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Can the intestinal flora be modeled for protection against infection?
The importance of the intestinal flora (microbiome) for the immune system has already been proven by numerous studies. Conversely, the question arises of how the intestinal flora can be designed so that it offers the most extensive protection against infection. For this, however, the protective effect of individual bacterial strains must first be decrypted, which could be done with the help of a new model.
Scientists from the Ludwig Maximillians University (LMU) in Munich, the Technical University of Munich and the University of Vienna have established a mixture of only 15 bacteria in the mouse model that protects just as well against Salmonella as the natural intestinal flora. Based on the model, the interactions of the intestinal flora with hosts and pathogens can be specifically investigated for the first time, according to the LMU. The researchers published their results in the journal "Nature Microbiology".
Healthy intestinal flora offers good protection against infection
The multitude of microorganisms in our gut form a complex community. "This natural intestinal flora provides very efficient protection against infections, for example with Salmonella or with Clostridium difficile, the causative agent of antibiotic-associated diarrhea," reports the LMU. The research team led by LMU biologist Prof. Bärbel Stecher has now "successfully established a consortium - a bacterial community - of only 15 types of bacteria in the mouse model that offers the same protection against infections as the diverse natural gut microbiota."
Interaction of the intestinal flora with the host and pathogens
According to the researchers, the new model will enable targeted studies on the interaction of the gut microbiota with hosts and pathogens in the future. In the long term, this could also enable the development of new therapies, reports the LMU. If, for example, the protective effect of individual bacteria could be determined, the intestinal flora could also be modeled under certain circumstances to avoid infections.
Which bacteria protect against infection?
The technical term for the protective mechanism of the intestinal flora against pathogens is “colonization resistance”. Changes in the intestinal flora, such as those caused by taking antibiotics, can abolish this resistance to colonization, the scientists explain. However, “so far it remains unclear what role individual types of bacteria play in colonization resistance,” says Prof. Bärbel Stecher. The new model should help here in the future.
Germ-free mice colonized with artificial intestinal flora
To decipher the functions of the gut microbiota, the researchers first identified "a minimal consortium of 12 types of bacteria" that are representative of the mouse. This consortium, known as Oligo-MM-12, was used to colonize germ-free mice, but the artificial intestinal flora did not offer the same protection against Salmonella as the natural microbiome. The scientists therefore looked for a new approach to identify the missing bacteria. For this they used the so-called "genome-guided microbiota design".
Optional anaerobic bacteria with special importance
"We compared the genetic information of the Oligo-MM-12 with that of normal complex microbiota and identified the gene groups that are missing in the consortium," explains Prof. Stecher. Above all, there were no characteristic genes for so-called "facultative anaerobic bacteria". This special group of bacteria can grow optimally in the presence of oxygen, but can also thrive without oxygen. For their part, Salmonella are also facultative anaerobic, the researchers report. In contrast, the bacteria in the Oligo-MM-12 consortium were predominantly obligate anaerobes for which oxygen is toxic.
Protection against Salmonella comparable to the natural intestinal flora
In the next step, the researchers therefore "added three facultative anaerobic bacterial species found in the mouse intestine" and subsequently demonstrated experimentally that "only in this combination is colonization resistance to Salmonellae comparable to that of mice with a naturally complex microbiota", reports Prof. Stecher.
Functions of the intestinal flora decipherable?
According to the scientists, the identified consortium and the new principle of "genome-guided microbiota design" can make a decisive contribution to uncovering important previously unknown functions of the gut microbiota. Bacterial groups that are suitable for the treatment of disease-related malfunction of the intestinal microbiota can also possibly be determined, the researchers write. (fp)