Enhancing Gut Health in Transition Cows Anne H. Laarman, PhD - PowerPoint PPT Presentation

Enhancing Gut Health in Transition Cows Anne H. Laarman, PhD Assistant Professor, Dairy Nutrition & Physiology 23-25 January 2020

Overview  Transition Period  Challenges to Gut Health • Rumen • Hindgut  Enhancing Gut Health • VFA Absorption • Microbial Supplementation

Transition Period  Negative energy balance linked to metabolic diseases and resumption of cyclicity

Transition Period  Additional changes • Diet fermentability • Absorptive surface area • Microbiome  Timeline for adaptation often not completely considered

Rumen Physiology Fermentation Feed Products Microbiome Rumen Epimural Microbiome Host Proteome Epithelium Blood Lower Gut Signals

Transition Cow Rumen Microbiome High grain diets decrease bacterial:  • Number • Richness Hook et al., 2011 • Diversity Plaizier et al., 2017

Bacterial Species Abundance Minuti et al., 2015

Overview  Transition Period  Challenges to Gut Health • Rumen • Hindgut  Enhancing Gut Health • VFA Absorption • Microbial Supplementation

Subacute Ruminal Acidosis  US impact of $750m - $1.5b annually in lost milk production and increased culling • Number: 9.8m cows (USDA, 2018) • Incidence: 20-40% (Garrett et al., 1997) • Cost: $400 per case (Stone et al., 2004)  Increase in NFC in early lactation diets

Subacute Ruminal Acidosis  Transition to high grain compromises barrier integrity Steele, et al. 2011

Subacute Ruminal Acidosis  VFA required for epithelial damage Meissner et al., 2017

 Passive diffusion uncontrollable acidification of epithelial cells Laarman, 2015

Immune Response Inflammation initiators  • Pro-inflammatory cytokines (TNF- α, IL1- β , IL-6) • Anti-inflammatory cytokines (IL-10) • LPS Recognized by receptors  • TLR-2 (Gram-positive) • TLR-4 (Gram-negative) Activates inflammation cascade (NF- κ B)  • More cytokines • Acute phase proteins (Haptoglobin, SAA)

LPS/LBP TLR4 Complex LPS Immune Cell Gut Lumen Liver ↑ Inflammatory response ↑ Acute Phase Proteins: LBP • Serum Amyloid A • Haptoglobin （ LBP=LPS ） • LBP Portal Circulation (Courtesy of Dr. Sara Kvidera)

LPS & Barrier Integrity  LPS increases permeability of tissue at low pH Emmanuel et al., 2007

Barrier Integrity  Multi-layer vs. single-layer epithelium Steele et al., 2016

LPS Production During SARA Time below Rumen LPS Serum haptoglobin pH 5.6 (min/d) (EU/ml) (µg/ml) Control 161 a 29,933 a 0 a SARA (grain) 337 b 179,762 b 608 b SARA (alfalfa pellet) 510 b 169,266 b 21 a  SARA produces LPS  Not every SARA incident causes inflammation Khafipour et al., 2009

 Site of starch degradation major factor to consider • Rumen • Small intestine • Large intestine Zebeli et al., 2015

Hindgut Acidosis  Hindgut highly efficient at fermenting carbohydrates not previously fermented • Abomasal infusions of neutral-detergent soluble fibers not detectable in feces  Hindgut will see build-up of VFAs • Hindgut pH decline often absent • Acute phase response inconsistent Gressley et al., 2011

Hindgut Acidosis Control SARA SARA (Grain) (Alfalfa) Hindgut LPS, EU/ml 18,289 b 15,631 b 128,566 a Starch, %DM 2.8 b 2.6 b 7.4 a  Increasing dietary starch affects entire gut (Li et al., 2012)

Hindgut Acidosis Low Concentrate High Concentrate  Hindgut acidosis can cause epithelial integrity loss and NF-kB activation (Tao et al., 2014)

Summary  Rumen-degradable starch can cause SARA • Low rumen pH • LPS release • Pro-inflammatory response  Shifting fermentation to hindgut has trade-offs • More susceptible to LPS translocation

Overview  Transition Period  Challenges to Gut Health • Rumen • Hindgut  Enhancing Gut Health • VFA Absorption • Microbial Supplementation

24 VFA Absorption is Key Nutrient Acidosis - Acidosis- P Uptake Resistant Susceptible Acetate 7.40 ± 0.95 a 3.16 ± 0.75 b < 0.01 Butyrate 13.71 ± 1.10 a 8.77 ± 1.03 b < 0.01  Faster VFA uptake makes ruminants more resistant to subacute ruminal acidosis Penner et al., 2009

VFA absorption through passive diffusion and protein-  mediated flux

26 VFA Absorption Kinetics Changes in VFA absorption can be mediated through both  absorption avenues Laarman et al., 2016

Measuring VFA Transport Capacity Control Treatment

28 VFA Absorption Capacity  Changes in transporters explain changes in absorption Laarman et al., 2016

Improving VFA Absorption Capacity Butyrate @ 2.5% DMI (n=8) Calcium salt, ruminally dosed 2x daily Control (n=8) Grain Supplement (n = 16) Day -2 -1 1 2 3 4 5 6 7 Laarman et al., 2013

VFA Transporter Abundance VFA absorption capacity can be modulated dietarily  • Absorption capacity linked to cellular function Laarman et al., 2013

Beyond VFA Transport  Butyrate decreases immune and inflammatory response • Decreases NF κ B expression  Increased energy mobilization in rumen epithelium  Optimal inclusion rate unknown Dionissopoulos et al., 2013 Laarman et al., 2013

Summary  VFA absorption is key to resistance to SARA • Passive diffusion and protein-mediated absorption mechanisms  VFA absorption capacity can be manipulated through diet • Linked to cellular homeostasis • Likely multiple supplements and strategies

Overview  Transition Period  Challenges to Gut Health • Rumen • Hindgut  Enhancing Gut Health • VFA Absorption • Microbial Supplementation

Fermentation Products  Lactobacillus spp. fermentation product changed fermentation profile • Increased growth in beef steers by 0.10 kg/day Hall et al., 2018

Probiotics and Diet Adaptation  Active-dry Saccharomyces cerevisiae can aid adaptation to high grain diet AlZahal et al., 2014

Probiotics and Diet Adaptation  Saccharomyces cerevisiae improved rumen pH stability AlZahal et al., 2014

Probiotics and Transition Cows 30 Dry Matter Intake, Kg/d 25 20 15 P Values Trt 0.35 10 Week < 0.01 Parity < 0.01 5 Trt * Parity 0.69 0 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 Weeks in Lactation CTRL - P DFM - P CTRL - M DFM - M  Saccharomyces cerevisiae boulardii (CNCM I-1077) Steelreath et al., unpublished

Probiotics and Transition Cows 60 * Milk Output, kg/d 50 40 P Values 30 Trt < 0.01 Week < 0.01 20 Parity < 0.01 Trt * Parity 0.42 10 0 0 1 2 3 4 5 6 7 8 9 Weeks in Lactation CTRL - P DFM - P CTRL - M DFM - M Steelreath et al., unpublished

Probiotics and Transition Cows 800 P Values Trt 0.01 750 Week < 0.01 Body Weight, kg 700 Parity < 0.01 Trt * Parity 0.51 650 600 550 500 450 400 -3 -2 -1 0 1 2 3 4 5 6 7 8 9 Weeks of Lactation CTRL - P DFM - P CTRL - M DFM - M Steelreath et al., unpublished

Probiotics and Physiology  Energy balance • Same energy intake • Increased energy output • Decreased energy mobilization  No change in serum glucose or NEFA  SCB can increase TLR4 during transition (Bach et al., 2018) • TLR4 linked to rumen acidosis resistance (Chen et al., 2012) Steelreath et al., unpublished

Summary  Both live products and fermentation products available • Much variability among products on market  CNCM I-1077 improves milk production in heifers and cows • Immune status currently unknown • Possible mechanism through Toll-Like Receptors

Overview  Transition Period  Challenges to Gut Health • Rumen • Hindgut  Enhancing Gut Health • VFA Absorption • Microbial Supplementation

Key Challenges to Gut Health  Ruminal starch degradation can lead to SARA • Low pH • High LPS • Inflammatory response  Hindgut acidosis can occur with undigested carbohydrates • Physiologically very different

Key Opportunities for Enhancement  Improving VFA absorption • Direct supplementation • Improving gut adaptation  Microbial supplementation • Live microbial products & fermentation products • Much variation among products

Going Forward  Improving product targeting • Optimal time and dose  Improving gut adaptation • Increasing VFA absorption • Improving cellular homeostasis abilities • Decreasing inflammation longevity

Acknowledgments  Students  Funding • Maddie Bennett • Corrina Cheatham • Maddi Degenshein • Rebecca Hiltz • Dana McCurdy • Rayne Roberts • Maeghan Steelreath Hatch NC-2040 • Ali Wolfe  UI Dairy Staff • Josh Peak • Derrick Mamer  Interns & Work Studies