A study, published in the journal eLife, reveals that pathogenic shifts in the microbiome prevent tissue repair and regeneration. It links endogenous microbiota with the host immune responses, affecting an organism’s ability to heal itself. The researchers from the Stowers Institute for Medical Research conducted the respective study. The scientists showed that a dramatic shift in the microbial community of planaria robs its regenerative abilities. This similar shift has been examined in human inflammatory disorders as well.
Note that previous attempts of mimicking this effect in the lower organisms, like fruit flies or zebrafish, have been proven unsuccessful. However, this study serves as a valuable model in explaining the basic molecular mechanisms responsible for the interplay of immunity and regeneration. It can potentially be beneficial in heading toward new therapies for treating human ailments like chronic non-healing wounds.
According to the researchers changing in the nature of microbiome affects the way the immune system responds to the changes, plus it impacts the expected implementation of regenerative processes.
The immune system works in a two-way manner. First, it was believed to hinder the effective process of tissue regeneration and repair. However, recently it has been proven to promote this process as well. During this respect research, an unexpected problem in the laboratory presented an opportunity to unfold this puzzled duality of the immune system.
The planaria’s population, employed for the research, struck part of an infection. Large size lesions started to grow around their eyes which grew larger until the complete degeneration of the entire head. What actually surprised the researcher was the worms didn’t regenerate their head normally. The infection somehow spoilt their regenerative powers.
What did the research team do?
The researchers have developed a modified tank system that is capable of circulating and sanitizing the culture media for rearing the worms healthy. However, when taken out of the media, the worms quickly got sick again.
Amazingly, the researchers see that the planaria could successfully be treated for their tissue degeneration. That too with antibiotics which suggests that bacteria may play a part in it. For the determination of the planarian bacterial content, the researchers conducted a bacterial census.
They found the microbiome of the worms to be similar to that of humans. Healthy worms housed a large population of Bacteroides and a smaller population of Proteobacteria. The former is a group of helpful, kind, symbiotic bacteria. While the latter is a group containing a number of dangerous human pathogens that normally cause ulcers and cancers as well.
Upon developing the lesions, the worms experienced a huge upsurge in Proteobacteria. The researchers used an advanced molecular technique called RNA interference to test that if it was the bacteria or the immune system’s response to the bacteria that impaired the regenerative powers in the worms. They silenced the core components of the immune system and observed how each one affected the ability of the worms to repair their lesions and regenerate their heads during infection.
What do the findings suggest?
The findings of the research show that blocking TAK1 kinase makes the worms were able to recover from the damage. The research team looked at other genes, interacting with TAK1 kinase including activators and inhibitors. They found that most of them also affected regeneration during the infection.
The results suggest that there are genes that prompt degeneration in one case, and regeneration in another. Only when we block a pathway, we can allow regeneration to occur even in the presence of infection.
Our healthcare system struggles with bacteria, impeding healing in patients and ineffective antibiotics. This research helps to understand that the genes and pathways involved in the immune response. It may further interpret the signals, determining whether an organism decides it is beyond repair or tries to regenerate.