Sunday, 6 January 2019

Modeling the microbiome


The gut microbiome -- the world of microbes that inhabit the human intestinal tract -- has captured the interest of scientists and clinicians for its critical role in health. However, parsing which of those microbes are responsible for effects on our wellbeing remains a mystery.

The human gut microbiome as yet is too diverse to fully analyze. Instead, the research team, led by Carnegie Institution for Science biologist Will Ludington, used the fruit fly as a model organism to tease apart how the presence of particular gut bacteria could lead to physical and behavioral effects in the host organism.
In their paper, "Microbiome interactions shape host fitness," Carlson, Jones, Ludington and colleagues examine the interactions between five core species of bacteria found in the fly gut, and calculate how the presence or absence of individual species influences aspects of the fly's fitness, including lifespan, fertility and development. "The classic way we think about bacterial species is in a black-and-white context as agents of disease -- either you have it or you don't," Ludington said. "Our work shows that isn't the case for the microbiome. The effects of a particular species depend on the context of which other species are also present."

Building on previous research that found the presence versus the absence of bacteria affected the longevity of an organism (sterile hosts lived longer), the researchers' work on this project revealed that the situation is far more nuanced. For example, the presence of certain bacteria might increase the host's fecundity, while others might decrease longevity. "As we examined the total of what we call a fly's fitness -- it's chances of surviving and creating offspring -- we found that there was a tradeoff between having a short lifespan with lots of offspring, versus having a long lifespan with few offspring," Ludington explained. "This tradeoff was mediated by microbiome interactions."


To decipher these interactions, Ludington performed a combinatorial assay, rearing 32 batches of flies each inhabited by a unique combination of the five bacteria. For each bacterial combination, Ludington measured the fly's development, fecundity and longevity. The analysis of the interactions required Carlson and Jones to develop new mathematical approaches.

What the study shows, the researchers said, is that the interactions between the bacterial populations are as significant to the host's overall fitness as their presence -- the microbiome's influence cannot be solely attributed to the presence or absence of individual species. "In a sense," said Jones, "the microbiome's influence on the host is more than the sum of its parts."

See:

Alison L. Gould, Vivian Zhang, Lisa Lamberti, Eric W. Jones, Benjamin Obadia, Nikolaos Korasidis, Alex Gavryushkin, Jean M. Carlson, Niko Beerenwinkel, William B. Ludington. Microbiome interactions shape host fitness. Proceedings of the National Academy of Sciences, 2018; 201809349 DOI: 10.1073/pnas.1809349115

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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