ONE of the most compelling discoveries about the gut microbiome is its influence on the immune system. Between 70 and 80 per cent of immune cells are in the gut, where they are constantly communicating with microbes. This crosstalk helps fight disease, strengthen immune responses and regulate inflammation, our body鈥檚 first line of defence against infection. Controlling inflammation is critical, as too much damages cells and helps drive chronic illness.
It is no surprise, then, that a growing body of evidence implicates the gut microbiome in various chronic diseases, from arthritis to Alzheimer鈥檚. It is still early days, and most of these findings only point to associations. But they raise the possibility that gut microbes may contribute to, or even cause, some of our most intractable conditions, an idea that has already inspired new treatments.
It is now well established that gut microbiomes in people with conditions like multiple sclerosis, type 1 and type 2 diabetes, Parkinson鈥檚 disease and even asthma differ significantly from those of people without an underlying illness. Two papers published earlier this year showed that people with chronic fatigue syndrome 鈥� also known as myalgic encephalomyelitis, or ME/CFS 鈥� have less of a gut bacterium called Faecalibacterium prausnitzii in their stools. This species produces anti-inflammatory molecules, so a deficit of it could explain the excess inflammation seen in the condition. Low levels of F. prausnitzii are also seen in the guts of people with inflammatory bowel disease (IBD), a group of disorders characterised by chronic inflammation of the digestive tract, and in children susceptible to type 1 diabetes.
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There are hints that gut bacteria may even be at play in Alzheimer鈥檚 disease, which seems to be exacerbated by chronic inflammation in the brain. A showed a lower abundance of multiple inflammation-dampening bacteria in the guts of people with Alzheimer鈥檚 compared with those without it.
Pathogenic gut bacteria can also shift during chronic illness. People with rheumatoid arthritis 鈥� a disease in which the immune system mistakenly attacks joints 鈥� have in their stools than those without it. Subsequent studies have found that C. aerofaciens increases levels of a pro-inflammatory molecule in human intestinal cells that is known to play a role in rheumatoid arthritis.
There are three leading ideas as to why the gut microbiome can become disrupted in chronic disease, says at Emory University in Georgia. The first is genetics, which could promote different environments in our guts, he says. For instance, mutations in genes associated with IBD affect . In mice predisposed to IBD-like symptoms, those lacking one of these genes, called NOD2, were more susceptible to developing signs of the condition.
Environmental toxins
A second explanation is to do with environmental toxins. Previous research has linked exposure to common pesticides with an increased risk of some neurodegenerative diseases like Parkinson鈥檚. It is possible these chemicals are also responsible for the microbial disruptions found in those with the condition, says Sampson.
Finally, alterations could be related to a preceding infection. For example, many people with ME/CFS report their symptoms beginning after a viral infection. Such infections may cause lasting disturbances to the gut microbiome that then help drive a chronic disease, says Sampson.
Understanding what leads to disruptions in the balance of our intestinal residents could help answer the more critical question of whether these shifts then propel disease. 鈥淥ne of the difficult challenges is understanding what鈥檚 coming first. Is the microbiome composition changing prior to the disease diagnosis? Or is it something that arises as the disease progresses?鈥� says Sampson. Studies in animals seem to suggest the former. For instance, Sampson and his colleagues have found that transferring gut microbes from people with Parkinson鈥檚 disease into mice that are genetically predisposed to symptoms of the condition significantly . He and his team have also shown that, in mice susceptible to Alzheimer鈥檚-like disease, those without a gut microbiome have in their brains than those with gut microbes.
Faecal transplant treatment
Whether these animal studies translate to humans is an important next step. One way of testing such ideas in people is by performing faecal transplants from a healthy individual to one with a chronic disease. If symptoms of the disease lessen afterwards, it indicates that the microbiome was driving pathology in some way. Very few of these studies have been conducted, and so far most of those focused on IBD, but their results are promising. Across 36 studies in people with the condition, faecal transplants led to remission in in 54 per cent.
Understanding how gut microbes contribute to chronic disease may lead to other, more practical ways of treating such illnesses. Taking probiotics, which are foods or supplements that contain beneficial live microbes, or consuming a diet that supports beneficial, anti-inflammatory bacteria could help alleviate symptoms of inflammation, for instance. Alternatively, new medications that somehow alter the workings of the microbiome could do the trick. Already, Stanley Hazen at the Cleveland Clinic, a healthcare institute in Ohio, and his colleagues have developed an that prevents microbes from producing a molecule called trimethylamine N-oxide, or TMAO, a known driver of heart disease.
鈥淓ven if the microbiome itself is not contributing to [chronic disease], by acting on it through drugs or probiotics, we can make the microbiome promote a beneficial function,鈥� says Sampson.
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Speak to your doctor before seeking new treatments for medical conditions.
This article is part of a special series on the microbiome, in which we explore:
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