Valeric acid esters

This post expands on a very extensive study of broiler chickens conducted by scientists from Belgium and the Netherlands. Part of the motivation of this new supplement was the observation that valeric acid-producing Oscillibacter valericigenes is found to be more abundant in the stools of healthy people as compared to the stools of patients with Crohn’s disease. [1] The authors could have done a better job of explaining the role of glucagon like peptide 2. This post is probably also not doing such a good job either. Consult reference [2] for a good review. The major take home of this post is that the L-cells that secrete GLP2 do so by means of G protein coupled receptors of short chain fatty acids. Two of these also bind propionic acid. Another might be more selective for valeric acid.

GLP-2

SCFA data, villus height and crypt depth measurements, and density of GLP-2-immunoreactive cells were assessed by one-way analysis of variance (ANOVA) In a short review of a pig study, Estall and Druker remind us a few things about the glucagon like peptide 2. The first thing is that it’s receptor is a G protein coupled receptor, unlike the GLP-1 and glucagon receptors. [2] The L cell is an enteroendocrine cell that secretes glucagon. The next question would be, do these cells express free fatty acid receptors.

indeed, GLP-1 and GLP-2 secreting enteroendocrine L cells express short chain fatty acid receptors GPR41, GPR43, GPR119 and TGR5. In a study of airway epithelial cells GPR41 and GPR43 seem to prefer propionic acid to valeric acid. [3] GPR119 is more of an enigma with a vast array of ligands, most of which are longer chain than valeric acid. [4] TGR5 is the G protein coupled receptor activated by bile acids. It seems to have a role in linking the intestinal microbiome to non alcoholic fatty liver disease. [5]. Fecal microbial transplants are also mentioned in this review. This post will not get into the role of intestinal microbiome in deconjugating bile acids and whether valeric acid might either bind to TGR5 or have some less direct effect.

Villus tips and the food conversion ratio

The food conversion ratio, in the case of animals raised for meat,it is the ratio of mass of food intake divided by the mass of meat. The smaller the ratio is, the more efficient the use of food. Table 3 of Onrust 2018 has been trimmed down to show only the total time period. The trivalerate/glycerol esters of valeratic acid had no significant effect on food intake or weight gain per day but did have a significant improvement in final body weight and FCR. The length of villus height and the depth of the crypts less. [1]

.Pathogen challenges

Day-of-hatch Ross 308 broilers, 27 birds in each treatment group. These birds were regularly vaccinated on days: 4, 14, 16, 18, 19, and 20. On days 18, 19, and 20 the birds were challenged by an oral gavage of approximately 4 × 10⁸ cfu of C. perfringens strain 56 (3 times a day). At d 21, all birds were euthanized . [1]

1. no feed additive, n=27
2. no feed additive, + C. perfringens
3. GVA at higher concentrations (5.0, 2.5, 2.0 g/kg in resp. week 1, 2, 3) +C. perfringens
4. GVA at lower concentrations (2.5, 2.0, 1.5 g/kg in resp. week 1, 2, 3) + C. perfringens.

At necropsy lesions in the small intestine :duodenum, jejunum, and ileum.

• 0 = no gross lesions
• 2 = small focal necroses or ulcerations (1 to 5 foci)
• 3 = focal necroses or ulcerations (6 to 15 foci)
• 4 = focal necroses or ulcerations (16 or more foci)
• 5 = patches of necrosis more than 1 cm long
• 6 = diffuse necrosis.

potential scfa receptors on immune cells… not just L cells

• GPR41/FFAR3, also known as free fatty acid receptor 3, is mostly found in neutrophils and eosinophils
• GPR43 /FFAR2, also known as the free fatty acid receptor 2 is mostly found in neutrophils.
• There really isn’t any mRNA expression data on GPR119 on Protein Atlas.
• TGR5/GPBAR1 mRNA is found in various lineages of monocytes according to ProteinAtlas.org. According to Wikipedia authors, TGR5 controls macrophage supression by bile acids. Wikipedia authors cite references that TGR5 might be involved in some sort of tryroid hormone conversion that will not be addressed in this post.

Gastrivix™ Avi [6]

Gastrivix™ Avi is the only product combining the power of valeric acid with the well-known benefits of butyric acid both in form of esters. The product is suitable for the use in poultry with a dosage range between 250 g/ton to 500 g/ton of feed.

Unrivaled butyric acid power [7]

ProPhorce™ SR is the next generation of butyric acid products. It consists of butyrins – glycerol esters of butyric acid, which are not coated, but in ester form. You get the same well documented effects as with coated butyric acid products but with more “horse power” thanks to the esterifying technology. That means a lower dosage for the same results.

No conclusions…

The Onrust study was extensive and looks very promising. [1] Mechanistically they did do a great job of explaining GLP-2. The Estall and Drucker review is pretty good, [2] but it fails to give insight as to why to use the valeric acid ester feed supplement. Reviews [4] and [5] are staying on this post for now so they won’t be lost. Links to commercial animal feed products are in references [6[ and [7]

References

1. Onrust L, Van Driessche K, Ducatelle R, Schwarzer K, Haesebrouck F, Van (2018) Immerseel F. Valeric acid glyceride esters in feed promote broiler performance and reduce the incidence of necrotic enteritis. Poult Sci. 2018 Jul 1;97(7):2303-2311. PMC free article
2. Estall JL, Drucker DJ. (2005) Tales beyond the crypt: glucagon-like peptide-2 and cytoprotection in the intestinal mucosa. Endocrinology. 2005 Jan;146(1):19-21. PMC free article
3. Cani PD, Everard A, Duparc T. (2013) Gut microbiota, enteroendocrine functions and metabolism. Curr Opin Pharmacol. 2013 Dec;13(6):935-40. PMC free article
4. Cohen LJ, Esterhazy D, Kim SH, Lemetre C, Aguilar RR, Gordon EA, Pickard AJ, Cross JR, Emiliano AB, Han SM, Chu J, Vila-Farres X, Kaplitt J, Rogoz A, Calle PY, Hunter C, Bitok JK, Brady SF. (2017( Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature. 2017 Sep 7;549(7670):48-53. PMC free article
5. Chen J, Vitetta L. (2020) Gut Microbiota Metabolites in NAFLD Pathogenesis and Therapeutic Implications. Int J Mol Sci. 2020 Jul 23;21(15):5214. PMC free article
6. file:///C:/Users/Owner/Downloads/Gastrivix_Avi.pdf
7. https://www.perstorp.com/en/products/prophorce_sr_130