Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes

Abstract

Metagenomics studies have shown that type 2 diabetes (T2D) is associated with an altered gut microbiota. Whereas different microbiota patterns have been observed in independent human cohorts, reduction of butyrate-producing bacteria has consistently been found in individuals with T2D, as well as in those with prediabetes. Butyrate is produced in the large intestine by microbial fermentations, particularly of dietary fiber, and serves as primary fuel for colonocytes. It also acts as histone deacetylase inhibitor and ligand to G-protein coupled receptors, affecting cellular signaling in target cells, such as enteroendocrine cells. Therefore, butyrate has become an attractive drug target for T2D, and treatment strategies have been devised to increase its intestinal levels, for example by supplementation of butyrate-producing bacteria and dietary fiber, or through fecal microbiota transplant (FMT). In this review, we provide an overview of current literature indicating that these strategies have yielded encouraging results and short-term benefits in humans, but long-term improvements of glycemic control have not been reported so far. Further studies are required to find effective approaches to restore butyrate-producing bacteria and butyrate levels in the human gut, and to investigate their impact on glucose regulation in T2D.

Asiatic acid alleviates metabolism disorders in ob/ob mice: mechanistic insights

“…38 As for Eubacterium_xylanophilum_group, it has been shown to be able to produce butyrate, a short-chain fatty acid able to increase insulin sensitivity. 39,40 Another increased bacterium was Alloprevotella, and it has been reported that Alloprevotella is also a short-chain fatty-acid producer. 41,42 The liver breaks down toxic substances and prevents bacterial metabolites from entering circulation in the body.…”

Gestational Insulin Resistance Is Mediated by the Gut Microbiome–Indoleamine 2,3-Dioxygenase Axis

“…The GM serves as a crucial auxiliary in nutrition acquisition, maintaining gut homeostasis, and immune programming and playing an important role in host health and disease. 31 During pregnancy, the GM affects maternal and fetal health. 3,32 However, GM modulation of maternal adaptations to pregnancy is poorly understood.…”

“…Importantly, our data suggest that while the shift toward greater kynurenine levels may affect gestational glucose homeostasis, it may have contributions from a reduced AHR axis. Also, butyrate levels associate with and affect insulin sensitivity 31 and may activate the AHR pathway and transcription of AHR-dependent genes in intestine epithelial cells. 30 In our data, a decline in butyrate levels support a disturbed intestinal ecosystem at G15 and may represent another factor affecting pregnancy IR.…”

Orchestrating the fecal microbiota transplantation: Current technological advancements and potential biomedical application

“…(23). Recent research studies have shown that the Clostridia strains secreting butyrate were found in fewer numbers in the intestine of patients with type 2 diabetes mellitus, whereas non-butyrate-producing Clostridiales were found in a higher number of studies that showed that both insulin sensitivity and levels of butyrate-producing intestinal microbiota were markedly increased after microbiota transplantation (24). FMT has recently been shown to be helpful for regulating blood glucose and blood pressure in type 2 diabetic patients when supplemented with a particular diet over the course of a 3-month investigation.…”

“…( 23 ). Recent research studies have shown that the Clostridia strains secreting butyrate were found in fewer numbers in the intestine of patients with type 2 diabetes mellitus, whereas non-butyrate-producing Clostridiales were found in a higher number of studies that showed that both insulin sensitivity and levels of butyrate-producing intestinal microbiota were markedly increased after microbiota transplantation ( 24 ).…”