BR 07-2 THE LINKING IN THE HUMAN (OBSERVATIONAL AND CLINICAL STUDY)

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Abstract

A number of chronic disease conditions tend to cluster in families with an increased risk in first-degree relatives, but also an increased risk in second-degree relatives. This fact is most often referred to as the heritability (heredity) of these diseases and explained by the influence of genetic factors, or shared environment, even if the more specific details or mechanism leading to disease are not known. New methods have to be explored in screening studies and register linkage studies to define and measure consequences of a positive family history of disease. Furthermore, recent studies have indicated that different genetic scores of well-known genetic markers of disease conditions such as obesity, type 2 diabetes or myocardial infarction are only able to explain a minor proportion of this described heritability. Thus, there is still a lack of knowledge to explain the so called “missing heritability” of these disorders [1].

Of particular interest in this perspective is to determine the role of the microbiome, measured as microbiota (the gut bacteria composition and variety, but also from the oral cavity), and its association with dietary intake together with the genetic profile of the host, in relation to alterations in metabolism and immunological function. For example, changes in microbiota composition has been associated with risk of obesity, type 2 diabetes and immunological disturbances as well as with chronic inflammation. This research is linked to other research areas in microbiology, nutritional sciences, technology and innovation for prevention. For example, functional food products can be developed and tailored to match the profile and needs of the individual. Of special interest in a family perspective is that the microbiome of individuals is influenced in early life, in the first place by the microbiota of the mother from exposure to the offspring during delivery and neonatal period. Later on this is influenced by more or less shared microbiota patterns in the household during childhood and adolescence due to cohabitation. It is hypothesized that microbiota profile as well as dietary intake patterns may cluster within families. Recently it was discovered that there is also a specific serum biomarker, the pro-atherosclerotic metabolite, trimethylamine-N-oxide (TMAO) that is able to reflect the gut microbiome and predict cardiovascular events [2]. TMAO can also predict prognosis in patients with congestive heart failure. Interventions to change the microbiota have provided promising results [3] and been described as a potential treatment target for cardio-metabolic disease. Such interventions should be based on the wider use of designed and tested functional food products as part of a healthy lifestyle in general. New findings hypertensive experimental animals and in human patients has revealed a special pattern of different microbiota patterns (dysbiosis) that differs from normotensive controls [4]. This could be linked to early life influences of other factors related to lifestyle in adult life. One idea is to test the influence of antibiotic treatment in these hypertensive individuals to see if vascular function can be improved and blood pressure lowered. We have to learn more about the gastrointestinal tract as potential initial organ of metabolic hypertension, as recently suggested [5].

In summary, the family clustering of cardiometabolic disorders is a well-known clinical observation, but still not fully understood. Genetic factors, even put together in a risk score, can explain just a minor proportion of the increased family risk. New discoveries linking gut microbiota to obesity and cardiometabolic risk conditions, including hypertension, could explain some of this increased clustering. Gut microbiota could potentially be influenced by functional food products and healthy lifestyle, providing a link to cardiovascular and metabolic prevention.

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