Oliver Thewalt

    Oliver Thewalt

    Theoretical Physics | Quantum Biology | Dark Matter Research Cluster

    Host microbiota constantly control maturation and function of microglia in the CNS.

    http://www.ncbi.nlm.nih.gov/pubmed/26030851

    Abstract

    As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.

    Host microbiota constantly control maturation and function of microglia in the CNS.

    Uni Klinikum Freiburg 

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     Host microbiota control maturing and functioning of brain immune cells / Short-chain fatty acids function as messengers between the gut and the brain / Publication in Nature Neuroscience

    The gut's microbiome has an impact on the brain's immune response throughout life, with a possible effect on the course of diseases affecting the brain, such as Alzheimer's disease or multiple sclerosis. A neuropathological research team at the University Medical Center Freiburg has uncovered these effects in mice. The scientists have been able to demonstrate that the function of microglia, also called brain macrophages, is controlled by metabolites of gut bacteria. During the digestion of fibres, in particular, intestinal bacteria produce short-chain fatty acids necessary for proper microglia function. Mice whose intestines were free of bacteria developed immature and stunted microglia. When intestinal flora was reintroduced, microglia cell morphology and function recovered.

    This study highlights the importance of a balanced diet for the prevention of brain diseases and indicates that there may be a link between gut bacteria and the genesis of neurodegenerative diseases. These findings will be published in the July issue of the renowned journal Nature Neuroscience and already available as advance online publication.

    Microglia are also known as phagocytes of the brain, or brain macrophages. They eliminate invading pathogens and dead brain cells, thus contributing to the brain's life-long plasticity. Malfunctioning microglia cells play a role in a number of brain diseases. Until now, the maturing and activation of these cells has been unclear.

    Without gut bacteria, the brain's immune cells become stunted

    Prof. Dr. Marco Prinz, Medical Director at the Institute of Neuropathology at the University Medical Center Freiburg and associated member of the BIOSS Centre for Biological Signalling Studies Freiburg, heads the research group consisting of members from Freiburg, Rehovot (Israel), Munich, Mainz, Cologne and Berne (Switzerland). Together with the lead authors, Dr Daniel Erny and Anna Lena Hrabe de Angelis he has been able to demonstrate - using different mouse models - that a functioning immune system of the brain depends on healthy gut bacteria. The researchers examined animals that had been raised and kept in a completely sterile environment. The animals' microglia were stunted and immature, and hardly responded to the brain's inflammatory signals. "Our results indicate a constant flow of information between gut bacteria and brain macrophages," so Prof. Prinz. Animals whose intestinal bacteria had been eliminated by a four-week course of antibiotics also showed an impaired immune response. When put into contact with animals harbouring a normal gut flora, the previously sterile animals quickly developed their own intestinal flora, which had a positive effect on their immune response. According to the neuropathologist, the general outcome was that "the more diverse the gut bacteria, the better developed were the microglia."

    Fermented fibre controls the brain's immune response

    The researchers showed that short-chain fatty acids function as signal between the intestinal flora and the microglia in the brain. Short-chain fatty acids are a product of the bacterial fermentation of fibres, dairy products and other foods. They can travel to the brain via the bloodstream, where they help microglia cells to quickly and efficiently fight any inflammatory reactions. "Our findings show just how important a balanced diet, contributing to bacterial production of short-chained fatty acids, is for mental health," says Prof. Prinz.

    Does intestinal flora also have an effect on Alzheimer's, Parkinson's and multiple sclerosis?

    The study may well be very relevant for humans. "Our study results are in line with previous clinical studies and investigations by other research groups," explains Prof. Prinz. Autoimmune disorders of the intestines, such as Crohn's disease, have been linked with a lack of short-chained fatty acids. There have been investigations into treatment by stool transplantation, meaning that the intestinal flora is transferred from one person to another. How strong the effect of the gut microbiome on the functioning and development of the human brain actually is, remains to be investigated.

    Host microbiota keep the brain healthy

    Darmbakterien sorgen für gesundes Gehirn



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