PARTNERSHIP: ELUCIDATING GUT MICROBIOTA-DEPENDENT HEALTH IMPACTS OF HASKAP BERRIES TO INFORM AGRICULTURAL PRODUCTION PRACTICES THAT WILL MAXIMIZE BIOACTIVE POTENTIAL

Polyphenol-rich Haskap berries (Haskap) have untapped therapeutic potential to improvehuman health, and agricultural producers in northern U.S. states are poised to increaseproduction if consumer demand increases. This is important because inflammation andabnormal metabolism play a major role in the development and progression of manydiseases including type 2 diabetes, cardiovascular disease and cancer (1, 2). Therefore,identifying foods with bioactive components that decrease inflammation and improvemetabolism is an important strategy for reducing disease burden. Berries high inpolyphenols promote human health through a variety of mechanisms, includinginflammation lowering, that may be dependent on interactions with the gut microbiota. Weidentified gut microbiota dependent anti-inflammatory polyphenol breakdown productsfrom polyphenol rich berry juice in the blood of germ-free mice humanized with fecalmicrobial transplants from humans (Wilson et al.). Some of these bioactive polyphenolmolecules were measured in mice with a gut microbiota from a human donor with low butnot high inflammation levels, suggesting that the microbial digestion of polyphenols maycontribute, at least in part, to the difference in inflammation between the human donors.Haskap (Lonicera caerulea L.) are rich in anthocyanins and other polyphenoliccompounds (3). The long-term goal of this project is to form a partnership linking thehealth impacts of Haskap with varieties and management practices to maximizehealth-promoting compounds to benefit both consumers and producers. A criticalknowledge gap is that little is known about the interactions between gut microbes andHaskap polyphenols to produce bioactive metabolites linked to downstream healthimpacts. Additionally, we need to know which Haskap varieties and harvest timing willyield the greatest bioactive potential.To address this gap, we will investigate the interaction of bioactive components in Haskapwith gut microbiota and the resultant gut and serum metabolites, inflammation, andmetabolic health, and then couple this with analysis of berries from different Haskapvarieties and harvest times. Based on established gut microbiome differences betweenmetabolically healthy and unhealthy individuals (4, 5) and our findings that polyphenolrich juice was metabolized differently in mice humanized with a low versus highinflammation microbiota (Wilson et al.), we propose an analysis that will compare gutmicrobiota and health impacts of Haskap berry consumption between metabolicallyhealthy and unhealthy groups. One key characteristic of the metabolically unhealthygroup will be an elevated waist circumference, which corresponds with elevatedinflammation (6). This proposal will significantly advance research by 1) determining theinteraction between the gut microbiota and bioactive components of Haskap, 2)elucidating the microbiome dependent metabolic impacts of Haskap underpinningchanges in health and inflammation biomarkers, and 3) partnering with regional plantscientists to integrate metabolomic analysis of polyphenols within a variety of Haskapvarieties and growing conditions with human health outcomes to identify those with thegreatest potential health impacts. Our overarching hypothesis is that Haskap will lowerinflammation and improve metabolic health through gut microbiome dependentmechanisms. The following specific objectives are proposed:Objective 1: Determine the impact of Haskap on the gut microbiome and metabolome ina cohort of adults with both low and high risk of metabolic syndrome. Hypothesis: Theimpact of Haskap will be mediated by initial composition of the gut microbiome and thatHaskap will shift the gut microbiome and gut metabolites of the high metabolic syndromerisk adults toward those with low risk.Objective 2: Determine how gut microbiome composition and production of bioactivemetabolites from Haskap impacts serum metabolite, health, and inflammation biomarkersin a cohort of adults with both low and high risk of metabolic syndrome. This analysis willidentify the impact of individual differences in gut microbiome composition on theresponse to Haskap consumption. Hypothesis: Individual differences in response toHaskap consumption are mediated by composition of the gut microbiome and resultingmetabolite production in the gut.Objective 3: Identify Haskap varieties and growing practices that increase production ofhealth-promoting compounds. Previous research has demonstrated the concentration ofgeneral and specific polyphenols and in vivo anti-inflammatory and anti-diabetic activityin Haskap differ widely among varieties and harvest timing (fruit maturity). MSU-WesternAg Research Center will determine the effects of harvest timing on concentration andyield of health-promoting compounds in over twenty varieties of Haskap. Hypothesis:Varieties will differ in their concentration of bioactive compounds and the effects of fruitmaturity on these concentrations will be variety specific.