Scientific Background

Immunity and Metabolism

Over millions of years, evolution has honed human immunity and metabolism, selecting for robust defense systems against pathogens and efficient energy storage during times of food scarcity. Infections were once the primary cause of death in humans, prompting the development of effective anti-microbial immunity that tightly integrates with the metabolic system. However, with the advent of modern medicine and improved living conditions, the dynamics of human health have drastically shifted.

In Western societies, non-infectious or non-communicable diseases (NCDs) have taken the forefront, driven mainly by lifestyle-related factors such as metabolic risk, sedentary behavior, and obesity. This shift is evident in the decline of infectious diseases as a cause of death from 75% to below 15%, while NCDs now account for over 80% of deaths in developed countries.

Figure based on Finch and Crimmins, 2004
Non-communicable, lifestyle-dependent diseases

The increase in life expectancy in Western societies is a testament to medical advancements and improved living standards, but it comes with a new set of health challenges. The emergence of NCDs, including gout, type 2 diabetes, obesity, cardiovascular disease, and neurodegenerative conditions, has begun to impact both healthspan and longevity. Alarming trends indicate a decline in life expectancy in certain regions, with lifestyle-associated diseases taking a toll on the current generation and possibly worsening in the future.

Figure based on Finch and Crimmins, 2004

The situation is further complicated in low-income and middle-income countries, where the double burden of malnutrition prevails. Here, undernutrition and obesity coexist due to changes in food systems, increased availability of processed foods, and reduced physical activity. The consequences of this double burden of malnutrition are likely to amplify the appearance of nutrition-related NCDs, posing a significant challenge for public health efforts.


A critical concept to understand in this context is "metaflammation."
Unlike acute inflammation associated with infections, metaflammation is a chronic low-grade inflammatory state triggered by various lifestyle and environmental factors.
Obesity, overnutrition, sedentary lifestyles, aging, stress, and sleep deprivation can all contribute to metaflammation.
As this form of inflammation lacks overt symptoms, its detrimental effects on cellular and organ function often go unnoticed.

Figure based on Egger and Dixon, 2009, 2014; Kovtonyuk et al., 2016; Latz and Duewell, 2018
SFB 1454

To address the growing burden of NCDs, SFB 1454 is delving into the underlying triggers and cellular programming of metaflammation. By adopting a systems-based approach, we aim to develop holistic strategies that encompass both pharmacological interventions and lifestyle modifications. The integration of digital health applications as preventive tools holds promise for promoting healthier lifestyles and reducing the prevalence of lifestyle-associated diseases.

In conclusion, the evolutionary journey of humans has seen a profound transformation in disease patterns, from infectious threats to lifestyle-associated diseases. Understanding and combating metaflammation is a key focus in unraveling the complex web of factors driving NCDs. With collaborative efforts, innovative interventions, and a broader understanding of the interplay between immunity, metabolism, and lifestyle, we can pave the way for healthier and longer lives in the modern era.

Figure: Focus areas of the different research projects within SFB 1454.