Fibre is a valuable part of a healthy diet. The largely indigestible foodstuffs are a feast for intestinal bacteria, which produce short-chained fatty acids from them. These short-chained fatty acids have a positive effect on inflammatory diseases such as rheumatoid arthritis. If arthritis patients eat a fibre-rich diet this leads to an increase in the number of regulatory t-cells which combat autoimmune reactions, in other words reactions in which the body's immune system attacks the organism itself. Researchers at FAU have also discovered that patients experience an improvement in their general sense of well-being if they have a fibre-rich diet. The researchers have published their findings in the journal Nutrients.
Intestinal bacteria play a considerable role in triggering autoimmune diseases. These microorganisms, which account for roughly two kilos of an adult's bodyweight, have to feed well in order to keep the intestinal flora intact. In other words, they need fibre. The modern diet, however, tends to be rather low in fibre, which can lead to an imbalance in the intestinal flora An imbalance in intestinal microbiota has been linked to autoimmune disease. Under these circumstances, the microorganisms produce fewer fatty acids. These fatty acids, including propionate and butyrate, are found in joint fluid, contribute to keeping joints working and prevent inflammation.
Another study conducted by the team led by Prof. Dr. Mario Zaiss, Professorship of Immune Tolerance and Autoimmunity, supports these results. The FAU researchers investigated how to lower levels of the protein zonulin in the intestine, a known trigger of autoimmune diseases. One of their findings was that nutrition and intestinal bacteria can affect zonulin production. The results of this study were published in the journal Nature Communications.
Prof. Dr. Mario Zaiss, Professorship of Immune Tolerance and Autoimmunity. (Image: private)
The progression from an asymptomatic state to the onset of the disease
In the zonulin study, the FAU team led by Prof. Dr. Mario Zaiss investigated to what extent intestinal microbiota contribute to the progression from asymptomatic autoimmunity to the onset of the disease. The researchers discovered that the intestinal epithelial barrier, the protective coating of the intestines, produced more zonulin whenever there was an imbalance in gut bacteria. Zonulin acts to make proteins which seal the gaps between cells in the intestinal barrier known as tight junctions permeable for specific substances such as peptides or fragments of bacteria. As the bacterial fragments are similar to components in the human body, the FAU researchers suspect that the organism cannot differentiate between the foreign substances and the body's own parts. The organism attacks invaders and creates antibodies which attack the body's own cells at the same time. The result is autoimmune inflammatory reactions, triggering the onset of disease in rheumatoid arthritis.
The study found that an increased concentration of zonulin in the intestines of previously asymptomatic patients with autoimmunity led to an increased risk of developing arthritis within the following year. By taking biopsies of the lining of the small intestine, the FAU researchers were able to demonstrate that the tight junctions, the intestinal barrier, changed and became more permeable when zonulin levels were high. When the intestines became more permeable for lactulose, this indicated the onset of active arthritis in both mice and people.
Less zonulin, fewer complaints
As the researchers were already aware of the positive effects of the short-chained fatty acid butyrate on rheumatoid arthritis on the basis of their previous study, they gave mice butyrate during the zonulin study. The results indicated that this treatment delayed the onset of arthritis, lowered the concentration of zonulin and strengthened the intestinal barrier. The effect was intensified when they also gave larazotide acetate, a substance which has already been used in clinical studies to treat celiac disease, or gluten intolerance. When larazotide acetate, which is known to reduce zonulin production, was given, the inflammatory processes in the joints decreased, bone density increased and the onset of arthritis was delayed.
The FAU researchers believe that blocking zonulin production using larazotide acetate could also lead to a reduction in disease activity in the case of arthritis in humans. As the substance is already being tested in phase III studies, it may soon be able to be used for rheumatoid arthritis under certain circumstances.
Achieving intestinal balance with a fibre-rich diet
In addition, the FAU team recommends eating a fibre-rich diet to restore the balance of intestinal microbiota, thereby enabling intestinal microbiota to produce greater quantities of butyrate and strengthen the intestinal barrier. According to the researchers, eating a high-fibre diet can help to treat rheumatoid arthritis and possibly other autoimmune diseases as well. Prof. Dr. Mario Zaiss, who led the study, says 'Even Hippocrates recognised the importance of nutrition for health, believing that eating the wrong foods was one of the main reasons for illness: 'Let food be thy medicine and let medicine be thy food.' If illness can be triggered by eating the wrong foods, then this is all the more reason to investigate this issue carefully and carry out further research into the various connections.'
