Significant strides in science and technology made over the past decade will be instrumental in our efforts to understand precision nutrition. In this next section, we discuss contributors to individual variability and precision nutrition, including the role of metabolism, genotypes, and the gut microbiome.Variability in responses to nutritional interventions in healthy humans is well-known and suggests that individuals may benefit from more personalized dietary regimens to improve or maintain health. Although the physiologic/genetic underpinnings of these phenotypes and their responsiveness to changes in nutritional status largely remain to be explored, tools to efficiently identify nutritionally responsive phenotypes are emerging. Variable responses to dietary omega-3 FAs are one of the better characterized nutritionally responsive phenotypes, and this research highlights the complexity and nuance needed to fully appreciate physiologically relevant responses. For instance, in a secondary analysis of a randomized, double-blind, placebo-controlled trial of short-term fish oil supplementation in 83 individuals of African ancestry, a two-thirds by one-third split in ‘high responders’ compared with ‘low responders’ was reported with respect to intervention effect on red blood cell long-chain ω-3 FA enrichment, reduction in plasma triglyceride concentrations, and stimulated monocyte inflammatory responses. Although an individual’s adiposity, baseline ω-3 FA status, consumed dose,dutch buckets system and the ingested ω-3 form contribute to the ω-3 response, this variance may also be influenced by an individual’s background diet. In particular, the consumption of less than one-third cup of dark-green and orange vegetables and legumes—and the health effects of their accompanying nutrients—was associated with the low response in a secondary analysis of the aforementioned intervention study.
Another experimental approach to examine inter individual variability to a nutritional intervention is the mixed meal/ macro-nutrient challenge test. Analogous to oral glucose tolerance tests, in which the metabolic response to a standardized carbohydrate challenge is investigated, a mixed macro-nutrient challenge can be used to probe the metabolic response to a complex meal. Using standard clinical measurements, such a challenge can be used to simultaneously assess insulin sensitivity and fat tolerance. However, by expanding the experimental end points to include both physiologic and broad metabolic responses using modern metabolomic technologies, the potential for phenotypic profiling of an individual’s response to such a standardized meal is extraordinary. For instance, an individual’s metabolic flexibility , their metabolic health, and the potential for their response to interventions can all be assessed. Another powerful application of metabolomic phenotyping in nutritional research is the application to twin studies. By employing sets of both dizygotic and monozygotic twins, these approaches have demonstrated the power to segregate and quantify the genetic and environmental factors driving covariance between physiologic and metabolic traits and health outcomes. In summary, characterizing the range and nature of both fasting and postprandial nutritional phenotypes based on differences in metabolism in healthy populations offers novel approaches to identify individuals that may benefit from more individualized nutritional guidance to improve and/or maintain their health. Moreover, tools exist today to begin this task. The application of these tools in well-designed clinical trials will be critical to effectively demonstrate their value in aligning nutritional guidance and/or interventions with metabolic phenotypes.
Throughout history, humans evolutionarily adapted to their local environments to move across the globe, including to their changing diets. However, transitions to the modern Western diet in the last 75 y have resulted in maladaptations leading to a high prevalence of various chronic diseases, including obesity, cancer, and cardiometabolic diseases that disproportionately affect certain populations and create ethnic health disparities. For example, the adoption of the Western diet brought about a dramatic increase in the intake of PUFAs, specifically dietary ω-6 PUFAs. This shift was initiated by an American Heart Association recommendation in 1961 to replace dietary SFAs with PUFAs. Evidence supporting the recommendation included randomized controlled trials and cohort studies conducted in non-Hispanic White populations showing benefits of increasing ω-6 PUFAs on levels of serum lipids and lipoproteins. It was also assumed that only a small proportion of these ω-6 PUFAs could be converted to proinflammatory/prothrombotic long-chain ω-6 PUFAs, such as arachidonic acid, so adding 5%–10% energy as ω-6 PUFAs would have limited detrimental inflammatory/thrombotic effects due to saturation of the biosynthetic pathway. However, studies began to emerge a decade ago that showed genetic ancestry plays a critical role in determining the metabolic capacity of the long-chain ω-6 PUFA bio-synthetic pathway. Specifically, several studies revealed that populations with African ancestry have much higher frequencies of genetic variants in the FA desaturase cluster on chromosome 11 that markedly enhance the conversion of dietary ω-6 PUFAs to the long-chain ω-6, arachidonic acid and proin- flammatory/prothrombotic oxylipins , and endocannabinoids metabolites.
This underlying pathogenetic mechanism potentially results in a higher risk of chronic disease in those of African ancestry compared with those with European ancestry.With few exceptions, ω-6 long-chain PUFAs, such as arachidonic acid are proinflammatory/prothrombotic, and ω-3 longchain PUFAs, such as EPA and DHA are anti-inflammatory/ antithrombotic. Given the fact that a much higher proportion of populations of African ancestry has the capacity to form higher levels of arachidonic acid and its metabolites from dietary ω-6 PUFAs, it might be expected that ω-3 long-chain PUFAs would have a greater capacity to balance the impact of high dietary ω-6 PUFAs in these populations. Among clinical trials carried out to date, the VITamin D and omegA-3 TriaL is of particular interest when considering African ancestry, as it included n ¼ 5106 African-American participants out of n ¼ 25,871 total participants. Overall, supplementation with marine ω-3 long-chain PUFAs failed to prevent CVD or cancer events among healthy middle-aged men and women over 5 y of follow-up. Although ω-3 long-chain PUFA supplementation failed to prevent CVD in the full group analysis, in a follow-up subgroup analysis, Manson et al. demonstrated robust risk reductions in AfAm . Similarly, subgroup reanalysis of the VITAL study data based on the FADS framework compared the Kaplan–Meier curves for the MI end point, faceted by fish consumption and the number of CVD risk factors, for both European American and AfAm participants. This reanalysis revealed a marked ~80% reduction in MI associated with ω-3 long-chain PUFA supplementation in AfAm participants with baseline CVD risk who did not consume fish. By contrast, and in accord with our FADS framework and the mixed distribution of FADS haplotypes in European American populations, these participants failed to benefit similarly, regardless of baseline fish intake or baseline CVD risk. Collectively, these data suggest that AfAm populations may benefit from ω-3 long-chain PUFA supplementation, and both ancestry and FADS variability should be factored into future clinical trial designs. Such heterogeneity in the FADS cluster and other genes should inform the design of future clinical trials and may offer the opportunity to personalize recommendations of long-chain ω-3 PUFA supplementation to individuals of different ethnicities.The human gut responds rapidly to significant changes in the diet, and long-term dietary habits can exert strong effects. The influence of dietary components has had a long history of impact on gut health and maintenance of high gut microbial diversity. However, the gut microbiomes in humans are highly diverse and variable among individuals. Moreover, the influence of specific dietary components on the gut microbiome community structure and microbial metabolic function may vary among individual microbiomes. Thus, diet–microbiome interactions are highly individual and idiosyncratic,dutch buckets especially over one’s lifetime. Myriad dietary compounds are known to modulate human gut microbiome structure and function, with impact on disease; among these, dietary fibers were first established for their protective effects against chronic disease at population scales, which are widely believed to be largely mediated by the microbiome. Although dietary fiber intake is widely associated with positive health outcomes, persistent public health and nutrition messaging in many such nations has made only modest gains in increasing consumption. Thus, dietary fibers remain, to date, the only microbiome-focused nutrient with established dietary guidelines for population-scale health. If populations are recalcitrant to increasing their overall fiber intake, dietary fiber-based strategies to improve health must seek to identify the fiber types most active in stimulating the appropriate microbiome responses to benefit host physiology. This is not trivial in that 1) as a category, “fiber” simply means the non–human-digestible plant components and includes a vast array of molecular structures, both soluble and insoluble; and 2) the mechanisms by which these divergent structures alter the structure and function of gut microbiota, thereby influencing health, are poorly understood. Coupled with the fact that many fiber intervention studies do not specify or characterize the fiber structures employed , it is very challenging to discern which structural variables are influential on the responses of gut microbiota, both in vitro and in vivo.
Consequently, the ways in which fiber structures differentially influence ecology in the gut and metabolic function suggest that specific fibers can be targeted to desirable microbial consumers, thereby potentially being health beneficial at much smaller daily doses and at population scales . Fiber polysaccharide structures contain a dizzying array of linkages among glycosyl residues that, in turn, generate strong differences in higher-order structure of these substrates. Because microbial carbohydrate-active enzymes are highly specific to the bonds they hydrolyze, differences in genome content or regulation of these carbohydrate-active enzymes can drive division of labor in degradation of polysaccharide consumption. The Lindemann laboratory at Purdue University has demonstrated that 1) metabolism of fibers is emergent across individuals but structural differences select for similar microbiota across donors and 2) polysaccharides can structure communities and maintain diversity against high-dilution pressure. These data strongly suggest that fiber fine structures are highly selective for consortia of fermenting microbes and sustain them in diverse communities, potentially serving as a basis for targeting these microbiota in the midst of complex and idiosyncratic human gut communities. The hypothesis is that there are general ecologic strategies that microbes use to gain advantage with respect to fiber fermentation and possible downstream health benefits. It is believed that these strategies are genetically encoded; thus, they provide a foundation for engineering fibers that will allow the gut microbiome to be manipulated for predictable outcomes across disparate individuals. To test the hypothesis that subtle differences in polysaccharide structure select for distinct microbial communities, 2 subtly different model polysaccharides, red and white sorghum arabinoxylan were fermented with identical microbiota. RSAX was slightly more complex at the level of branching diversity than WSAX and maintained a more diverse microbiome in which members of Bacteroides spp., especially B. ovatus, were dominant. In contrast, WSAX promoted the growth of Agathobacter rectalis and Bifidobacterium longum-dominated communities. Interestingly, these polysaccharides selected forgenomically identical strains across 3 unrelated donors. Alongside the differences in community structure, RSAX and WSAX were fermented to different metabolic outcomes. Further, when fed to mice, WSAX and a human-derived microbial consortium adapted to its use modified the cecal metabolism of mice in sex specific ways. Interestingly, the effects of transient human microbes could be seen in metabolite profiles and in post antibiotic community resilience in the mice. Our data suggest that 1) polysaccharide fine structure deterministically selects for fermenting communities; 2) fine polysaccharide variants often target largely the same microbes across individuals; and 3) in turn, these differences lead to divergent metabolic outcomes, which are potentially impactful on host physiology and resilience to stress. Together, these results suggest that well-characterized fiber structures may be used to influence human health at population scales and relatively small doses.Tree death is a natural part of forest dynamics , but increasing rates of mortality can result when climatic conditions exceed a species’ physiological threshold . Although directional climate change has historically resulted in shifts in the distributions of species and ecosystems , comparatively rapid shifts in tree distributions attributed to anthropogenic climate change have been documented on all six plant-covered continents . Recent research has focused predominantly on causal mechanisms of tree death, feed backs to the climate system, and predictive modeling . Ecologists generally agree that trees and forests in temperate regions will shift to higher latitudes and upward in elevation due to warming trends . However, understanding how forests will behave at the ‘‘trailing ends’’ is limited . Stand development patterns following forest mortality events are of considerable interest because they indicate future structure and composition of affected forests, and the ability of these forests to maintain biodiversity and other ecosystem services . Although widespread mortality events can have negative impacts to ecosystem services , there may be benefits that are also important for adaptation in the human dimension .