The 3rd Microbiome R&D and Business collaboration forum – Europe – was held in London on 11th and 12th April 2016. Here is a copy of the Microbiome Q&A I wrote for the event:
What aspect of microbiome research are you focusing on at the moment?
The research performed in my group focuses on the exploration of the metabolic cross-talk between the gut microbiota and its host. Our projects therefore span across a wide range of issues, from investigation of host-pathogen interactions in broiler chicken to the role of bacteria in type 2 diabetes.
More specifically, we have just started to look at the influence of some milk-derived bioactive peptides on the gut microbial ecosystem, as this has been suggested as a potential mechanism associated with the development of diabetes and autism. We are also involved in the largest EU-funded project exploring the links between gut microbes, obesity and behaviour (www.mynewgut.eu). Our specific role within this consortium is to characterise the metabolic changes associated with gut microbial manipulation and diet intervention in human volunteers. This contributes to identify the biological mechanisms underpinning these modulations and their potential benefits on health.
Another exciting project that keeps us busy at the moment is the development of a mouse model exposed during gestation and in early life to a diabetic microbiota. By carefully controlling the bacteria to which the animals are exposed, we will be in a position to study the role of gut microbes on the metabolic imprinting that is thought to influence the development of metabolic disorders later in life. This will also allow us to identify the precise mechanisms of action (i.e. metabolic pathways) that are specifically influenced by microbes during this very plastic window in early life. We will then be able to propose new diet supplements or functional foods that may rescue these metabolic perturbations. These should be simple interventions that aim to be easily transferable to humans for a more personalised approach of functional foods.
What are going to be the big challenges in developing treatments based on the microbiome?
In my opinion, the biggest challenge we are facing at the moment in developing treatments based on the microbiome is the lack of understanding of the biological mechanisms that regulate bacteria-host metabolic interactions. A lot of effort is going into this worldwide, but it is extremely challenging due to the complexity of the gut microbiota and their high variability from one individual to another. Human beings are also genetically diverse, which adds another layer of complication. We do a lot of research using artificial gut models but they do not reflect some important physiological aspects of human metabolism. We also use animal models, which are very useful to identify specific mechanisms of interaction but translation to humans is limited. Finally, even small diet interventions performed on human volunteers in a laboratory setting can be difficult to extrapolate to the general population. To address this challenge, we need to better understand the human microbiome variability so that we can stratify people based on their gut symbionts and on their metabolic status to design more personalised functional foods. I firmly believe that this is the only way to approach such a complex diversity.
Another challenge we face is the legal framework that do not authorise the commercialisation of genetically engineered microorganisms. This evolution will be necessary to develop the next generation of live microorganisms that may be designed to deliver a drug (such as an enzyme) that cannot be chemically synthesised and needs to be embedded in a live organism to be functional.
What form will the first fully commercialised microbiome drug take?
It is difficult to anticipate which microbiome drug will be first on the market, but it looks like the development of targeted cancer therapy is well advanced. There is a fascinating body of work demonstrating the role of the commensal flora in regulating the immune response that contributes to the specific killing of tumour cells. A recent study published in the ISME Journal demonstrated that the life of mice affected by leukemia could be significantly prolonged when they were treated with a synbiotic (i.e. a mixture of a live probiotic and a prebiotic). These are very exciting results that indicate the potential for microbiome modulation in cancer treatment.
How overhyped is the microbiome?
When making claims about the microbiome, we must remember that every individual is microbially unique and a one-size fits all approach cannot work. A probiotic that replaces a lost function in one individual may be extremely helpful for this person but totally useless to another who already carries the function. This is true for all probiotics. Boosting lactic acid producing bacteria in people who are deficient in this category of bugs may help them fight against opportunistic pathogens and preserve them from developing diarrhea but this will be totally inefficient in another group of individuals who already have a healthy balance of this group of bacteria.
What will the microbiome space look like in 5 years’ time?
In 5 years time, I hope we will have made good progress in terms of understanding the biological mechanisms underpinning gut microbes-host interactions. We will likely have a better picture of who is there and what they do. Many consortia are actively working on this and will have published their findings by this time. Perhaps we will also see emerging the first genetically engineered microorganisms, although this may be more for the next 10 years.