butyrate in some immune-related diseases such as systemic lupus erythematosus, atopic dermatitis, psoriasis, human immunodeficiency virus, cancer, and several other special conditions.

A host-microbial metabolite interaction gut-on-a-chip model of the adult human intestine demonstrates beneficial effects upon inulin treatment of gut microbiome

“…With increased butyrate levels as a common denominator, the shared effects of the two exposure conditions are likely attributed to it. Indeed, butyrate is well known for its stimulating effects on intestinal epithelial barrier function and immune function and, therefore, can be considered a therapeutic intervention for IBD or other gastrointestinal diseases with a hampered barrier or immune activity [47,[86][87][88][89] . Several in vitro studies using Caco-2, HT-29, or other human-derived cell lines support the barrier-strengthening effect of butyrate [90][91][92] , but so far, this has not yet been confirmed in ex vivo human tissue.…”

Sodium butyrate alleviates R97-116 peptide-induced myasthenia gravis in mice by improving the gut microbiota and modulating immune response

“…Butyrate is an agonist for various GPCRs and stimulates anti-inflammatory cells including Tregs to reduce the activation of NF-κB and secretion of TNF-α to inhibit proinflammatory cytokines [ 58 ]. Activated T cells and cytokines play essential roles in the production of pathogenic autoantibodies and the induction of inflammation at the neuromuscular junction in MG [ 59 ].…”

Potential use of Sodium Butyrate (SB) as an anti-virulence agent againstVibrio choleraetargeting ToxT virulence protein

“…The hypothesis behind using SB as a therapeutic was that endogenously produced butyrate through fermentative process had a beneficial role in modulating the microbiota by providing energy to intestinal cells, having negative impact on harmful bacteria and regulating the immune related genes of the intestinal system (53–56). Our findings demonstrated similar repressive effect of this compound on the important virulence factors of V. cholerae .…”