'Game changing' research discovers 'striking' links between genes and gut bacteria
Recent population-based and clinical studies have identified a range of factors associated with human gut microbiome variation. Murine quantitative trait loci, human twin studies and microbiome genome-wide association studies have provided evidence that genes contribute to microbiome composition. But there is still poor overlap in genetic association across human studies.
The current international study, led by the University of Bristol and published in Nature Microbiology, found specific changes in DNA affected both the existence and amount of particular bacteria in the gut.
Lead author Dr David Hughes, senior research associate in applied genetic epidemiology, said: "Our findings represent a significant breakthrough in understanding how genetic variation affects gut bacteria. Moreover, it marks major progress in our ability to know whether changes in our gut bacteria actually cause, or are a consequence of, human disease."
Previous research has identified numerous genetic changes apparently related to bacterial composition in the gut, but only one such association has been observed consistently. This example involves a well-known single mutation that changes whether someone can digest the sugar (lactose) in fresh milk. The same genetic variation also predicts the prevalence of Bifidobacterium bacteria, that uses or digests lactose as an energy source.
This study identified 13 DNA changes related to changes in the presence or quantity of gut bacteria. Researchers at Bristol worked with Katholieke Universiteit Leuven, Belgium, and Christian-Albrecht University of Kiel, Germany, to analyse data from 3,890 individuals from three different population studies: one in Belgium (the Flemish Gut Flora Project) and two in Germany (Food Chain Plus and PopGen).
In each individual, the researchers measured millions of known DNA changes and, by sampling their faeces, also registered the presence and abundance of hundreds of gut bacteria.
They found 'striking' and 'compelling' correlations between gut bacteria and genes across the populations.
Dr Hughes said: "It was exciting to identify new and robust signals across the three study populations, which makes the correlation of genetic variation and gut bacteria much more striking and compelling. Now comes the great challenge of confirming our observations with other studies and dissecting how exactly these DNA changes might impact bacterial composition."
Study co-author Dr Kaitlin Wade, Lecturer in Epidemiology at the University of Bristol, said added that such investigations could hold the key to unlocking the intricate biological mechanisms behind some of the biggest health challenges of today.
"A strength here is that these findings provide a groundwork for causal analyses to determine, for instance, whether the presence of specific bacteria increases the risk of a disease or is a manifestation of it."
"The implications for our understanding of human health and our approach to medicine are far-reaching and potentially game changing."
Source: Nature Microbiology
Hughes. D.A., Bacigalupe. R., et al
"Genome-wide associations of human gut microbiome variation and implications for causal inference analyses"
