Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases

Abstract

Gut microbiota has been well recognized in regulation of intestinal homeostasis and pathogenesis of inflammatory bowel diseases. However, the mechanisms involved are still not completely understood. Further, the components of the microbiota which are critically responsible for such effects are also largely unknown. Accumulating evidence suggests that, in addition to pathogen-associated molecular patterns (PAMP), nutrition and bacterial metabolites might greatly impact the immune response in the gut and beyond. Short-chain fatty acids (SCFA), which are metabolized by gut bacteria from otherwise indigestible fiber-rich diets, have been shown to ameliorate diseases in animal models of inflammatory bowel diseases (IBD) and allergic asthma. Although the exact mechanisms for the action of SCFA are still not completely clear, most notable among the SCFA targets is the mammalian G protein-coupled receptor pair of GPR41 and GPR43. In addition to the well-documented inhibition of histone deacetylases (HDAC) activity mainly by butyrate and propionate, which causes anti-inflammatory activities on IEC, macrophages, and dendritic cells, SCFA has recently been implicated in promoting development of Treg cells and possibly other T cells. In addition to animal models, the beneficial effects have also been reported from the clinical studies that used SCFA therapeutically in controlled trial settings in inflammatory disease, in that application of SCFA improved indices of IBD and therapeutic efficacy was demonstrated in acute radiation proctitis. In this review article, we will summarize recent progresses of SCFA in regulation of intestinal homeostasis as well as in pathogenesis of IBD.

Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches

“…These molecules include short-chain fatty acids (SCFAs), which stimulate mucosal protection and immune regulatory functions, bile acids, and injurious hydrogen sulfide. Levels of volatile organic metabolites are increased in stools and exhaled breath samples from patients with active IBD, whereas fecal levels of SCFAs are decreased 72, 127–129 . Decreased SCFA is consistent with lower concentrations of butyrate-producing commensal bacterial species, such as Lachnospiraceae, Roseburia, and F prausnitzii, 72, 96, 130 and the poor outcomes of persons with low dietary fiber intake 131 .…”

Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease

“…Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a group of chronic intestinal disorders of multifactorial etiology [1][2][3]. Although the precise pathogenesis of IBD remains poorly understood, dysregulated host-microbial interactions are considered to play a role in initiating and perpetuating IBD [1,3].…”

Progress and perspectives of short‐chain fatty acids in aquaculture

“…; Sun et al . ). Acetate, propionate and butyrate are rapidly absorbed from the gut lumen and perform their functions, including systemic autoimmune responses and participate in different steps of the inflammation process (Sun et al .…”

“…Acetate, propionate and butyrate are rapidly absorbed from the gut lumen and perform their functions, including systemic autoimmune responses and participate in different steps of the inflammation process (Sun et al . ). The potential roles of SCFAs in various cellular processes, including gene expression, differentiation, chemotaxis, proliferation and apoptosis, have recently been demonstrated (Corrêa‐Oliveira et al .…”