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19 Feb 2019

Balancing the gut – how the immune system maintains a healthy gut microbiota

An international team of researchers have uncovered a critical mechanism that establishes the balance between immune system and microbiome.

The researchers, under the lead of Christian-Albrechts-Universität zu Kiel Professor Alexander Scheffold, University of Melbourne Professor Axel Kallies, Laboratory Head at the Doherty Institute and Honorary at Walter and Eliza Hall Institute of Medical Research, Melbourne, and Dr Sascha Rutz from Genetech, San Francisco, studied molecular regulators of immune - microbiome interactions in mice concentrating on so called ‘regulatory T cells’, a cell type that plays an essential role in this system.

Humans live with countless bacteria, fungi and viruses which inhabit the surface areas of our bodies such as the gut, lung or skin.

These microbes, collectively are referred to as microbiome, fulfil critical functions in maintaining our health by preventing infections or helping to break down our food.

Our live with microbes is finely balanced by the immune system, which usually prevents microbes of taking hold of our bodies but ignores the beneficial microbiome.

Breakdown of this balance is associated with severe diseases such as inflammatory bowel diseases, skin diseases, allergies, obesity and autoimmune.

A central question in medical research is as to how our body maintains its beneficial coexistence with countless beneficial microbes while being ready to fight infections with their disease-causing counterparts.

In the study published today in Nature Immunology, researchers identified a molecule, c-Maf, that was critical for the development of regulatory T cells specifically in the gut environment and prevented the immune system from attacking our microbiome.

Loss of c-Maf in regulatory T cells resulted in hyperactivation of the gut’s immune system and in a substantially altered microbiome.

Further research showed that - once established - this altered microbiome was remarkably stable and could even be transferred to healthy mice, which then also developed an overshooting immune reaction in the gut despite having intact c-Maf dependent regulatory T cells.

These results show that both the immune system and the microbiota in a reciprocal manner contribute to establishing a fine balance in the gut which is essential to maintain a beneficial microbiome and keep the immune responses in check.

These results show how microbial imbalance contributes to chronic inflammatory bowel disease and highlights the need to re-establish a healthy microbiome to support lasting cure.