There has been much talk recently about the microbiome, the trillions of microbes that live on and within us, sharing our lives in health and disease. From aiding in the digestion of our food and priming our immune system for response to preventing pathogen invasion, significant benefit can be gained from these symbioses. Yet, an altered microbiome can cause disease, having been linked to metabolic disease1, obesity2, diabetes3 and colonic cancer4.
Earlier this year the National Institute for Health and Care Excellence (NICE) backed the use of faecal transplants for reoccurring infections of Clostridium difficile as safe and effective. Colonisation of the gut by C.difficile can lead to vomiting, diarrhoea and abdominal pain. In some cases it can be fatal.
Antibiotics have shown to be of limited use in tackling blooms of this bacteria in approximately 25% of patients. Instead the infusion of healthy faecal matter into the gut has been shown to help re-address the balance of the microbiome within the intestines, promoting the growth of ‘good’ microbes once more and eliminating the growth of C.difficile. This treatment is effective in 90% of patients.
As we increase our knowledge of this vast community of microbes by which we are surrounded, hope is raised at the possibility of easy intervention through the use of probiotics or faecal transplants to treat the ever increasing burden of disease, with some stating that the microbiome offers ‘the only organ that can be replaced without surgery’.
But the microbiome is dynamic: research by Dr Patrick Schloss from Michigan University showed that the microbiome of 300 individuals all showed comparative differences with changes occurring in their microbiome for as yet unknown reasons5. So, though we cling to the desire for simple panaceas that will bestow good health with minimal effort, it seems biology is rarely that charitable.
Recent investigations into the effect of the microbiome on arthritis in mice demonstrated that the secretion of the pro-inflammatory cytokines IL-1? and IL-6 was diminished following antibiotic administration, resulting in a milder arthritic response compared to controls6. An increase in inflammation was then observed following the transplantation of faecal matter from control mice into antibiotic treated animals. This suggests that the recolonization of the gut microbiota of antibiotic treated mice with microbes from the control mice promoted the increase in arthritis symptoms. Faecal analysis of the antibiotic treated mice showed an ablation of all bacterial species except Lactobacillus, Klebsiella and Sutterella.
Both IL-1? and IL-6 promote Breg cells to differentiate and produce IL-10, which then acts to curtail inflammation and keep this response in check. Antibiotics given to the mice reduced the differentiation of Breg cells. This limited the secretion of IL-10 preventing the limitation of the inflammatory response. Thus inflammatory signals from both the gut microbiota and arthritis control the differentiation of Breg cells and the inhibition of further inflammation by IL-10. The researchers concluded that commensal microbiota is important in establishing pro-inflammatory and regulatory responses and maintaining equilibrium to allow the immune system to promptly clear infections yet minimise any collateral damage.
Increasing knowledge of our immune system will aid our understanding, but the work being carried out in this field shows that we need to also keep in mind the interactions taking place between our own biology and the ecosystems within our body. The microbiome has developed both symbiotic and disease causing functions over time and we must penetrate this diversity and complexity if we are to sculpt it to our advantage.
References1. Vikay-Kumar et al. (2010) Science 328 (5975); 228-231. 2. Turnbaugh et al. (2006) Nature 444; 1027-1031. 3. Devaraj et al. (2013) Clinical Chemistry 59 (4); 617-628. 4. Yang and Pei (2006) World J Gastroenterology 12 (4); 6741-6746. 5. Ding and Schloss (2014) Nature 509; 357-360. 6. Rosser et al. (2014) Nature Medicine 20; 334-1339.