The human gut is home to trillions of microbes, and even bacteria of the same species can look and behave very differently. A team led by researchers at the University of Würzburg has uncovered how one common gut bacterium, Bacteroides thetaiotaomicron, changes its shape depending on where it lives and what it’s doing.

Researchers noticed that B. thetaiotaomicron cells could vary in size, both in lab conditions and when isolated from different parts of the gut. To investigate the cause, they developed a highly sensitive RNA sequencing method that allowed them to study the gene activity of individual sub-populations based on their size. This sensitive RNA-seq method enabled the team to dissect gene expression differences even in tiny, morphologically distinct bacterial populations, revealing how metabolic specialization underlies their size variation. This technique can be broadly applied to study phenotypic heterogeneity in other microbial communities where sample amounts are limited.

The researchers also identified key genes whose expression levels matched the size of the bacteria. By deleting or overexpressing these genes, they confirmed that they play a direct role in controlling cell size. These findings suggest that shape-shifting might be a built-in strategy that helps bacteria adapt and survive in changing environments. It also highlights how RNA sequencing can reveal hidden layers of complexity in even the smallest life forms.