Scientists found mechanism to promote the growth of good bacteria in human gut

A novel mechanism by which "good" bacteria colonize the gut, which could lead to new probiotic therapies.


Gut bacteria are essential for human health, yet there is insufficient knowledge about the factors and mechanisms that make beneficial bacteria successful colonizers. One of the most prevalent bacterial species in the human gut is Bacteroides thetaiotaomicron, which is frequently present in lean, healthy people. Clinical trials are currently being conducted to treat numerous diseases by modifying the gut microbiota.

Yale researchers found a novel mechanism for beneficial gut bacteria colonization. Bacteroides thetaiotaomicron responded to carbon deficiency by sequestering a portion of the molecules for an essential transcription factor within a membrane-less compartment.

The team established that Sequestration of the transcription factor increased its activity, which modified the expression of hundreds of bacterial genes, including several that promote gut colonization and control central metabolic pathways in the bacterium. These findings reveal that “good” bacteria use the Sequestration of molecules into membrane-less compartments as a vital strategy to colonize the mammalian gut.

Aimilia Krypotou, a postdoctoral fellow in Groisman’s lab and lead author of the study from yale university, said, “One of the things that emerged is that when an organism is starved for carbon, that is the signal that helps produce properties that are good for surviving in the gut.”

Krypotou hypothesized that the different regions would confer a new biophysical feature to the transcription factor essential for bacteria to survive in the gut. She successfully tested the theory in a series of studies.

She said, “Most studies just look at an abundance of the bacterium. If we don’t understand what’s happening at the molecular level, we don’t know if it would help.”

Groisman said, “Krypotou’s key insight was to deduce novel properties for the bacterial transcription factor — termed Rho — based on the extra region. Sequestration of the transcription factor takes place by a process known as liquid-liquid phase separation, a ubiquitous phenomenon present in a wide variety of cells including those of humans.”

Groisman said, “This phenomenon has been known but is usually associated with stress in eukaryotic organisms, such as plants, animals, and fungi. Recently it was realized it could also happen with bacteria. In our case, we established that it occurs in commensal gut bacteria, which require it for survival in the gut. One could conceivably imagine that if one were to manipulate organisms prone to this effect, perhaps one could improve organisms beneficial to humans.”

He could predict novel features for the bacterial transcription factor Rho based on the different areas. The transcription factor is sequestered through a mechanism known as liquid-liquid phase separation, found in a wide range of cells, including human cells.

This newly discovered mechanism through which “good” bacteria colonize the gut could help spur the development of new probiotic therapies for gut health.

By triggering the sequestration of Rho molecules within a membrane-less compartment, carbon starvation and the murine gut increase Rho termination activity, thereby changing the expression of numerous genes. The results also highlight how a single, acquired domain within a highly conserved protein expanded its properties without changing its core biochemical function and now plays a critical role in the organism’s physiology.

Journal Reference:

  1. Emilia Krypotou, Xiaohui Gao, et al. Bacteria require phase separation for fitness in the mammalian gut. Science. DOI: 10.1126/science.abn7229
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