IT IS A DEAL WITH BACTERIA
Butyric acid is the result of anaerobic fermentation in the colon. Members of the Firmicutes genus, a classification of bacteria, are well known for producing butyric acid. More specifically, microbes like Roseburia spp., Faecalibacterium prausnitzii, and Eubacterium rectale are responsible to produce butyric acid mainly from undigested dietary carbohydrates, specifically resistant starches and dietary fiber, but also in a minor part by dietary and endogenous proteins. SCFAs are 2-carbon to 5-carbon weak acids, including acetate (C2), propionate (C3), butyric acid(C4), and valerate (C5). SCFAs are essentially produced in the colon. The ratio of SCFA concentrations in the colonic lumen is about 60% acetate, 25% propionate, and 15% butyric acid.
Effects on non-specific intestinal defense mechanisms
Reduction of colon pH As a result of increasing concentrations of SCFAs, the luminal pH in the proximal colon is lower. This pH seems to boost the formation of butyric acid, as mildly acidic pH values allow butyric acid-producing bacteria to compete against Gram-negative carbohydrate-utilizing bacteria, such as Bacteroides spp
Decrease gut permeability The main components of non specific intestinal barrier defense mechanisms are the mucous layer covering the epithelium, the production of antimicrobial peptides, and tight junctions, which protect the gastrointestinal mucosa against pathogens. Evidence suggests a role for butyric acid in reinforcing the colonic defense barrier. Butyric acid stimulates MUC2 mucin production in colonocytes. The increased expression of MUC2 gene, and the induction of mucin synthesis, can affect the mucous layer leading to enhanced protection against luminal agents.
Butyric acid promotes cathelicidins Combined with other components of the innate immune system, antimicrobial peptides (AMPs) form the first line of defense against infections. The two major classes of AMPs found in humans are defensins and cathelicidins. Several studies demonstrated an effect of butyric acid on cathelicidin gene expression. The use of butyric acid, to enhance the expression of the cathelicidin gene may become a novel approach for strengthening innate immunity to treat or prevent intestinal infections.
Butyric acid on epithelial oxygenation
The gastrointestinal tract is characterized by a particularly unique oxygenation profile. Its epithelium is trapped between the arteries that are rich in oxygen and the intestinal lumen that is an anaerobic environment. It is critical to maintain this gradient to be sure that the colonocytes are fed in oxygen from the arterial blood for its own ‘respiration’. The intestinal lumen must at the opposite remains with a very low level of oxygen as most of beneficial bacteria are anaerobic and would be killed by an increase of oxygen.
Research shows that butyric acid play a major role in maintaining this gradient of oxygen as it has a direct bearing on epithelial oxygen consumption. Intestinal epithelial cell lines stimulated with butyric acid exhibit an increased and sustained oxygen consumption rate that results in depletion of environmental oxygen relative to the epithelial fed with glucose. The depletion of the gut microbiota by the use of antibiotics was shown to increase the oxygen level in the colonic epithelium, as indicated by an oxygen-sensitive probe. Restoration of the luminal butyric acid in antibiotic- treated mice reconstituted the physiologic low level of oxygen of the colonic epithelium. Interestingly, Donohoe et al. showed that, compared with conventionalized mice, the colonocytes of germ-free mice are ATP-deficient and the provision of butyric acid can reverse this energy deficit by restoring oxidative respiration.
Very recently, Rivera-Chavez et al. (2016) reported that streptomycin treatment depleted commensal, butyric acid-producing bacteria from the mouse intestinal lumen, leading to decreased butyric acid levels, increased epithelial oxygenation, and aerobic expansion of Salmonella enterica serovar Typhimurium. Epithelial hypoxia and Salmonella restriction could be restored by the addition of synthetic butyric acid in the diet.
Thus, given the voracious consumption of the epithelium in oxygen in the presence of butyric acid, it is possible that the presence of butyric acid in the colon could, at least in part, explain the low level of oxygen in this lumen.
Effects on trans-epithelial water and ions transport
The absorption of butyric acid has been shown to promote the absorption of sodium, potassium, and water, the effects that give it antidiarrheal properties. Butyric acid is able to exert a powerful pro-absorptive stimulus on intestinal NaCl transport and an anti-secretory effect towards Cl- secretion. Butyric acid can be coupled to Na+ and Cl- and go through the membrane together. Water, as always, is absorbed in response to an osmotic gradient.The more Na+ is absorbed and the more water will follow.
Dysbiosis, a primary cause of diarrhea, is caused by an antibiotic disturbance of the gut microbiota that suppresses their fermentation and production of butyric acid. Several studies demonstrated that, in situation of dysbiosis, the addition of synthetic butyric acid in the diet enable animals to limit diarrhea and contribute to bring back eubiosis.
Effects on inflammatory and oxidative status
Butyric acid has a role as an anti-inflammatory agent, primarily via indirect inhibition of interleukine (1b, 2, 6, 8 and 12) and cyclooxygenase-2 (COX-2). Moreover, butyric acid can act on immune cells through specific G-protein-coupled receptors (GPRs) which are both expressed on immune cells suggesting that butyric acid might be involved in the activation of leucocytes.
Numerous studies have reported that butyric acid metabolism is impaired in intestinal inflamed mucosa. Recent data show that butyric acid deficiency results from the reduction of butyric acid uptake by the inflamed mucosa through down regulation of MCT1. The concomitant induction of the glucose transporter GLUT1 suggests that inflammation could induce a metabolic switch from butyric acid to glucose oxidation. Butyric acid transport deficiency is expected to have clinical consequences.
Evidence from pre-clinical studies shows that oxidative stress in the colonic mucosa can be modulated by butyric acid. During oxidative stress, there is an imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defense mechanisms, leading to a cascade of reactions in which lipids, proteins, and/or DNA may get damaged. In healthy humans, it has been demonstrated that locally administered butyric acid in physiological concentrations increased the antioxidant GSH and possibly decreased ROS production, as indicated by a decreased uric acid production. As the animal colon is continuously exposed to a variety of toxic stimuli, enhanced butyric acid production in the colon could result in an enhanced resistance against toxic stimuli, thus improving the barrier function.
Given the importance of butyric acid in the gut physiology, most nutritionist are studying the addition of synthetic butyric acid. One of the major problems in the application of butyric acid is the difficulty in handling it. Butyric acid has an offensive odor making it unpleasant to work with, and can deter animals from consuming feed with free butyric acid incorporated. Moreover, free butyric acid has been shown to be largely absorbed in the upper GIT, meaning that the majority would not reach the large intestine, including the colon, where butyric acid would exert its major functions. Bacterial butyric acid is directly produced in the colon where it will be utilized. But synthetic butyric acid needs to travel from the mouth to the colon without being destroyed or absorbed. We must therefore select the proper form of butyric acid to ensure a proper delivery and utilization.
The conclusion of that nutricle is that host and bacteria are not always competing. They could as well help each other. In the case of eubiosis in the gut, it is a three-way relationship. Butyric acid fuels colonocytes, and in return these cells help provide an oxygen-free environment in which beneficial gut microbes thrive. This keeps inflammation in check, gut cells healthy, and gut bacteria happy.
Comments