Barry Bradford Barry Bradford completed dual bachelor s degrees at Iowa State University and a doctorate in animal nutrition at Michigan State

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1 Barry Bradford Barry Bradford completed dual bachelor s degrees at Iowa State University and a doctorate in animal nutrition at Michigan State University. In 2006 he joined Kansas State University as an assistant professor, and was promoted to associate professor in Bradford oversees an active research program and has published more than 50 peer-reviewed papers on the interactions of inflammation and metabolism, use of alternative feedstuffs in dairy cattle, and physiological regulation of carbohydrate and lipid metabolism. In addition, he teaches over 180 students per year in several undergraduate and graduate courses in animal nutrition and physiology.

2 How transition cow nutrient metabolism influences the immune system Barry Bradford Kansas State University 22 October 2015 Overview The problem with transition cows Nutrient effects on immune function Interacting mechanisms Take-home points The transition period The bar is being raised First lactation Third lactation ~ 4 metabolic ~ 6 infectious Diagnostic tools now give us the ability to detect disruptions that we would not have noticed a few decades ago. Example: transition dairy cows have worse lactation outcomes following: o Subclinical hypocalcemia o Subclinical ketosis o Subclinical metritis Ingvartsen, 2006 How important is immunity? Transition cows have decreased immune function Lymphocyte function Neutrophil function Goff and Horst,1997

3 Transition immune cells Enhanced inflammatory response Immunosuppression coincides with greater risk of infection Impaired chemotaxis Decreased phagocytosis Reduced killing ability Sordillo et al., 1995; Contreras et al., 2012; Kehrli et al., 1989; Nonnecke et al., 2003 Østergaard et al, 2005 Monocyte proliferation response to endotoxin Immune function predicts infection risk n = 7 n = 19 n = 5 Infections 16% 10*** Nutrition can directly influence: Metabolic health Gut health Microbial ecology Immune function Catalani et al, 2013 Nutrients implicated Vitamins Minerals Fatty acids Carbohydrates Amino acids Yup, that s pretty much all of them. Assessing adequacy Nutritional support of health can be difficult to assess Requirements are altered by physiological state Suboptimal nutrition may only cause problems during challenging scenarios

4 Responses may appear during a challenge Chromium limited weight loss due to endotoxin challenge Also enhanced feed efficiency in newlyreceived feedlot cattle A long term trend Dairy nutrition studies incorporating a challenge model Bernhard et al., 2012 PubMed: (dairy or Holstein) AND (cow or cattle) AND (dietary or diet or TMR or ration or feed or feeding) AND (health or challenge or stress or disease or transition) Diet gut health Metabolic function Fatty acids Glucose Steele et al., 2011 Fatty acids in transition cows BHBA ATP Lipid peroxide formation Lipid peroxides H ATP Chain reactions can lead to Membrane damage Protein damage DNA damage Cell death

5 Plasma TBARS, μm Increased lipid peroxides in overweight transition cows 3 * 2 Low BCS Mod BCS 1 High BCS 0 Precalving Postcalving Bernabucci et al., 2005 Vitamin E status declines during the transition period Weiss et al., 1990 Vitamin E status is decreased in cows with metabolic disorders Many factors may contribute to systemic inflammation 4 Plasma α tocopherol, mg/l 3 a 2 1 b b 0 Healthy DA + mild FL DA + severe FL Mudron et al., 1997 Interacting mechanisms 3.0 Infection Metabolic Odds ratio, subsequent risk of ketosis 4.0 Metabolic Infection Odds ratio, relative risk following ketosis The chicken or the egg? Early metritis Acute mastitis Chronic mastitis 0.0 Risk of metritis Risk of mastitis Gröhn et al., 1989 Duffield et al., 2009; Doohoo and Martin, 1984

6 BHBA decreases neutrophil function BHBA inhibits extracellular trap formation Grinberg et al., 2008 Grinberg et al., 2008 Dry matter intake (kg/d) Inflammation promotes ketosis Day of lactation Control 1.5 μg/kg TNF 3.0 μg/kg TNF P = 0.02, TNFα vs. control (18% decrease) Subclinical Ketosis 9% 27% 27% It s the chicken AND the egg Yuan et al., 2013 Unexpected benefits? Unexpected benefits? 6 6 P = Control Choline Cows were fed 15 g choline per day from 25 days before calving to 80 days in milk Control Choline P = P = P = 0.01 Ketosis Ketosis Mastitis Total morbidity Lima et al., 2012 Lima et al., 2012

7 Balancing for optimal health Example: Fiber for gut health vs. starch for glucose supply in lactating cows Fiber: Prevention of acidosis, more robust to dietary fluctuation Starch: Supports glucose production, helping to limit metabolic disease and support immune function Balancing for optimal health Example: Omega-3 fatty acids to support metabolic and immune function Evidence in nonruminants and limited data in ruminants suggests benefits of omega 3 supplementation, but... Delivering enough of these lipids without disrupting ruminal function is a challenge. Take home points Nutrients can influence gut health, metabolic health, and immune function, with overlapping roles. Requirements vary with physiological state of the animal, and nutrients may have no effect until a challenge is encountered. Creative approaches are possible, but effects on all aspects of health must be considered. Questions/comments: Barry Thank you!