Poo research reveals links between lifestyle and gut flora

Through the analysis of more than 1000 human stool samples, a team of researchers led by Professor Jeroen Raes (VIB/VUB/KU Leuven) has identified 69 factors that are linked to gut flora composition.

The Flemish Gut Flora Project, one of the largest population-wide studies on gut flora variation among healthy volunteers, has presented its first major results. These results provide important information for future disease research and clinical studies.

In 2012, the Flemish Gut Flora Project commenced its ambitious task of mapping the gut flora composition of around 5,000 volunteers in Flanders (Belgium). The purpose of this endeavour was to investigate links between human gut flora and health, diet and lifestyle.

Titled ‘Population-level analysis of gut microbiome variation’, Raes’ study 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.

“Our research has given us a tremendous amount of new insight into the microbiota composition of normal 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, analysing 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,” explained Raes.

Stool transit time showed the strongest association with gut flora composition. Diet was also an important factor, 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 and an association between gut flora composition and beer consumption.

Other project results incite deeper investigation, such as the relationship between 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 hayfever drugs and hormones used for anticonception or alleviation of menopause symptoms. Early life events, such as birth mode or whether or not volunteers were breastfed as babies, were not reflected in adult microbiota composition.

“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,” explained Raes.

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 key to advancing the field and speeding up the path to developing gut flora-based drugs.

“Such replication adds a tremendous amount of robustness to the results,” Raes emphasised. “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.”

Although the Flemish Gut Flora Project has enormously enriched our knowledge of gut flora composition, it only explains 7% of gut flora variation. An enormous amount of work still needs to be done in order to sketch out 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 VIB team revealed a wide range of associations, further research is required to unveil what is cause and what is consequence.

This is 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 willing to participate, the faster VIB will be able to unveil 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 to the Flemish Gut Flora Project are the heart of this study,” Raes said. “Without their enthusiasm, this couldn’t have been done.”

The project’s fundamental insights have been published in the journal Science.