Dysbiosis happens when the gut microbiota becomes imbalanced, or ‘out of kilter’. The most common causes of an imbalance are a loss of beneficial microbes, excessive growth of harmful microbes, or a general loss of microbial diversity. Dysbiosis can lead to a wide range of digestive illnesses, including gut inflammation, inflammatory bowel disease (IBD) and colorectal cancer.
Our researchers are investigating the causes and effects of dysbiosis. Working with Prof. Chen Wei and colleagues from Jiangnan University in China, researchers in the Narbad Group discovered that a new sulphate-reducing bacterium (SRB) can convert nitrogen into a biologically useful form. Until now, SRBs have been commonly associated with digestive illness.
There are around 250,000 people in the UK with Myalgic Encephalomyelitis (ME), also known as Chronic Fatigue Syndrome (CFS). It causes widespread pain, extreme fatigue, an inability to concentrate and for a large proportion of people, gut disorders such as Irritable Bowel Syndrome (IBS).
The Restore-ME trial, led by Prof. Simon Carding with NNUH, University of East Anglia (UEA) and funding from Invest in ME, is investigating the link between dysbiosis and ME/CFS. The study will test whether the use of Faecal Microbial Transplants (FMT) can restore the microbiome in ME/CFS patients and relieve symptoms.
The gut-liver axis is an exciting area for research, particularly as we increasingly understand more about how the gut microbiome influences health. Cholestasis is a common symptom of chronic liver disease. Researchers have found that the microbiome is different and less diverse in patients with cholestasis. Some cholestasis patients also show signs of a ‘leaky’ gut, and inflammatory bowel disease. These associations give clues to how cholestasis develops. To investigate further, Dr Naiara Beraza led a study into the interactions between gut microbes and cells of the immune system that contribute to cholestatic liver disease.
Maintenance of a healthy gut microbiota
Understanding how differences in populations of bacteria and other microbes influences the functional role of the gut microbiome in human health is crucial. Gut bacteria break down carbohydrates using glycoenzymes; different bacteria have different types of glycoenzyme, each one being specific to a certain carbohydrate.
Prof. Nathalie Juge leads a team investigating these glycoenzymes, and how their specificity for certain carbohydrates suits them to different roles in the gut. The team identified an enzyme that helps particular bacteria colonise the human gut by giving them access to breast milk sugars and intestinal mucins. The Juge Group also discovered that the sugars in milk, called human milk oligosaccharides (HMOs), can improve ‘leaky’ guts.
In addition to the other benefits, a healthy gut microbiome also helps us fend off invading pathogens, the microbes that can cause disease. They can outcompete them for nutrition and space to colonise in the gut, preventing any invaders from accessing the gut lining and getting into our blood stream.
They also produce a range of compounds that inhibit pathogen growth, including Short Chain Fatty Acids (SFCAs) and bacteriocins (proteins that limit microbial growth) The Narbad group recently found a strain of Lactobacillus in human breast milk that makes an arsenal of bacteriocins and SFCAs that could be key to helping maintain a healthy microbiome.
The gut microbiome and breast cancer
Breast cancer is the most common type of cancer diagnosed in women in the UK, but the prognosis is good if diagnosed early. Although gut microbes seem like unlikely heroes in the fight against breast cancer, several studies have indicated that they can actually boost cancer therapies. They may also be biomarkers indicative of cancer progression that can be used to screen cancer patients.
The BEAM study, led by Nancy Teng, is one of the few trials so far that is exploring the gut microbiome and breast cancer.
Recent research shows that the gut microbiome influences the outcome of cancer therapy by modulating the host inflammatory response. This suggests a direct correlation between microbe-mediated immune reactions and the efficacy of a group of drugs called immune checkpoint inhibitors; these include the commonly used drug, pembrolizumab.
The groups of Prof. Lindsay Hall and Dr Stephen Robinson have joined a collaboration to investigate whether the microbiome can be used to predict how breast cancer patients will respond to immunotherapy. It’s hoped that this will help tailor future treatments, by personalising them for each patient.