The Flemish Gut Flora Project has presented its first major results about the gut flora of healthy volunteers. By analyzing more than 1,000 human stool samples, a research team led by Professor Jeroen Raes (VIB/VUB/KU Leuven) has identified 69 factors linked to gut flora composition. Their results, published in Science, provide important information for future disease research and clinical studies.
In 2012, Professor Jeroen Raes initiated the launch of the Flemish Gut Flora Project, one of the largest population-wide studies on gut flora variation among healthy volunteers.Together with his team, Prof. Raes aimed at the ambitious task of mapping the gut flora composition of about 5,000 volunteers in Flanders (Belgium). The purpose of this endeavour was to investigate links between the human gut flora and health, diet, and lifestyle.
Gut flora composition linked to health, diet, and lifestyle
The team has identified 69 factors associated with gut flora composition and diversity. Most of these covariates are related to transit time, health, diet, medication, gender, and age. Integration of the Flemish Gut Flora Project results with other data sets gathered around the world revealed a set of 14 bacterial genera that make up a universal core microbiota present in all individuals.
Jeroen Raes: “Our research has given us a tremendous amount of new insights into the microbiota composition of healthy people like you and me. This makes the Flemish Gut Flora Project unique, since the majority of previous studies focused on specific diseases or featured a significantly smaller geographical scope. However, analyzing the ‘average’ gut flora is essential for developing gut bacteria-based diagnostics and drugs. You need to understand what’s normal before you can understand and treat disease.”
Beer and buttermilk
Stool transit time showed the strongest association with gut flora composition. Diet was an important factor as well, with most associations related to fibre consumption. One of the many surprising findings was the association of a particular bacterial group with a preference for dark chocolate. “The Belgian chocolate effect,” Raes laughs. “As many might expect, we also found an association between gut flora composition and beer consumption.”
Other project results require deeper investigation, such as the relationship between the gut flora and factors linked to oxygen uptake capacity. Medication also had a strong link to the gut flora profile. The Raes Lab researchers not only identified associations with antibiotics and laxatives, but also with hay fever drugs and hormones used for anticonception or alleviation of menopause symptoms.
Remarkably, early-life events such as birth mode or whether or not volunteers were breast-fed as babies were not reflected in adult microbiota composition.
Jeroen Raes: “These results are essential for disease studies. Parkinson’s disease, for example, is typically associated with a longer intestinal transit time, which in turn impacts microbiota composition. So to study the microbiota in Parkinson’s disease, you need to take that into account. These and many other observations can help scientists in their research into future therapies.”
A key factor in this study was the collaboration with the Dutch LifeLines study, which allowed the researchers to replicate their findings: more than 90% of the identified factors were also detected in the Dutch cohort. International collaborations like these are the key to advancing the field and speed up the path to developing gut flora-based drugs. “Replication makes our results much more robust,” Raes emphasizes. “Of course, we also found some differences between both cohorts. Believe it or not, but one of the important dietary covariates identified in the Dutch cohort was the consumption of buttermilk.”
Tip of the iceberg
Although the Flemish Gut Flora Project has enriched our knowledge about gut flora composition, its results only explain 7% of gut flora variation. An enormous amount of work still needs to be done in order to map the entire gut flora ecosystem. The Raes Lab estimates that around 40,000 human samples will be required just to capture a complete picture of gut flora biodiversity. In other words: we are only seeing the tip of the iceberg. And although the team revealed a wide range of associations, further research is required to unveil what is cause and what is consequence.
That’s why this first publication doesn’t mark the end of the Flemish Gut Flora Project. The Raes Lab is already planning follow-up studies, including new large-scale research projects that will explore the evolution of gut flora over time. More volunteers are now being recruited for this long-term study. The more people participate, the faster the researchers will gain new insights into the relationship between the trillions of microbes in the human body and our health. “The thousands of volunteers, pharmacists, and healthcare professionals that participated in the Flemish Gut Flora Project are the heart of this study,” Raes says. “Without their enthusiasm, this couldn’t have been done.”