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Intestinal microbiota How does the intestinal flora protect us humans from infections?
The function of the intestinal flora has long been underestimated and only in recent years, the importance of the intestinal microbiota in the defense against pathogens again moved more into the focus of science. Researchers at the Helmholtz Center for Infection Research (HZI), together with experts from Yale University (USA), the Hannover Medical School (MHH) and the TWINCORE Center, have now investigated the relationship between various compositions of the intestinal flora and susceptibility to Salmonella infections.
The interactions between gut microbiota, immune system and pathogens have remained largely unexplored so far. In the mouse models, the scientists were now able to discover basic mechanisms of the intestinal flora in the defense against Salmonella. The composition of the intestinal flora therefore has a considerable influence on the sensitivity to Salmonella infections. The researchers have published their findings in the journal "Cell Host & Microbe".
The composition of the intestinal flora has a significant influence on the susceptibility to Salmonella infections. (Image: Alex / fotolia.com) Billions of microorganisms colonize our body
The human body is colonized by billions of microorganisms, with the composition of the so-called microbiota, the totality of the microorganisms that colonize humans' intestines, varying widely between individuals. According to the researchers, "In addition to genetic factors, environmental factors - such as nutrition - are reasons for this diversity." The different composition of the microbiota has also been linked for some years to the different sensitivities of humans to intestinal infections.
Significant influence on the risk of bowel disease
"The microbiota has become an increasingly important aspect of the research of intestinal diseases in recent years," emphasizes Dr. med. Till Strowig, Head of the HZI Junior Research Group Microbial Immunoregulation. Thus, pathogens would be combated in several ways. On the one hand, the microbiota is competing with the pathogens for nutrients and thus prevents the colonization of the host, on the other hand, the protection against pathogens can also be done indirectly via the initiation of a protective immune response of the host.
Sensitivity to salmonella infection was investigated
In the current study, the scientists have now addressed the question "to what extent the microbiome influences the protection against infection with Salmonella." They infected genetically identical mouse lines, which differed only in the composition of the microbiota, with Salmonella and documented the course the infection, the weight loss as well as the survival rate of the mice. At the end of the experiments, the researchers were able to determine the most sensitive mouse line as well as the most resistant mouse line. In this way, the experts have succeeded in identifying the bacteria of the microbiota, which are involved in the protection against Salmonella infection, according to the statement of the HZI.
Protective bacteria identified
Using state-of-the-art high-throughput sequencing methods, the scientists studied the exact differences in the microbial communities of the mouse lines, noting that in particular the number of certain bacterial families (Prevotallaceae and Verrucomicrobiaceae) was significantly higher in the resistant mouse line than in the sensitive mouse line. Based on this finding, some of these bacterial strains had been transplanted into susceptible mice. "The mice then showed a significantly increased protection against Salmonella," reports the HIZ. The experiment confirms that "the bacterial composition of the gut microbiota plays an important role in the protection against Salmonella infections", Dr. Strowig. In addition, it was successful to identify the protective bacteria families.
Production of cytokine interferon-gamma is increased
The scientists were also able to decipher how the protective mechanism works by the bacteria. Previous studies have already reported that in the immune response to Salmonella, the antimicrobials and cytokines (proteins that affect the growth and function of target cells) are formed at an early stage of the immune response. In the current experiments, an increased production of cytokine interferon-gamma (IFNγ) was found in the mice in the presence of the protective bacterial families. This protein plays a critical role in the initiation of immune responses to bacterial pathogens. When IFNγ production in the animals was switched off, increased protection could not be produced even with the addition of the protective bacterial cocktail, according to Strowig.
Protection also in the intestinal mucosa
Surprisingly, the Salmonella were not only fought in the intestinal interior, but in the investigated case, the body also repelled the pathogens in the tissue of the intestinal mucosa, in which Salmonella must penetrate the infection, the scientists report. The biggest surprise in the current study results is not "that there is a connection between the composition of the gut microbiota and the course of the disease, but the mechanism behind it," Dr. Strowig. In further studies, it would now be necessary to find out which of the two types of immune cells (T cells or innate lymphocytes) is more important for the immune system response of the intestinal mucosa. (Fp)