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6. Closed Conversation - Postbiotic_Differentiation Feedworks_2022.pptx
- 1. This document is provided to you, at your request, for informational purposes only. These materials do not, and are not intended to, constitute veterinary, legal or regulatory advice. The information contained in this document is based on publicly available sources and/or unpublished data and is believed to be true and accurate, but Diamond V does not guarantee or make any warranty of accuracy or completeness. Legal and regulatory compliance for your business is your responsibility. The purchaser/user assumes all risks relating to the use of the information contained herein, and agrees that we are not liable to you or any third party relating to the use of such information. We recommend you consult animal health, regulatory and legal advisors familiar with all applicable laws, rules and regulations. Postbiotics Dr Curtis Harms DVM Feedworks Conference September 2022
- 2. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Postbiotic Definition?
- 3. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use 3 “A preparation of inanimate microorganisms and/or their components that confer health benefits on the host” ISAPP Definition Postbiotic Salminen, S., Collado, M.C., Endo, A. et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol (2021). Diamond V® postbiotic is produced during our highly controlled fermentation process in our state-of-the-art manufacturing facility. preparation The cells remaining after fermentation are completely inanimate — killed by thermal processing. inanimate microorganisms components All metabolites produced during fermentation and cells used are in Diamond V® postbiotic — nothing is filtered out or isolated. confer health benefits on the host Diamond V® products have been researched in hundreds of animal studies and peer-reviewed publications. Coupled with multiple human clinical trials, this research demonstrates Diamond V® postbiotic supports immune and gut health.
- 4. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use What’s the Difference? Prebiotic, Probiotic, and Postbiotics Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use
- 5. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Prebiotics
- 6. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use No – compounds can influence a wide array of microbes in the animal gut—without an exact match. Yes – to be effective, compounds must come in contact with specific microbes. Some – contains prebiotics as well as signaling molecules that directly influence microbes and host physiology. Yes – microbes in the gut must ferment, metabolize, or utilize prebiotics for the animal to receive benefits. Prebiotics VS Compounds that are highly selective and directly stimulate specific microbes, enhancing microbial communities. Fermentation product that directly influences gut microbes, supporting gut health and immune strength, resulting in performance. 6 Metabolism required? Narrow Range?
- 7. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Probiotics
- 8. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Yes – direct product research shows effect on innate and adaptive immune system. Somewhat – some components are shown to stimulate innate immunity (but product-specific studies are lacking). Yes – a 2-year shelf life and shown effective after pelleting and extrusion at +100°C (212°F). Not always – live products may not survive storage, transport, pelleting, extrusion. Yes – Diamond V fermentation process and raw ingredient sources are highly controlled. Not always – may be made with wide variation of by-products from other industries. Probiotics, Live Yeast, DFMs VS Live organisms fed to support gut health, microbial balance, and immune function. Fermentation product fed to support gut health and immune strength, resulting in performance. 8 Modulates immunity? Consistent? Stable?
- 9. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Antibiotics
- 10. © Diamond V, Inc. All rights reserved. XPC Antibiotic S. Typhimurium; Ampicillin Original XPC Has No Direct Antibiotic Activity 10 Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use
- 11. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Confer health benefits on host
- 12. © Diamond V, Inc. All rights reserved. Diamond V Original product “Helps support dry matter intake (DMI) of dairy cows when fed as part of a total mixed ration during the first 70 days of lactation” 12 FDA Functional Claim Don’t forget the benefits with Repro – BCS, energy balance. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use
- 13. © Diamond V, Inc. All rights reserved. Meta-Analysis Summary Results Poppy et al., 2012. J. Dairy Sci. 95: 6027-6041 Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use
- 14. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Health outcomes with Diamond V.
- 15. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Reduce Lung Pathology 15 & Control FOR_DA423: Mahmoud et al., 2020
- 16. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use No Fever 101.5 102.5 103.5 104.5 0 5 10 15 20 25 Rectal Temperature (°F) Days Post-infection Control Calf Program P < 0.05 Fever FOR_DA411: Brewer et al., 2014
- 17. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Weeks Post- Calving Control Rumen Microbial Resilience Under Stress Phylum Firmicutes represents about half of rumen bacteria Diet induced lactic acid build up in rumen; twice sampled during week of diet change Guo et al., 2018. (DA034-a2) Diet Change1 Diet Change 2 1st week post-calving NutriTek -4 0 5 8 12 1 3 2 4 6 7 9 10 More Resilience to Stress = More Stability 17
- 18. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use White Blood Cell Response Vailati-RIboni et al., 2019 (DA332) Fewer White Blood Cells = Less Energy Spent 18 0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0 -2 3 8 13 18 23 28 33 SCS, Challenged Quarter Hours Relative to the Challenge Control NutriTek Challenge Phase 2, trt * time, P=0.29 1,076,592 SCC 179,415 SCC
- 19. © Diamond V, Inc. All rights reserved. Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use Mastitis Challenge & Milk Recovery Vailati-Riboni et al., 2019 (DA332) More Energy for Performance 19 30 40 50 60 70 80 90 100 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 Daily Milk, lbs/d Day of Study Control NutriTek Challenge Recovery Phase 2, trt * time, P=0.08
- 20. © Diamond V, Inc. All rights reserved. Diamond V Key Differentiators 20 Processing and shelf stable (2yr) Supports gut microbes Supports gut tissue integrity Supports mucosal immunity Supports immune response • Bacterial response • Viral response Consistency Breadth and depth of research Multi-system effects Confidential — Feedworks Conference September 2022 — Not For Distribution or Commercial Use
- 21. © Diamond V, Inc. All rights reserved. All label claims must meet the laws and regulations of each state or country where the product will be used. This presentation and the information described are not label claims or intended to imply that Diamond V products can be used to diagnose, mitigate, treat, cure, or prevent disease.
Editor's Notes
- fermentable oligosaccharides, disaccharides, monosaccharides and polyols, which are short-chain carbohydrates (sugars) that the small ... FODMAP is diets for IBS - simple carbohydrates.
- Prebiotic – are fiber like sources, grains, garlic, onions, artichokes. And oligosaccharides like MOS. Mos is a component of a yeast cell. 100g of yeast – 25% of cell wall. 75% is extract make foods more flavorful. ( to be used in food products) 6.25g or (25%) is MOS and another is 6.25g of betaglucan. Probiotic – live organisms DFM – live year that act as factories to produce make metabolites. Postbiotic – is the fermentation within a control environment with constant results. Microbes population, gut health and immune function 70% of the immune system is in the gut. - like less sick days, quicker recovery. --- **IMPORTANT NOTES FOR PRESENTER** How this slide is organized Top – product definition Middle – key differentiators Left – Competitor for each differentiator Right – Diamond V for each differentiator Bottom – Relevant Diamond V product research How to talk through this slide Start at top with product definition for competitor (left) then Diamond V (right) First key differentiator (middle), then how the competitor performs (left) then Diamond V (right) Next key differentiator: middle, left, right
- XPC has no direct effect as an antibiotic. We can clearly see the zone of inhibition here with the antibiotic but no inhibitory effect from the disc of XPC.
- Key points: “FDA Reviewed and Accepted”, the term of “FDA approved” applies only to drugs claim.
- Representative images of lungs at necropsy
- In the Brewer study, rectal temperatures and diarrhea were monitored in the calves on day 0 to day 21 post-infection. In this study, fever was observed less frequently (P < 0.05) in calves fed the Diamond V Calf Program. The largest differences for rectal temperatures were observed on day 3 to day 5 post-infection (38.8-39.0 °C). What does this mean clinically for the calf? With a fever there is a negative feedback to the appetite center of the brain. So we have a calf with an activated immune system and increased energy requirements, that now does not want to eat. Improved intakes is a big part of improved health and lessening the severity of the disease and improved recovery from a challenge.
- This study further demonstrates DV’s next generation products ability to stabilize microbe populations under stress ORIENT TO SLIDE Here you see trends in Firmicutes populations in transition cows Firmicutes are Phylum of gram positive bacteria Make up 50% of total rumen population There are three periods of stress Calving And 2 periods of diet induced SARA The black line shows how stress impacts bacteria populations in Control cows CLICK NutriTek fed cows have more stable rumen populations – even during stress Methods Cows from transition through early lactation Three stress events 1) Calving/shift from pre-partum to post-partum diet Post partum diet (lactation diet) 45% concentrate (DM basis) + assigned treatment 2 & 3) diet-induced SARA events SARA was induced with a gradual shift in diet over three days (Friday, Saturday, and Sunday) Grain-based SARA challenges were conducted during wk 5 (SARA1) and wk 8 (SARA2) of lactation by replacing 20% of the DM of the lactation TMR with pellets containing 50% ground wheat and 50% ground barley. After SARA events, cows were switched back to the lactation diet + assigned treatment Sampling occurred Weekly during non-SARA events – Friday Twice during SARA events Sample 1 on Tuesday Sample 2 on Friday NOTE: Graph is condensed and expanded Condensed weeks -4 to 0 and 10-12 Small gradual change Expanded weeks 5 and 8 Abrupt change following SARA event 2 samples taken compared to weekly sampling on others ——— **Background—additional notes from researcher** This graph shows longitudinal shifts in Firmicutes proportion in the rumen microbiome. On the X axis, there are different time points relative to calving, and on the Y axis we have OTU (Operational Taxonomic Unit) counts. The light color lines represent individual cows in each group. The bold lines are the fitted lines with the red indicating NTL (NutriTek) and blue indicating Con (Control). Overall, Con group experiences more fluctuation during the periods that animal is exposed to physiological challenge, such as stressors in the first week post-calving and follow up SARA challenges. However, NTL group went through the challenge periods without significant population shift (Rumen resilience). *A majority of metagenomic analyses are carried out using 16S rRNA sequencing in order to assign operational taxonomic units (OTUs) in the form of species, genera or phyla. 19g NT dosage
- Transition We ran a challenge trial to clinically evaluate the effect of NutriTek on immune response in mastitis challenged cows Methods Half cows on NutriTek, half on control Challenge Day 45 of trial One-quarter with Strep uberis Measured immune response & production recovery Results Cows fed NutriTek had much lower somatic cell count Delayed onset From the challenge line, you see Control starts trending up at 13 hours after challenge NutriTek doesn’t start trending up until 22 hours Innate immune system held off clinical infection for 9 hours longer **Click** Reduced severity By 30 hours, there was a 900,000 cell count difference Biologically, we’d expect these animals to have a quicker recovery, but in this trial, all animals received antibiotic treatment after 30 hours (when biopsy was performed) ——— NA Reference **Background – Why use Strep?** Why use Strep? This was set up as a clinical trial Strep uberis is the model that is most well documented and reliable for use in clinical trials and challenge studies Using a proven method gives a higher degree of confidence that the results are real **Background — Somatic Cell Linear Score** Calculated as = log2(SCC/100) + 3 Reported from researcher Somatic cell counts increase with the severity of udder infection. However, the corresponding milk loss does not increase at the same rate. Somatic cell linear scores simplifies the prediction of milk loss. The relationship between lactation milk loss and linear scores above 2.0 is a straight line. For 2nd+ lactation animals, each LS above 2 indicates 200 kg of lactation milk lost LS 3 -> 200 kg lactation milk loss LS 4 -> 400 kg LS 5 -> 600 kg For 1st lactation animals, loss is estimated at half of older cows at each LS LS 3 -> 100 kg LS 4 -> 200 kg LS 5 -> 300 kg References http://www.agromedia.ca/ADM_Articles/content/dhi_scc.pdf Fetrow et al., 1988
- Transition Recovery from challenge is especially important in lactating cows Method Half cows on NutriTek, half on control Challenge Day 45 of trial One-quarter with Strep uberis Measured immune response & production recovery Results Pre-challenge, NutriTek fed-cows similar to Control Numerically higher milk NOT STATISICALLY HIGHER Click After challenge this is what we see NutriTek fed cows recovered much more quickly than the Control-fed cows Less energy spent on immune response Less damage to mammary secretory tissue because the white blood cells (somatic cells) in the cows fed NutriTek more effectively killed the bacteria, and also because genes that protect the mammary secretory cells when an infection occurs were up-regulated in the NT fed cows. Less loss of production in the face of the challenge This difference is observed EVEN though this study was not powered for production – only 8 cows ___ NA Reference
- TRANSITION So how do Diamond V products compare to other feed additives? TALKING POINTS When you look across all of the categories of additives, only Diamond V can claim all of these benefits Processing and shelf stable – many other additives in the marketplace are not stable in pelleting, extrusion, or even on the shelf. Consistency – Diamond V’s highly controlled manufacturing process provides lot-to-lot consistency that many other additives cannot Multi-system effects – Diamond V’s products are a combination of many metabolites and compounds, which account for the extensive benefits we see in animal Breadth and depth of research – Diamond V leads the industry in in-animal (in vivo) research **CLICK** And because our products have a unique combination of hundreds of compounds, our products are the only ones that can provide the digestive health and immune support; our research has shown that our products Supports gut microbes – Diamond V’s products are shown to support beneficial microbes and promote diversity, which provides stability in times of stress Supports gut tissue integrity – Diamond V’s products are shown to strengthen the protective barrier of gut epithelium; this strength has been demonstrated in cell culture and in reduction of LPS (endotoxin) in animal blood serum in times of stress Supports mucosal immunity – Animals fed Diamond V products have higher levels of secretory immunoglobin A (sIgA), and important antibody that is present in the mucosal lining of tissues and contributes to barrier protection Supports immune response – Animals fed Diamond V products have stronger responses to pathogenic compounds (bacterial and viral) and demonstrate faster recovery from challenges -- **IMPORTANT NOTE FOR PRESENTER** Typical benefits claimed Not an exhaustive list of benefits claimed by all products within a category These are claims only Not intended to validate whether the claims are met HOW TO USE THIS SLIDE Click on a specific feed additive to go to that product comparison slide. If you do not select a specific feed additive, you will advance to the comparison of Diamond V vs Other Fermentation Products and then the end of the deck.