Recent scientific studies have revealed how the billions of bugs in our gut influence our BMI and immune system. To establish links between our genes, the bacterial environment in our gut and diabetes, Luxembourg’s researchers have embarked on two pilot research projects supported by IBBL (Integrated Biobank of Luxembourg) and the LCSB (Luxembourg Centre for Systems Biomedicine).
It is widely accepted that a combination of the environment and our genes is responsible for many diseases. In recent years a third player has come to light: the microbiome. This term has been used to describe all the microorganisms living in a given environment, for example the human gut. Given that the number of microbial cells largely outweigh the number of human cells it is not surprising that the former actually play an important role in human health. Indeed over the last five years links between the microbiota in the gut and diseases such as Clostridium difficile infections, irritable bowel syndrome (IBS), Crohn’s disease and even obesity have been established.
Even though the field of human microbiome research has made major progress, we still do not fully understand how and why these microorganisms cause disease. However, it seems that the composition of the whole microenvironment and the balance between different species can make the difference between health and disease. This is especially true for the gut, where, the more bacterial diversity is found, the healthier you will be, at least when it comes to your waistline. Indeed two studies from the MetaHIT consortium (http://www.metahit.eu/) published in Nature this August linked reduced diversity in the gut microbiome to obesity and inflammation, and showed that dietary intervention in overweight people can improve diversity in certain individuals [1].
Dr Le Chatelier and her colleagues analysed the microbial composition in the gut of 292 Danish individuals, about half of which were obese. They then classified the individuals into two groups; those with high bacterial diversity and those with low bacterial diversity. The authors reported that individuals with lower diversity had a higher percentage of body fat, abnormal amounts of lipids in the blood and were more insulin-resistant. The combination of these factors puts these individuals at a higher risk for diseases such as diabetes or cardiovascular diseases. Perhaps not surprisingly, the individuals with a less rich gut microbiome also showed a more pronounced inflammatory phenotype. Indeed previous studies have already suggested the impact of the microbiome on inflammation. Chronic inflammation of human tissue has been linked to the development of wide range of diseases from cancer to diabetes.
One key mediator of the microbiome’s effect on inflammation appears to be regulatory T-cells. This subset of white blood cells is crucial in keeping the human immune system at bay by preventing excessive immune responses, particularly to the body’s own cells. Recent evidence shows that certain strains of bacteria can lead to an enrichment in T-cells thereby promoting an anti-inflammatory state. In collaboration with Dr Paul Wilmes from the LCSB (Luxembourg Centre for Systems Biomedicine) researchers from Japan recently showed that treatment with specific bacterial strains that induce a strong anti-inflammatory response may be a good rationale to restore balance in the microbiome and combat certain diseases which exhibit a marked inflammatory signature [2]. In their work, the authors isolated 17 bacterial strains, which were particularly potent in increasing the number of regulatory T-cells. These bacterial strains managed to attenuate disease in mouse models of colitis and allergic diarrhoea when administered orally.
This study is a prime example for the great promise that research in to the human microbiome holds, in particular, because it can potentially be easily moderated through intervention (diet, probiotics, fecal transplants). However, before any of these interventions make their way into the clinic it is important to further elucidate the complex network of interactions between the bacterial communities and human cells. On this basis, IBBL (Integrated Biobank of Luxembourg) currently supports two microbiome research projects, led by Dr Carine de Beaufort (Centre Hospitalier de Luxembourg/LCSB) and Dr Paul Wilmes (Luxembourg Centre for Systems Biomedicine). The first study focuses on families where more than one family member has diabetes mellitus. The aim is to compare variations in the human genome and composition of the microbiome between individuals. The second project studies the development and evolution of the microenvironment in the gut of babies and how this might influence the development of diabetes later in life. In addition to co-funding the projects, IBBL is collecting a range of samples, including blood and stool, from voluntary participants, with the help of the Clinical and Epidemiological Investigation Center (CIEC) at CRP-Santé. Other projects on the microbiome are being initiated between Luxembourgish research groups and IBBL as this topic is part of IBBL’s strategy in the coming years.
Anyone who is pregnant or has diabetes and is interested in participating in one of these studies can contact IBBL at (+352 27 44 64 -1) for more information.
[1] doi:10.1038/nature12506 and doi:10.1038/nature12480
[2] doi:10.1038/nature12331
Photo © National Institute of Allergy and Infectious Diseases (NIAID)