Wheeler Lab Postdoc Explores Gut Microbial Rhythms in Highlighted PRX Life Publication

Reposted from the University of Toronto's Department of Chemistry.

A postdoctoral fellow from the Wheeler Microfluidics Laboratory, which is located at the Donnelly Centre for Cellular and Biomolecular Research, has published research on the ebb and flow of bacteria in the human digestive system.

Dr. Ali Salari is one of two authors, along with Dr. Jonas Cremer of Stanford’s Department of Biology, of “Diurnal Variations in Digestion and Flow Drive Microbial Dynamics in the Gut,” which went live as a highlighted article in the journal PRX Life on June 9th.

The article explores the gut microbiome, a community of trillions of bacteria living in the human large intestine, which plays a role in nearly every aspect of human health. The gut microbiome has been linked to many diseases, from colon cancer to brain disorders.

“Unfortunately, lab experiments and animal studies provide only a limited view of how the many factors in our bodies affect these bacteria,” said Salari. 

To better understand this complex system, he and Cremer created a computer model using real data from past experiments. “The model allowed us to examine how bacteria grow and behave in the first part of the colon, known as the proximal colon. We focused on how the amount of food waste reaching this part of the intestine changes throughout the day and how that, in turn, affects bacterial population dynamics.”

One challenge in the process involved sifting through those past experiments, seeking experimental observations that could be used as input for the model.  “Validated data on the temporal dynamics of the cross-talk between the gut and its microbiota remain limited,” he noted.

Salari and Cremer began work on the model prior to Salari joining U of T, but potential exists for Wheeler Lab activities to take this research further. A pioneer in digital microfluidics for biomedical applications, including on-chip bacterial characterization, the lab offers key expertise that can be applied to explore further applications of Salari’s model. Such future work might leverage the group’s lab-on-a-chip technologies, for example. “It could allow us to recreate essential gut-like conditions, such as flow dynamics, nutrient gradients, and spatial organization, on a small, controllable scale.”

“By integrating these experimental platforms with our computational models, we can open new avenues to investigate microbial interactions and validate predictions under near-physiological conditions,” said Salari. “This combined approach can potentially bring us closer to replicating the true complexity of the in vivo gut environment and can provide a powerful framework for studying disease mechanisms in unprecedented detail.”

The model has already revealed much, finding that daily changes in the gut microbiome are largely influenced by when and how often a person eats. As the types and amounts of leftover nutrients from food vary over the course of the day, so do the populations of bacteria in the colon. Despite large daily fluctuations, the average number of bacteria remains fairly stable except when something goes wrong, such as in diseases like diarreah. 

“Our model offers new insight into how and why these bacterial populations rise and fall on a daily basis. It shows that several key factors, such as changes in food flow and nutrient availability, the natural movement of intestinal contents, and the special structure of the cecum (a pouch-like section at the start of the large intestine), all work together to produce these cycles.”

“The model suggests that our bodies may be more affected by these daily microbial cycles than we currently realize.”

For Salari, the cross-disciplinary nature of the work was another highlight of the project.  “Integrating biomedical engineering and mathematical modelling into the context of biology and biochemistry was an exciting experience,” Salari said. “It highlighted for me how deeply interconnected scientific disciplines have become.”

He is excited by the possibility of building on the work already accomplished.  "Future research can build on our findings by incorporating more aspects of human physiology and by exploring how different types of bacteria compete and interact. It will help create a more complete picture of how our gut truly works.”