The human digestive tract is home to billions of microorganisms, and scientists think that these organisms play a significant role in human health. Exactly what role they play is still a mystery. Researchers at the Buck Institute studied worms to infer how bacteria can influence its host.
Scientists previously thought gut bacteria secretions were responsible for immune-boosting properties in human gastrointestinal tract. However, there is a new indication that it is the bacteria’s genome that does all the work. Oddly enough, this discovery did not come from the study of a human subject, but that of the nematode worm C. Elegans.
Bacteria are a worm’s primary food source, and the study reveals how different genes in bacteria modify the biology of the worms that eat them. According to Professor Pankaj Kapahi of the Buck Institute, “We have uncovered the effects of bacterial genetics on the physiology of a simple organism, which may serve as a model system to study the gut microbiome in mammals to identify novel therapeutics to treat diseases.”
The basis of the study began as a way to understand why worms that ate less lived longer. Now, the goal has shifted to understanding how the bacteria that the worms eat communicate with the host via genetic markers.
Study of the Gut Bacteria Mutant Genomes
The research team used genetically mutated bacterial strains to observe any changes in their nematode subjects. When worms are subjected to life-threatening environmental conditions, they enter a state known as Dauer, where larvae shut down their functions and enter a sort of morphological stasis. It has long been known that dauer is triggered by compounds produced in the bacteria that worms eat and that the pathway used to signal the response is similar to insulin-like signaling.
If the worm entered Dauer, the team would know if the mutations in bacteria affected them. Using 4,000 different strains of e-Coli bacteria, the team found 56 mutant strains that enhanced dauer formation. This showed the team whether or not the genes in bacteria that are normally present at low levels in the human G.I. microbiome would affect the insulin-like signaling pathway in worms.Using 4,000 different strains of e-Coli bacteria, the team found 56 mutant strains that enhanced dauer formation.Click To Tweet
One bacterial mutant, adenylate cyclase (cyaA), was shown to modulate dauer formation and increase lifespan by influencing TGF-β signaling. What’s more, they uncovered the entire molecular mechanism that allowed the sensory neurons to communicate with the target cells to allow the worm to enter dauer.
These results show us that the combination of bacterial and worm genetics can be useful tools to study how gut bacteria modulate nutrient signaling and host physiological processes such as growth and aging. Often, these processes are similar in higher organisms, so C. Elegans may give scientists a map that will get them closer to understanding how gut bacteria affect the human body.
Worms make good test subjects for these types of experiments because it only takes 10 to 15 days to get results, meaning that this study may have far-reaching consequences in our growing understanding of the human gastrointestinal system.