Butyrate Produced by the Gut Microbiome Encourages Favorable Macrophage Polarization

The gut microbiome produces a broad range of necessary, beneficial metabolites, but the effects of only a few are well understood. Butyrate is one of the better studied of these metabolites, particularly in the context of cognitive function. Butyrate encourages BDNF expression, which in turn upregulates neurogenesis. Butyrate also upregulates expression of FGF21, which adjusts metabolism in ways that mimic some of the beneficial effects of calorie restriction. Unfortunately, shifts in the balance of populations in the gut microbiome take place with age, and butyrate production decreases as a result.

The innate immune cells called macrophages adopt packages of behaviors known as polarizations in response to circumstances. In today's open access paper, researchers note that butyrate adjusts the polarization of macrophage cells, from the pro-inflammatory M1 polarization to the anti-inflammatory, pro-regenerative M2 polarization. This is generally advantageous in the context of aged, inflamed tissue that tends towards fibrosis. Fibrosis is a malfunction of normal tissue maintenance that leads to scar-like deposition of collagen extracellular matrix, degrading tissue function. Organs such as the heart and kidney suffer fibrosis in later life, and there is presently little that can be done about that after the fact. A number of lines of work have shown that adjusting macrophage polarization towards M2, to dampen inflammation, can be beneficial in fibrotic tissues, however, and hence the interest here in the effects of butyrate on these cells.

Butyric Acid Ameliorates Myocardial Fibrosis by Regulating M1/M2 Polarization of Macrophages and Promoting Recovery of Mitochondrial Function

Myocardial fibrosis (MF) refers to various quantitative and qualitative changes in the myocardial interstitial collagen network. It is mainly manifested by the proliferation of myocardial fibroblasts, which secretes extracellular matrix proteins to replace damaged tissues. It is a common pathological manifestation in the end stage of many cardiovascular diseases and is the result of imbalance of collagen synthesis and metabolism. When MF occurs, it will damage the myocardial structure and promote arrhythmia and ischemia, thus affecting the evolution and outcome of heart disease.

Recent studies have shown that gut microbiota has a variety of effects on the host. Indeed, the functions of gut microbiota like an endocrine organ, producing bioactive metabolites that affect the physiological function of the host. There is growing awareness of the importance of the gut in many cardiovascular health and diseases, of which the role of the "gut-heart" axis is particularly important. Butyric acid is a short-chain fatty acid (SCFA) from the microbial community that involves in a series of cellular processes in a concentration-dependent manner. It is a multifunctional molecule produced by the fermentation of dietary fiber in the intestinal tract of mammals.

Macrophages are key cells in the immune inflammatory response. Activated macrophages are generally differentiated into M1 and M2 phenotypes. In addition to playing a role in host defense, macrophages also ensure tissue homeostasis and inhibit inflammatory responses. In order to perform these seemingly opposite functions, macrophages show high plasticity and adopt a spectrum of polarized states, where M1 macrophages and M2 macrophages are extreme. Both M1 macrophages and M2 macrophages are closely related to the inflammatory response, among which M1 macrophages are mainly involved in the pro-inflammatory response, and M2 macrophages are mainly involved in the anti-inflammatory response. Functionally, M2 macrophages inhibit M1-driven inflammation and promote tissue repair.

We hypothesized that M1-related mitochondrial oxidative phosphorylation inhibition is the factor that prevents M1 from repolarization to M2. Increasing the plasma concentration of butyric acid helps to protect the mitochondria, thereby repolarizing M2 from M1 to inhibit the progression of MF. To this end, we constructed a rat model of MF and fed rats with butyric acid. Our results suggested that butyric acid ameliorated MF by regulating M1/M2 polarization of macrophages and promoting recovery of mitochondrial function.


Opinions on Butyrate supplements?

Posted by: august33 at June 16th, 2022 10:14 PM

I wonder if there is in vitro techniques to test hundreds if not thousands of microbiota for the production of key beneficial metabolites.

Interesting that Swansons has GABA (Gamma-Aminobutyric Acid), but not straight up butyric acid.

Posted by: Thomas Schaefer at June 17th, 2022 9:11 AM
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