[{"command":"openDialog","selector":"#drupal-modal","settings":null,"data":"\u003Cdiv id=\u0022republish_modal_form\u0022\u003E\u003Cform class=\u0022modal-form-example-modal-form ecl-form\u0022 data-drupal-selector=\u0022modal-form-example-modal-form\u0022 action=\u0022\/en\/article\/modal\/7363\u0022 method=\u0022post\u0022 id=\u0022modal-form-example-modal-form\u0022 accept-charset=\u0022UTF-8\u0022\u003E\u003Cp\u003EHorizon articles can be republished for free under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence.\u003C\/p\u003E\n \u003Cp\u003EYou must give appropriate credit. We ask you to do this by:\u003Cbr \/\u003E\n 1) Using the original journalist\u0027s byline\u003Cbr \/\u003E\n 2) Linking back to our original story\u003Cbr \/\u003E\n 3) Using the following text in the footer: This article was originally published in \u003Ca href=\u0027#\u0027\u003EHorizon, the EU Research and Innovation magazine\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003ESee our full republication guidelines \u003Ca href=\u0027\/horizon-magazine\/republish-our-stories\u0027\u003Ehere\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003EHTML for this article, including the attribution and page view counter, is below:\u003C\/p\u003E\u003Cdiv class=\u0022js-form-item form-item js-form-type-textarea form-item-body-content js-form-item-body-content ecl-form-group ecl-form-group--text-area form-no-label ecl-u-mv-m\u0022\u003E\n \n\u003Cdiv\u003E\n \u003Ctextarea data-drupal-selector=\u0022edit-body-content\u0022 aria-describedby=\u0022edit-body-content--description\u0022 id=\u0022edit-body-content\u0022 name=\u0022body_content\u0022 rows=\u00225\u0022 cols=\u002260\u0022 class=\u0022form-textarea ecl-text-area\u0022\u003E\u003Ch2\u003EWhy gut bacteria are becoming key suspects in autoimmune diseases\u003C\/h2\u003E\u003Cp\u003EWhat causes the immune system to err in this way is not clear, but a growing body of research is looking at the trillions of microbes that share our bodies, known collectively as the microbiome, for an answer.\u003C\/p\u003E\u003Cp\u003EStudies of twins indicate that lifestyle, or environmental, factors can play a large role in autoimmune diseases.\u003C\/p\u003E\u003Cp\u003E\u2018If you just look at the concordance rate in twins (where both twins show the same trait), for instance for MS, it\u2019s only about 30% which is inherited. So the rest must be environment,\u2019 said Professor Markus Kleinewietfeld from the VIB Institute in Belgium.\u003C\/p\u003E\u003Cp\u003EMany different environmental factors are suspected of affecting the risk of autoimmune conditions, including diet.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ESalt\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3746493\/\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003EPrevious research\u003C\/a\u003E by Prof. Kleinewietfeld and others have found that high-salt diets can affect our immune systems, including cells responsible for inflammation. Inflammation is an integral part of the defence against infection, however it can cause tissue and organ damage when sustained at high levels.\u003C\/p\u003E\u003Cp\u003EThe immune system is balanced carefully between cells that promote inflammation and the cells that regulate them. Prof. Kleinewietfeld suspected that diet might disrupt this balance, at least partly, both directly by impacting different immune cells and indirectly by altering the gut microbiome.\u003C\/p\u003E\u003Cp\u003E\u2018We wanted to analyse how specific dietary factors could impact the gut microbiome and could relate to shifts in the immune system,\u2019 said Prof. Kleinewietfeld, who led the \u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/id\/640116\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003EENVIROIMMUNE\u003C\/a\u003E project to investigate the effects of salt.\u003C\/p\u003E\u003Cp\u003E\u2018What we actually found, which was quite surprising, was that (the high-salt diet) depletes specifically beneficial microbes, like lactobacilli, in the gut.\u2019\u003C\/p\u003E\u003Cp\u003ELactobacilli are a common type of \u2018friendly\u2019 bacteria found in the gut. There are many lactobacillus species, including some used in the commercial production of yoghurt, cheeses and sauerkraut.\u003C\/p\u003E\u003Cp\u003E\u2018We also did a little pilot study in humans, and that was also quite stunning because we could observe a depletion (of lactobacilli),\u2019 said Prof. Kleinewietfeld.\u003C\/p\u003E\u003Cp\u003EWithin just a few days, the researchers could \u003Ca href=\u0022https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6070150\/\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003Esee differences\u003C\/a\u003E in the people eating an extra six grams of salt a day. They not only had higher blood pressure, but more pro-inflammatory immune cells and fewer lactobacilli.\u003C\/p\u003E\u003Cp\u003E\u003Cfigure role=\u0022group\u0022 class=\u0022@alignleft@\u0022\u003E\n\u003Cimg alt=\u0022A smaller amount of lactobacilli in the gut has been linked to more pro-inflammatory immune cells. Image credit - Doc. RNDr. Josef Reischig, CSc.\/Wikimedia, CC BY-SA 3.0 \u0026lt;https:\/\/creativecommons.org\/licenses\/by-sa\/3.0\u0026gt;\u0022 height=\u0022655\u0022 src=\u0022\/research-and-innovation\/sites\/default\/files\/hm\/IMCEUpload\/lactobacillus_acidophilus_259_09_lactobacillus_acidophilus_doderlein_bacillus.jpg\u0022 title=\u0022Researchers found that high-salt diets reduce the amount of good bacteria found in the gut, and affect our immune system. Image credit - Daria Shevtsova\/Unsplash\u0022 width=\u00221024\u0022\u003E\n\u003Cfigcaption class=\u0022tw-italic tw-mb-4\u0022\u003EA smaller amount of lactobacilli in the gut has been linked to more pro-inflammatory immune cells. Image credit - Doc. RNDr. Josef Reischig, CSc.\/Wikimedia, CC BY-SA 3.0\u003C\/figcaption\u003E\n\u003C\/figure\u003E\n\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMetabolites\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EOn closer inspection, it appears that lactobacillus helps to keep the immune system in check by releasing compounds known as metabolites \u2013 by-products from its activity.\u003C\/p\u003E\u003Cp\u003E\u2018We could show that this effect (the increase in pro-inflammatory immune cells) is likely based on shifts in the metabolites which are produced by the lactobacilli, because they have an in vitro suppressive effect on the immune cells. If you have less lactobacillus, then the suppressive effect is gone,\u2019 said Prof. Kleinewietfeld.\u003C\/p\u003E\u003Cp\u003EThis research is still at an early stage, and further work is needed to understand the long-term effects of a high-salt diet on the microbiome. These studies were done in healthy volunteers, and so it will be necessary to carefully test the impact that changes in diet would have in a particular disease.\u003C\/p\u003E\u003Cp\u003EHowever, studying the microbiome is also yielding clues to the causes of autoimmune conditions without any treatments. One such example is primary sclerosing cholangitis (PSC). This rare disease causes blockages in the bile ducts, which in turn damage the liver.\u003C\/p\u003E\u003Cp\u003E\u2018It\u2019s very frustrating that we have no therapy but liver transplantation,\u2019 said Dr Johannes Hov from the University of Oslo in Norway. \u2018It\u2019s actually the most common indication for liver transplantation in Norway.\u2019\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EGut\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EThe cause of the condition is unclear, but there are signs that point to a link between autoimmunity and changes in the microbiome. Many patients with PSC have other autoimmune diseases, and some of the genes associated with the condition are also linked to autoimmunity. In particular, there is a strong link to the gut; up to 80% of patients also have inflammatory bowel disease.\u003C\/p\u003E\u003Cp\u003E\u2018This suggests to us that something going on in the gut is important for the disease in the liver, and this really points towards the microbiome,\u2019 said Dr Hov, who spends half of his time researching the causes of the disease and the other half treating patients in hospital.\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022https:\/\/pubmed.ncbi.nlm.nih.gov\/26887816\/\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003EPrevious studies\u003C\/a\u003E of the bacteria in the gut of PSC patients have found differences compared to healthy people.\u003C\/p\u003E\u003Cp\u003E\u2018So that is the starting point; the microbiome is different, but we really do not know whether this is causing disease, or whether it\u2019s caused by the disease,\u2019 said Dr Hov.\u003C\/p\u003E\u003Cp\u003EA partial answer to this question could come from studying people after their transplant. About a third of PSC patients develop the disease again within a few years, accumulating damage in their new liver.\u003C\/p\u003E\u003Cp\u003E\u2018I think that\u2019s fairly strong proof that there\u2019s something coming from outside of the liver that\u2019s attacking the liver,\u2019 said Dr Hov. \u2018It\u2019s really a unique opportunity to follow the disease from the beginning.\u2019\u003C\/p\u003E\u003Cp\u003EOne suggestion for the cause is a leakage of microbial metabolites into the bloodstream, which goes straight from the gut to the liver. However, finding which metabolites are contributing to the disease is a difficult task; Dr Hov describes the gut microbiome as \u2018a biochemical factory\u2019.\u003C\/p\u003E\u003Cp\u003EIn the \u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/id\/802544\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003EStopAutoimmunity\u003C\/a\u003E project, he is using hundreds of samples collected over the years from patients with recurrence and comparing them to those who were cured by transplant.\u003C\/p\u003E\u003Cp\u003EHe is screening blood samples for thousands of different metabolites to find any patterns linked to the treatment outcome. From analysing patient samples pre-transplant, he has already found significant changes in how they metabolise certain essential nutrients, including some amino acids and B vitamins.\u003C\/p\u003E\u003Cp\u003E\u2018So we speculate based on this, that the changes in the microbiome somehow reduce the access to essential nutrients, which could potentially influence the liver disease,\u2019 said Dr Hov.\u003C\/p\u003E\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003E\u2018You can really do something with a microbiome: you can change it, perhaps treat it. So if you have a disease with no treatment, then this is a good place to look.\u2019\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EDr Johannes Hov, University of Oslo, Norway\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EFaecal transplants\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EIf they find a metabolite that is driving the disease, then Dr Hov hopes that they could start a pilot trial to test therapies, such as probiotics or faecal transplants, to change the balance of gut microbes.\u003C\/p\u003E\u003Cp\u003E\u2018You can really do something with a microbiome: you can change it, perhaps treat it. So if you have a disease with no treatment, then this is a good place to look,\u2019 he said.\u003C\/p\u003E\u003Cp\u003EIt is this hope that is driving more researchers to examine the role of the microbiome in disease. However, the mixture of populations of microbes in our bodies is complex and variable. Even if researchers like Prof. Kleinewietfeld and Dr Hov can pin down the precise mechanisms at fault, the challenge remains of how to reliably fix it. The prospect of manipulating the microbiome could offer a way to treat many conditions, but we are still only scratching the surface.\u003C\/p\u003E\u003Cp\u003E\u2018I think there\u2019s so much more to come,\u2019 said Prof. Kleinewietfeld. \u2018But we are just beginning to understand how to use this knowledge in a therapeutic way.\u2019\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThe research in this article was funded by the EU. 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