Adjust the intestinal environment with short-chain fatty acids

In a recent review published in the journal nutrients, Researchers review existing data on short-chain fatty acids (SCFAs), such as butyrate, acetate, and propionate, as important components of the human gut microbiome.

study: Short-chain fatty acid-producing bacteria: an important component of the human gut microbiota. Image credit: mi_viri / Shutterstock.com

prologue

The gut microbiota plays an important role in maintaining good health, including its barrier effect against pathogens, immune system maturation and function, regulation of dietary intake, and nutrient absorption. Gut microbiota abnormalities have been observed in several diseases, and numerous gut microbiota-based therapeutics are currently being investigated to manage chronic diseases. Clinically relevant pathways for modulating the gut microbiota include restoration of SCFA levels to improve cardiometabolic health.

In the current review, researchers presented an overview of associations between SCFA levels and human health.

SCFA in human health

SCFA transporters present on the epithelial surface of the colon, including monocarboxylic acid transporters-1 (MCT-1) and MCT-4, sodium-binding MCT-1 (SMCT-1), and breast cancer resistance protein (BCRP), are responsible for SCFA mediates the effect of to the intestine.

SCFAs increase the permeability and integrity of the intestinal barrier. For example, butyrate increases the concentration of tight junction proteins such as occludin, claudin-1 and zonaoccludence-1 by upregulating the genes encoding the respective proteins.

Butyric acid also increases mucin 2 (MUC-2) expression, regulates oxidative stress levels, reduces deoxyribonucleic acid (DNA) damage by hydrogen peroxide, reduces reactive oxygen species (ROS) production, and restores glutathione levels. , strengthens the intestinal epithelial mucus layer. SCFAs also induce cell differentiation and/or apoptosis to prevent cancer.

SCFAs can also modulate intestinal gluconeogenesis induced by the brain. In particular, propionate activates free fatty acid receptor-3 (FFAR-3), which is located in the outermost layer of afferent periportal neurons.

SCFAs have also been shown to inhibit histone deacetylase (HDAC) activity, which may in turn influence the pathophysiology of neuropsychiatric disorders such as Alzheimer’s disease, schizophrenia, and depression.

In addition, SCFAs modulate neuronal and systemic inflammation by regulating microglial cell structure and function, as well as emotional and cognitive functions. SCFAs may also affect brain barrier integrity by inducing tryptophan 5-hydroxylase 1 enzyme production, thereby increasing serotonin synthesis.

SCFAs such as acetate, through G protein-coupled receptors (GPR)-41 and GPR-41, modulate food intake and inhibit satiety hormones such as peptide YY (PYY) and glucagon-like peptide-1 (GLP-1). Decreases appetite by increasing levels. 43 activity and HDAC inhibition.

Propionate decreases hepatic gluconeogenesis, while butyrate and acetate increase leptin levels and decrease lipogenesis, body weight, and serum triglyceride levels. In addition to preventing thrombosis by reducing the expression of (PAI-1), it lowers blood pressure levels by binding to GPR-41 and causing vasodilation.

In addition, SCFA reduces myeloperoxidase (MPO) levels and decreases monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) levels, thereby promoting inflammatory cell chemotaxis. reduce the fading ability. SCFA also tightens regulations T cells (Treg) count and reduce intestinal inflammation by reducing nuclear factor kappa B (NF-κB) activity and associated cytokine release.

Relationship between SCFA production and human disease

especially intestinal bacteria Firmicutes species containing Lactobacillus, Ruminococcaceae, and Lachnospiraceae It produces SCFAs from complex polysaccharides by hydrolysis. In addition, actinomycetes, proteobacteriaand Fusobacteria Can produce butyric acid.

Acute inflammation protects the gut from harmful stimuli such as viruses and bacteria. If unresolved, these injuries can progress to chronic inflammation, which is associated with disorders such as inflammatory bowel disease (IBD).

Patients with IBD often have reduced abundance of butyrate-producing organisms, including: Rosebria and Faecalibacterium prausnitzii, thereby lowering SCFA production. Acetate controls tissue homeostasis through activation of the NLR family pyrin domain-containing 3 (NLRP-3). By comparison, butyrate modulates the intestinal barrier that is compromised in IBD through increased claudin-1, amphiregulin (AREG), and interleukin-22 (IL-22) levels.

Colorectal cancer increases the amount of pathogenic microorganisms, including: Fusobacterium nucleatum It has also been observed that the abundance of butyrate-producing bacteria is reduced, resulting in lower SCFA levels and increased inflammation.

Butyrate promotes tumor cell apoptosis by altering the redox state and D-glucose metabolic pathways. In hypertension, a decrease in the number of intestinal microbes that produce butyrate and poor intestinal absorption of SCFAs have been observed.

SCFAs, especially butyrate, regulate cardiac inflammation and stabilize plaque by reducing levels of matrix metalloproteinase-2 (MMP-2), VCAM-1, and chemokine ligand-2 (CCL-2). , thereby reducing macrophage migration and increasing collagen deposition.

Obesity is associated with intestinal dysbiosis. Firmicutes/bacteroides ratio. In addition, type 2 diabetes is associated with decreased numbers of butyrate-producing microbes and decreased circulating SCFA levels.

SCFAs improve glucose homeostasis through adenine monophosphate (AMP)-activated patient kinase (AMPK)-dependent and peroxisome proliferator-activated receptor gamma (PPARγ) regulatory effects. SCFAs also inhibit lipolysis and increase lipogenesis.

Conclusion

SCFAs are essential components of the gut microbiota that maintain cardiac metabolic health. Microbiota-dependent SCFA production can be enhanced by consuming a high-fiber diet such as a Mediterranean, vegan, or vegetarian diet. Prebiotics such as arabinoxylan oligosaccharides (AXOS), lactic acid bacteria plant, Lactobacillus paracaseiand Lactobacillus rhamnosus It can also promote health and well-being.