Down to record depths in the human gut microbiome

By
Henrik Larsen
Research Story

A large international team of researchers has investigated the extent to which our genes determine bacterial composition in our digestive system. Their results are surprising. Samples taken from Danish children were included in the study.

If you take a faecal sample from one person and compare with a similar sample from a second, third and fourth individual, a picture of bacterial diversity will begin to emerge.

Some bacterial species will crop up in everyone’s gut, and most adults will have around the same amount of bacteria in their gut – approximately a kilo.

However, from person to person, there will usually be more differences than similarities in the composition of gut flora, which is made up of hundreds of different species of bacteria and also known as the human microbiome.

Science has pondered why this should be the case for almost two decades. During this time, scientists have explored the possibility that the human microbiome could be regulating everything from obesity to cancer, diabetes and psychiatric disorders.

In an attempt to find answers, an international research team with more than 100 participants began to analyse biological samples taken from 18,000 individuals from countries such as Finland, Israel, the USA, Canada, South Korea, Sweden and Denmark.

The result was the world’s largest and most extensive study in the field to date – and it was recently published in the prestigious scientific journal Nature Genetics.

Samples were taken from all age groups – from the youngest to the elderly – and Denmark provided some of the children’s samples.
The researchers had a DNA profile, in the form of a blood sample, and a faecal sample from each of the 18,000 participants.
The task was then to examine whether genetics – our hereditary traits – determine bacterial composition in our digestive system.

A number of Danish researchers contributed to the study, including experts from the University of Copenhagen and from Bispebjerg and Frederiksberg Hospital.
In addition, Lundbeck Foundation researchers from the Copenhagen Prospective Studies on Asthma in Childhood participated in the analysis of samples from 380 children aged between four and six from the so-called Mother-Child Cohort, COPSAC2010.

Very few genes gave a result

The researchers compared more than two million genetic variants in every single blood sample with the individual’s gut microbiota profile. Jakob Stokholm explains that, since they performed this enormous task for each of the 18,000 sets of samples, a bigger picture emerged.

Stokholm is a senior researcher at the Copenhagen Prospective Studies on Asthma in Childhood, and together with bioinformatician Shiraz Shah, among others, he analysed the samples from the 380 Danish children.

The study was able to identify 31 genetic variants affecting the bacterial composition of our gut, including the lactase gene which determines our tolerance to dairy products. But we have to say that the study indicates that diet and environmental factors have a major impact on the composition of the human gut microbiome
Jakob Stokholm

This knowledge could prove to be highly significant in terms of development of disease in children:

‘We know from other studies that environmental stresses at an early age – including contact with siblings, delivery by caesarean section and diet – have a huge impact on the development of the microbiome in children. So, following on from this new study, it would be logical to take a closer look at how genes and the gut microbiome potentially collaborate to contribute to development of asthma and other types of disease in children.’

The team

The research team at the Copenhagen Prospective Studies on Asthma in Childhood included: Shiraz Shah, Jonathan Thorsen, Jakob Stokholm and Professor Hans Bisgaard, head of the COPSAC study