Summary: Researchers have developed a new mathematical model that analyzes the interactions between gut bacteria.
Source: UC Santa Barbara.
The gut microbiome — the community of microbes living in the human intestinal tract — plays a crucial role in health, but identifying which microbes drive specific effects remains challenging.
To advance this understanding, physicists Eric Jones and Jean Carlson at UC Santa Barbara have developed a mathematical framework to analyze how gut bacteria interact and jointly influence host traits. Using the fruit fly (Drosophila melanogaster) as a controlled model system, their approach teases apart how combinations of bacterial species shape host development, reproduction, and lifespan. The team’s results appear in the Proceedings of the National Academy of Sciences.
“Over the past two decades, research has shown that the microbiome interacts with the immune system, the nervous system and many other aspects of host physiology,” said Jones, a graduate student researcher in Carlson’s lab. “Numerous diseases correlate with particular gut microbial compositions, but determining causal links and interaction effects is difficult in complex human microbiomes.”
Because the human gut microbiome includes thousands of species and complex interactions, the team studied a simpler, natural microbiome: five core bacterial species commonly found in the fruit fly gut. Led by Carnegie Institution for Science biologist William B. Ludington, the experimental design allowed the group to measure how each possible combination of these five bacteria affected fly fitness. That combinatorial approach enabled precise measurement of how individual species and their interactions influence host outcomes.
In the study, “Microbiome interactions shape host fitness,” the researchers raised germ-free flies and then colonized those flies with every possible combination of the five bacterial species, producing 32 distinct microbiome communities. For each community, they quantified bacterial abundances and measured fly traits including development time, fecundity (reproductive output) and lifespan. These data provided the basis for new mathematical analyses that adapt concepts from genetic epistasis to quantify microbial interaction effects on host fitness.
“A common starting point is to consider only pairwise interactions between bacterial species,” said Carlson, whose work applies physics to complex biological systems. “Our analysis shows that pairwise models often miss important higher-order interactions: the effect of three or more species together can differ substantially from what pairwise combinations predict.”
The findings reveal that interactions among microbial species can be as important as the presence of individual species in determining host fitness. For some traits, such as development rate and fecundity, increased bacterial diversity tended to converge on similar outcomes and showed limited dependence on interactions. In contrast, host lifespan and the resulting bacterial community abundances were strongly shaped by interactions, including many higher-order effects that involve three, four, or all five species.
These higher-order interactions were context-dependent: the same bacterial species could have different effects on the host depending on which other microbes were present. That context dependence produced life-history tradeoffs in the flies. For example, certain microbiome configurations accelerated reproduction but were associated with shorter lifespan, while other configurations supported longer-lived flies with lower reproductive output. “We observed a tradeoff between short lifespan with high fecundity and long lifespan with low fecundity, and this tradeoff was mediated by microbiome interactions,” Ludington explained.
To quantify these patterns, Jones and Carlson extended mathematical tools originally developed for genetic epistasis to capture microbial interactions across multiple species. Their model allowed them to partition the contributions of single species, pairwise interactions and higher-order interactions to each measured trait. Depending on the trait, higher-order interactions accounted for 13–44% of cases where interactions mattered, and many interaction terms influenced multiple traits, reflecting the interconnected nature of life-history outcomes.
These results underscore that microbiome effects on hosts are often “more than the sum of their parts.” Understanding the population dynamics and interaction structure of gut communities may clarify how shifts in native microbiota can permit the overgrowth of opportunistic pathogens or contribute to disease. “Many infections arise from bacteria already present in the host that are normally controlled by native gut communities,” Carlson said. “Disease can reflect changes in those community dynamics rather than the introduction of a novel organism.”
The modeling framework and experimental design demonstrated in flies provide a tractable path for studying microbiome interactions more broadly. While the human gut microbiome is far more complex, the mathematical approach can be scaled and adapted to infer interaction networks among larger numbers of species, potentially illuminating links between microbiome composition and conditions ranging from autoimmune disorders to neurological and mood-related illnesses.
Additional contributors to the study include Alison Gould, Vivian Zhang and Benjamin Obadia of UC Berkeley; Lisa Lamberti, Nikolaos Korasidis and Niko Beerenwinkel of ETH Zurich; and Alex Gavryushkin of the University of Otago.
Source: Sonia Fernandez, UC Santa Barbara
Publisher: NeuroscienceNews.com (organized by the publisher)
Original Research: “Microbiome interactions shape host fitness,” Alison L. Gould et al., Proceedings of the National Academy of Sciences. Published November 1, 2018. doi: 10.1073/pnas.1809349115
Microbiome interactions shape host fitness
Gut bacteria influence host development, fecundity and lifespan, while the host environment also shapes microbial community structure. To dissect how individual species and their interactions affect host fitness, the authors created germ-free Drosophila and colonized flies with every possible combination of five core gut bacterial species. They measured community abundances and fitness traits, finding that higher bacterial diversity generally accelerated development and reproduction but shortened lifespan, revealing a fecundity–longevity tradeoff. Using adapted mathematical methods from genetic epistasis, the study shows that development and fecundity depend less on interactions, whereas lifespan and microbial abundances are highly influenced by pairwise and higher-order interactions. Context-dependent interactions often match the magnitude of single-species effects, indicating that microbiome interactions can be as important as individual species in shaping host outcomes.