Microbiome & Chronic Diseases

Evidence Based Medicine

Butyrate ⇒ Short Chain Fatty Acid {60000044}

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Meta Information

Structural Type:
Fatty acid
Functional Type:[  ]
Immun regulator, Anti-inflammatory, Anti-cancer


- Butyrate can act as an energy source for normal colon epithelial cells, promoting their proliferation, but can also inhibit proliferation and induce apoptosis. (1)

- Butyrate suppress proinflammatory factors, including IL-6, IL-12, and NO, from intestinal macrophages by HDAC inhibition.
- Butyrate restore bile acid dysregulation and counteract hepatic inflammation. (2)

- Mechanisms involved in gut microbiota-host communication. Short-chain fatty acids (SCFAs), mainly propionate, acetate, and butyrate, stimulate Fox3+ Tregs and macrophages via GPR43 activation and HDAC inhibition. Fox3+ Tregs subsequently produce the anti-inflammatory cytokine IL-10, while proinflammatory cytokines such as IL-6 and IL-12 are secreted by macrophages. Moreover, Th17 cells and effector memory T cells were downregulated by SCFAs. By suppressing PPARγ, SCFAs promote lipid oxidation. Although insulin production was enhanced by SCFAs, glycogenolysis and gluconeogenesis were both observed to occur even with SCFA treatment. L-carnitine and choline consumption contribute to the release of trimethylamine (TMA), which is then converted by FMO into trimethylamine N-oxide (TMAO). Both SCFAs and TMAO activate the NLRP3 inflammasome, leading to IL-18 and IL-1β release. Through the MAPK/NF-κB signalling pathway, TMAO increases the levels of COX2, IL-6, and ICAM1. Secondary bile acids such as deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are produced in the intestine by gut microbiota and then participate in inflammatory modulation and blood sugar regulation. (3)

- Butyrate suppresses proinflammatory genes and tumor growth, the latter via histone deacetylase inhibition, which downregulates oncogenic signaling pathways. (4)

Shared Notes

  • [1.9
    - Butyrate is the primary energy source of colonic epithelial cells, and adequate levels aid in maintaining barrier function.
    - Butyrate is essential in the maintenance of gastrointestinal health through inhibition of pro-inflammatory pathways and the reduction of oxidative stress within the colon.
  • [1.10
    - Butyrate is able to strongly inhibit the production of proinflammatory cytokines IL-12 and TNF-alpha by monocytes, whereas the anti-inflammatory cytokine IL-10 is significantly increased after bacterial stimulation.
    - Activation of Tregs by butyrate not only inhibits effector T cells but also produces the anti-inflammatory cytokine IL-10
  • [1.11
    - Butyrate, upregulate the Vitamin D Receptor signaling
  • [1.2
    - Dietary prebiotics, which can be metabolized by bacteria to produce butyrate, can be an intriguing new investigational approach to prevent immunotherapy-induced colitis and lead to improved patient outcomes.
    - Butyrate is a gut-microbiome-derived, anti-inflammatory metabolite that could be protective against ICI colitis, based on data from other forms of colitis.
    - Dietary prebiotic starches that can increase butyrate production are a promising method of microbial manipulation that could be used to mitigate ICI colitis.
  • - Butyrate are restricted to certain microorganisms belonging to the phylum Firmicutes or Akkermansia muciniphilla
  • [1.12
    - The TCA cycle is dysregulated in colonocytes, due to the lack of butyrate. However, upon supplementation of butyrate, isolated colonocytes from a germ-free mouse dramatically increased mitochondrial respiration.
  • [1.13
    - Butyrate-producing bacteria, like those belonging to Bacteroidetes and Firmicutes phylum, exert their anti-inflammatory activity metabolizing dietary fibers: A low-fiber diet leads to reduced production of butyrate, which acts as a negative regulator of pro-inflammatory pathways and enhances the intestinal barrier function.
    - When Fibre is scarce, intestinal bacteria use the intestinal mucus as a nutrient, which leads to inflammation through close contact between bacteria and the epithelial layer.
  • [1.3
    - The gut microbiota of moderate and severe Covid-19 patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial butyrate-producing bacteria such as Roseburia and Lachnospira genera.
  • [1.14
    - Colonization of the C. elegans gut with enteric bacterial pathogens disrupted proteostasis in the intestine, muscle, neurons, and the gonad.
    - The presence of bacteria that conditionally synthesize butyrate, a molecule previously shown to be beneficial in neurodegenerative disease models, suppressed aggregation and the associated proteotoxicity.
  • [1.15
    - MD-ketogenic diet improved the AD biomarkers viz. amyloid and tau proteins in the cerebrospinal fluids of MCI patients, wherein these changes linked with increased gut butyrate.
    - There is a significant reduction in Aβ levels and increase in behavioral responses after 12-weeks of sodium butyrate supplementation in mouse
  • [1.16
    - The SCFA receptor known as GPR109a is expressed on innate immune cells, adipocytes, and intestinal epithelial cells to respond to butyrate and niacin (vitamin B3), reducing inflammatory responses
  • - Butyrate was shown to rescue decreased GLP-1 receptor expression in the liver and decrease inflammation
  • [1.17
    - Increases in butyrate with increases in insulin and glucose, and decreases in HDL cholesterol and ghrelin.
  • [1.18
    - Ruminococcaceae (order Clostridiales) that are prominent producers of butyrate, decreased in relative abundance with a high-fat diet.
    - This decrease is particularly significant because Ruminococcaceae, making up ≈20% of gut bacteria in chow-fed OSA rats, decreased to ≈10% in high-fat OSA rats . Members of the order Clostridiales, other than Ruminococcaceae, also significantly decreased with high-fat diet.

Common References