Researchers working at Paris Cité University, INSERM, CNRS and Assistance Publique-Hôpitaux de Paris, in France, have published an article this week in Science Translational Medicine describing how dysregulation of  gut-flora bacteria plays a direct role in the development of human autoimmune disease. Lead authors, Prof. R. Monteiro and Dr. J. Gleeson, carried out the work at Centre de Recherche sur l’Inflammation at Bichat Hospital campus.

The researchers focused on an autoimmune disease affecting kidneys, called IgA nephropathy. This condition is diagnosed in about 1/100,000 people every year in Ireland, and most commonly affects men between the age of 20-40 years. It is a leading cause of kidney failure worldwide, and can be suspected early-on by doing a simple urine test.

Analysis of the gut-flora in samples from patients with IgA nephropathy showed an excess of bacteria that are capable of degrading glycans, or sugar-chains, attached to human proteins. These bacteria were shown to modify specific glycans attached to a molecule called IgA1, which is secreted into the gut. After being modified by these bacteria in the gut, this human molecule then returned to the blood stream where it was no longer recognisable as being part of “self”, and so was attacked by the patients’ own immune system. Trapping of the resulting immune-complexes in kidneys led to the development of kidney disease. In addition to results obtained with human samples, this process was demonstrated in more detail using mice.

The main culprit species that was found increased in patients with IgA nephropathy is called Akkermansia muciniphila, which is being sold online for the treatment of obesity and metabolic disease. While it was shown that A. muciniphila needed to be alive to induce IgA nephropathy, the findings highlight the importance of a safe, balanced approach to gut health.

Treatments targeting the immune-system lining the gut have already been developed for IgA nephropathy. These findings will now inform attempts to develop other possible treatments directly targeting the gut-flora, which do not currently exist for IgA nephropathy.

The study describes a new mechanism of human disease whereby the gut-flora induces changes in human molecules, causing them to be targeted by the patient’s own immune system. According to the authors, this  “allows for a shift in the understanding of acquired autoimmunity”.