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Advances in the Human Genome Identify Gut Bacteria

Gut Bacteria

The role genetics and gut bacteria play in human health has long been a fruitful source of scientific inquiry. A new study published in Nature Microbiology marks a significant step forward in unraveling this complex relationship. Its findings could transform our understanding and treatment of all manner of common diseases, including obesity, irritable bowel syndrome, and Alzheimer’s disease.

The international study, led by the University of Bristol, found specific changes in DNA affected both the existence and amount of particular bacteria in the gut.

“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,” said lead author Dr David Hughes, Senior Research Associate in Applied Genetic Epidemiology.

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 bacteria, Bifidobacterium, that uses or digests lactose as an energy source.

This study, the biggest of its kind, identified 13 DNA changes related to changes in the presence or quantity of gut bacteria. Researchers at Bristol worked with Katholieke Universiteit Leuven and Christian-Albrecht University of Kiel to analyze 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 feces, also registered the presence and abundance of hundreds of gut bacteria.

“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,” said Dr Hughes.

Such investigations could hold the key to unlocking the intricate biological mechanisms behind some of the biggest health challenges of our time. “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,” said study co-author Dr Kaitlin Wade, Lecturer in Epidemiology at the University of Bristol. “The implications for our understanding of human health and our approach to medicine are far-reaching and potentially game changing.”

Conclusion/ Overall, this work marks a growing catalogue of genetic associations that will provide insight into the contribution of host genotype to gut microbiome. Despite this, the uncertain origin of association signals will likely complicate future work looking to dissect function or use associations for causal inference analysis.

Source: Hughes, D.A., Bacigalupe, R., Wang, J. et al. Genome-wide associations of human gut microbiome variation and implications for causal inference analyses. Nat Microbiol (2020). doi.org/10.1038/s41564-020-0743-8
Article from press statement provided by Nature Microbiology.

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