Using large-scale population research to identify what shapes a healthy gut microbiome

13 April 2022

People often talk about a healthy intestinal flora, but until now it has not been clear what a “healthy” gut microbiome actually means. Researchers from UMCG, Utrecht University and UMC Utrecht have now been able to properly determine the composition of a healthy gut microbiome through large-scale research in more than 8,200 Lifelines participants. The detailed analysis, reported in Nature, allowed the researchers to not only compile a deep catalog of the microbiome but also to indicate which gut microbes are associated with disease and which with health. Their study also shows that people living together in a household share a more similar composition and that sharing a living environment and lifestyle has a greater influence than our genetics. Interestingly, the composition of the microbiome is not only determined by current living conditions but also by past circumstances such as the urbanicity of one’s childhood home.

Dutch Microbiome Project

Changes in gut microbiome composition and function have previously been associated with a wide variety of human health disorders, ranging from gastrointestinal to liver and metabolic diseases to psychological disorders. While increased knowledge about the influence of gut bacteria has been driving the development of microbiome-targeting therapies, the question what constitutes a healthy intestinal microbiome remained unanswered. To resolve this, in 2015, UMCG researchers initiated the Dutch Microbiome Project in the Lifelines cohort. While many groups around the world are studying the microbiome, the unique population structure of the Lifelines cohort, which includes multiple generations from the same families, the very wide range of health and lifestyle phenotypes Lifelines collects and the willingness of participants to contribute to this research have made this cohort uniquely powerful world-wide.

Extensive analysis of microbiome composition

In the new study, the researchers generated and analysed one of the largest, multi-generational gut microbiome cohorts to date, determining the precise composition and function of the intestinal microbiome in more than 8,200 Lifelines participants from 2,756 families, including both participants in good health and those with a variety of diseases. All participants collected feces at home that was then retrieved and stored at -80°C to ensure uniform, precise analysis. Gut microbiome parameters were then compared to 241 health and lifestyle factors reflecting physical and mental health, medication use, nutrition, socio-economic factors, location of childhood residence and current household makeup.

Distinct microbiomes associated with disease and health

The research confirmed that multiple bacteria in the gut are associated with many different diseases, such as mental disorders and gastrointestinal diseases. Remarkably, however, the researchers found that similar patterns of bacteria in the microbiome are related to very different diseases that do not co-occur and that affect different organs. The existence of this general pattern in the “unhealthy” microbiome across differing diseases enabled the researchers to establish the pattern and characteristic features of a “healthy” gut microbiome.

Determining factors of a healthier gut

The researchers also looked at which factors influence microbiome composition because these may represent routes to modify the gut microbiome for better health. Beyond previously known factors such as diet, use of certain medication and disease, they identified other influential factors. The intestinal flora was healthier if someone lives in a greener and less polluted environment with less small particulate matter in the air. Circumstances of childhood living space were also found to have an influence on gut microbiome and health in adulthood. For example, participants who reported having parents who smoked or who lived in an urban area as a child showed less healthy effects in their intestinal microbiome.

Joint household is a determining factor

Heredity does not appear to be the greatest determinant of gut microbiome composition. The study found that lifestyle and living environment had a greater influence. People living together in the same household showing a higher similarity in their microbiome compositions, whether they are related or not. For family members who had stopped living together, the similarities in their gut flora decreased over time. However, benefitting from the familial structure in Lifelines, the researchers could narrow down some bacteria (about 15%) that do show a stronger effect of genetics, and these remained more similar in genetic relatives even after many years of living apart.

Healthy intestinal flora

The results of this very comprehensive study provide a deep catalog of the microbiome and the factors that influence its composition that can be the basis for developing therapies that target the microbiome.

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