Fun! Wonderful find.
Ive never been able to get behind paleo as a lifestyle diet because of beans. I eat them every day and am better for it. I also continue to supplement butyrate.
Lately, Ive been very focused on the proteins that allow movement across membranes, which is another thing this video highlighted as well as epigenetic poly morphisms. It said a special protein on the cell allowed it to uptake the butyrate. The Solute Carrier Family is responsible for this. The solute Carrier family is the delivery system of the body, it knows all the passwords to all the secret doors. The SLC is the keymaker of our system's matrix.
www.guidetopharmacology.org/GRAC/ReceptorFamiliesForward?type=TRANSPORTERwww.ojrd.com/content/8/1/194 www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0020216Here is a bit about
how SLC5A8 is involved in butyrate transport. It also highlights other genes like GLUT1 and MCT1
MCT1/SLC16a1 is IMPORTANT for UCers -
www.ncbi.nlm.nih.gov/pubmed/21987487 Ive snippeted some parts out:
www.ncbi.nlm.nih.gov/pmc/articles/PMC3070119/Similar mechanisms could occur in CLD. Lastly, Clausen et al[20] demonstrated that antibiotic-associated diarrhea was related to reduced fecal concentrations and production rates of butyrate. Their results suggest that the antibiotic-associated diarrhea might be secondary to impaired colonic fermentation in otherwise disposed subjects, resulting in decreased butyrate and fluid absorption.
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EFFECTS OF BUTYRATE AT THE INTESTINAL LEVEL
Effects on transepithelial ion transport
Potentially, SCFAs are absorbed by each intestinal segment, as demonstrated in animal models and human volunteers. The colonocytes absorb butyrate and other SCFAs through different mechanisms of apical membrane SCFA uptake, including non-ionic diffusion, SCFA/HCO3- exchange, and active transport by SCFA transporters. The transport proteins involved are monocarboxylate transporter isoform 1 (MCT1), which is coupled to a transmembrane H+-gradient, and SLC5A8, which is Na+-coupled co-transporter. The absorption of these fatty acids has a significant impact on the absorption of NaCl and on the electrolyte balance generally. In particular, butyrate is able to exert a powerful pro-absorptive stimulus on intestinal NaCl transport and an anti-secretory effect towards Cl- secretion. The powerful regulatory pro-absorptive/anti-secretory effects induced by butyrate on the transepithelial ion transport occurs through several mechanisms: (1) Stimulation of NaCl absorption by the action of two coupled transport systems on the intestinal brush border: Cl-/HCO3- and Na+/H+ and Cl-/butyrate and Na+/H+; and (2) inhibition of Cl- secretion by blocking the activity of the cotransporter Na-K-2Cl (NKCC1) on the enterocyte basolateral membrane. In vitro studies have shown that butyrate has an inhibitory effect on Cl- secretion induced by prostaglandin E2, cholera toxin, and phosphocholine. This effect is due to reduced production of intracellular cAMP secondary to the expression and regulation of adenylate cyclase. Comparison studies showed that the pro-absorptive and anti-secretory effects of butyrate are significantly higher than those of all other SCFAs. Clinical studies in children with acute diarrhea caused by V. cholerae showed a reduction in stool volume and a more rapid recovery in patients who received oral rehydration therapy in addition to resistant starch, a precursor of butyrate, in the diet[7,8]. These results were confirmed in other forms of infectious diarrhea in children and in animal models studies[9,10]. Moreover, butyrate therapy is beneficial in patients affected by Congenital Chloride Diarrhea (CLD)[11,12]. This rare genetic disease is caused by mutations in the gene encoding the solute-linked carrier family 26-member A3 (SLC26A3) protein, which acts as a plasma membrane anion exchanger for Cl- and HCO3[13]. The mechanism underlying this therapeutic effect could be related, at least in part, to stimulation of the Cl-/butyrate exchanger activity[11]. It is also possible that butyrate could reduce mistrafficking or misfolding of the SLC26A3 protein, as demonstrated for other molecules involved in transepithelial ion transport[14]. Alternatively, butyrate may enhance gene expression: the SLC26A3 gene contains a 290-bp region between residues -398 and -688 that is crucial for high-level transcript
ional activation induced by butyrate. This may explain the variable response of patients affected by CLD to butyrate[12]. In fact, depending on the patient’s genotype, mutations in the above-mentioned regulatory regions of the SLC26A3 gene could affect the gene transcript
ion rate. It is also conceivable that other channels could be involved in the therapeutic effect of butyrate in CLD. SLC26A3, like other components of the SLC26 family, interacts with cystic fibrosis transmembrane conductance regulator (CFTR)[15,16]. The interaction between CFTR and these components is mediated by binding of the regulatory domain of CFTR to the sulfate transporter and anti sigma factor antagonist (STAS) domain of SLC26. The interaction is enhanced by phosphorylation of the regulatory domain by protein kinase A[17] and is modulated by PDZ-binding scaffold proteins. An important consequence of this interaction is that SLC26 anion exchange activity is enhanced when CFTR is activated by phosphorylation. Moreover, the two genes regulate each other: the overexpression of SLC26A3 or -A6 causes upregulation of CFTR and vice versa. In patch-clamp experiments, protein kinase A-stimulated CFTR channel activity was six-fold higher in HEK293 cells co-expressing both SCL26 exchanger and CFTR than in HEK293 cells expressing CFTR alone. Mutations may impair the interactions between channels and thus reduce the effect of butyrate therapy. Interestingly, it has been demonstrated that butyrate can act by different mechanisms in in vitro models of cystic fibrosis: it can increase the expression of the apical epithelial membrane of the CFTR, and it can act as a “chaperone-like” molecule, as shown in the ΔF508del CFTR cell line model[19]. Similar mechanisms could occur in CLD. Lastly, Clausen et al demonstrated that antibiotic-associated diarrhea was related to reduced fecal concentrations and production rates of butyrate. Their results suggest that the antibiotic-associated diarrhea might be secondary to impaired colonic fermentation in otherwise disposed subjects, resulting in decreased butyrate and fluid absorption. In this case, the administration of butyrate could also alleviate the symptoms associated with antibiotic use.
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Most clinical studies analyzing the effects of butyrate on inflammatory status focused on UC patients. Hallert et al[60] instructed 22 patients with quiescent UC to add 60 g oat bran (corresponding to 20 g dietary fiber) to their daily diet. Four weeks of this treatment resulted in a significant increase of fecal butyrate concentration and in a significant improvement of abdominal symptoms. In a double blind, placebo-controlled multicenter trial, Vernia et al[61] treated 51 patients with active distal UC with rectal enemas containing either 5-aminosalicylic acid (5-ASA) or 5-ASA plus sodium butyrate (80 mmol/L, twice a day). The combined treatment with topical 5-ASA plus sodium butyrate significantly improved the disease activity score more than 5-ASA alone. These and other intervention studies[62-64] suggested that the luminal administration of butyrate or stimulation of luminal butyrate production by the ingestion of dietary fiber results in an amelioration of the inflammation and symptoms in UC patients.
Numerous studies have reported that butyrate metabolism is impaired in intestinal inflamed mucosa of patients with IBD. Recent data show that butyrate deficiency results from the reduction of butyrate uptake by the inflamed mucosa through downregulation of MCT1. The concomitant induction of the glucose transporter GLUT1 suggests that inflammation could induce a metabolic switch from butyrate to glucose oxidation. Butyrate transport deficiency is expected to have clinical consequences. Particularly, the reduction of the intracellular availability of butyrate in colonocytes may decrease its protective effects toward cancer in IBD patients[65].
Limited evidence from pre-clinical studies shows that oxidative stress in the colonic mucosa can be modulated by butyrate. Oxidative stress is involved in both inflammation[66] and the process of initiation and progression of carcinogenesis[67]. 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 butyrate in physiological concentrations increased the antioxidant GSH and possibly decreased ROS production, as indicated by a decreased uric acid production[68]. As the human colon is continuously exposed to a variety of toxic stimuli, enhanced butyrate production in the colon could result in an enhanced resistance against toxic stimuli, thus improving the barrier function. This might be relevant for the treatment of gastrointestinal disorders, such as post-infectious irritable bowel syndrome (IBS), microscopic colitis, IBD, and diversion colitis.
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So you ask yourself, why arent we using Butyrate?
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ISSUES RELATED TO THE CLINICAL USE OF BUTYRATE
Data from literature and clinical experience of several research groups show a wide spectrum of possibilities for potential therapeutic use of butyrate by oral administration without having serious adverse events (Table (Table2).2). Some butyrate-based products are marketed, but their spread is still very limited and greatly understaffed in view of the wide spectrum of possible indications, especially in chronic diseases, where it is possible to predict a lasting use of the compound. The main problem is of the availability of formulations of butyrate that can be easily administered orally, in particular for pediatric patients, and to the extremely poor palatability of the products available on the market. The unpleasant taste and odor make oral administration of butyrate extremely difficult, especially in children. Thus, new formulations of butyrate with a better palatability, which can be easily administered orally, are needed. Another possible solution could be the modulation of intestinal microflora by probiotics. Probiotics are live and viable microorganisms, which, if given in adequate amounts, confer a beneficial effect to the host. Probiotic microorganisms generate small molecular metabolic byproducts, referred to as “postbiotics”, which exert beneficial regulatory influence on host biological functions, including butyrate[100].
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So, basically because it doesnt taste good and marketing for butyrate sucks.
Post Edited (PathogenKiller) : 4/15/2014 10:06:25 AM (GMT-6)