It’s the inside that counts: quantitative microbiome profiling

18 March 2018
​Many illnesses – like Crohn’s disease – are associated with gut flora alterations. And not only the type of bacteria in our bowels, but also their quantity matters. Introducing Quantitative Microbiome Profiling, Jeroen Raes (VIB-KU Leuven Center for Microbiology) and his team take a leap towards the quantitative assessment of microbiome composition.

The changes in amounts of gut bacteria are usually described as proportional shifts in microbiome composition. “The problem with these percentages is that they cannot tell you whether a particular bacterium is actually becoming more abundant under specific conditions”, Jeroen explains. “A proportional increase in one species could just as well imply that other taxa are declining. This makes it very difficult to link microbiome data to health and diseases. With Quantitative Microbiome Profiling, we are one step closer to solving this issue.”

Risky business
The development of the new methodology was financed by a KU Leuven CREA grant, aimed at stimulating young scientists to explore groundbreaking, but also risky research lines. Gwen Falony, staff scientist in Jeroen’s lab, is one of those enthusiasts: “Creating new methods is always tricky: you never know if it will work until you try. Thanks to the CREA initiative, we were able to take a chance, which turned out to be quite successful.”

Quantitative Microbiome Profiling allows fast and accurate determination of the bacterial load in a fecal sample. Jeroen: “By parallelization of microbiome sequencing with flow cytometry enumeration, we generate true quantitative microbiome profiles expressed as numbers of cells per gram, rather than percentages. We hope this technique will put gut flora research on the fast track.”

Rooted in the flemish gut flora project
Essential for the interpretation of quantitative microbiome findings was the Flemish Gut Flora Project. In this population-wide monitoring study, Jeroen and his team collected over 3,000 fecal samples from healthy volunteers. Assessment of microbiome variation in a non-diseased population enabled the identification of a new, often disease-associated microbiota community type characterized by a low microbial load.

Postdoc Doris Vandeputte: “We found 50 times less bacteria in samples from patients suffering from Crohn’s disease compared to healthy volunteers, quite a spectacular result. Further research will be targeted at determining whether this actually causes such diseases, and if so, how to prevent it.”

A numbers game
During the Flemish Gut Flora Project, Jeroen and his team got unexpected help from university college PXL Hasselt. Jeroen: “Students and personnel voluntarily started collecting stool samples at the school. Their initiative has been essential to the success of our study. Indeed, to be able to conduct representative research, we need as many samples as we can get.” The same goes for our current follow-up study ‘150 Days of Gut Flora’, which aims to map out various microbiota compositions over a longer period of time. Once again, help from citizens is indispensable. Every sample counts.”

More info on www.vib.be/gutflora. To join the project, simply register at www.vlaamsdarmfloraproject.be.

Publication
Vandeputte et al., Nature 2017
Wilck et al., Nature 2017

Go back to the overview on 'Microbiology'

Front row from left to right: Gunter Kathagen, Gwen Falony and Doris Vandeputte
Back row from left to right: Kevin D’hoe, Sara Vieira-Silva and Jeroen Raes



Gut flora are sensitive to salt

The Nature issue that highlighted Quantitative Microbiome Profiling also included a publication from the ECRC Berlin, under  articipation of Markus Kleinewietfeld (VIB Center for Inflammation Research -UHasselt).

The study describes how salt reduces the number of specific gut commensals in mice. Markus: “We found that high salt intake depletes lactobacilli in mice and thereby indirectly affects immune cells that play a key role in autoimmune diseases and hypertension. Although these results offer potential for therapy development, more research is needed to unravel the complex interaction between nutrition, gut flora and immunity, and how all those factors impact diseases. This is just the start.”