Two years ago, I attended a lecture at the Annual Microbiology Society Conference, in Edinburgh. A young researcher, Dr Katharine Coyte from Memoral Sloan Kettering Cancer Center in New York, gave a talk about the human microbiome, from an ecologist’s point of view. The room was full with microbiologists and molecular biologists and many of us, including myself, initially struggled to understand the terminology that she used about the ecological networks and the evolution of microbial communities. But when she said that our intestine is like a tropical rainforest, suddenly everything made sense.
And then I realised that we still know nothing (or perhaps very little) about what really happens in our gut.
Although our gut is not as big as the Amazon Forest, and the organisms that it harbours are mere microbes and tiny parasites, not tigers and anacondas, it still contains many thousands of different microbial species, most of them still unknown to us. When we use antibiotics, many of these species die and it is difficult to know exactly which ones. It is like starting a forest fire or blindly bombing the jungle. The balance of the forest is disturbed, and the ecological networks are disrupted (preys, predators, symbionts and parasites). If the predators die, the prey overpopulates the intestine and if the prey dies, the predator starves. Some bacteria, such as Clostridium difficile, that are called opportunists, exploit this change and lead to disease (because chaos is a ladder!).
Similarly, when someone introduces a new species into the forest (i.e. a probiotic), it first has to survive, adapt and colonise the gut and this might not always be easy. If its colonisation is successful, how does it affect the already established communities?
The medics, the nutritionists and the microbiologists that work on microbiome research are often focused on direct health effects and they forget that they deal with a complex and still unknown ecosystem. On top of that, the probiotics industry wants new effective products, often making big claims about a product’s miraculous effects, without solid scientific evidence about the biological mechanisms involved or the potential risks of their intervention. Sometimes probiotics do work, but how and to what expense? We have recently seen in the news that some of these products often have unexpected adverse effects.
Most of the published research papers talking about our gut microflora are mainly focused on bacteria. What about the other microorganisms present in our gut? What about viruses, fungi, protozoa, microalgae and worms? We still do not know how they affect the balance of these complex communities. Choosing to ignore them, is like an ecologist trying to fully understand a tropical ecosystem but forgetting to study birds and insects. In addition, there are thousands of bacterial species that either cannot be cultured under laboratory conditions (they are collectively called ‘microbial dark matter’) or have not been studied yet. Are they important? Are they producing beneficial or harmful metabolites?
Finally, this dynamic microbial ecosystem is affected by a multitude of factors, such as our dietary habits, medical treatment (e.g. prolonged use of antibiotics or immunosuppressants), interactions with our immune system and even our genetic background. Some links have been established the last twenty years, but do we have a full understanding of these interactions? No. It is like trying to fix a broken watch, without knowing exactly what is inside it.
It seems that we started suggesting probiotic-based health interventions too soon. We need to have the full picture about these communities work. Like the brain, our gut microflora is a complicated organ and it might take a few more decades before scientists fully elucidate all the important associations and mechanisms. The probiotics industry was too eager to commercialise supplements with good bacteria, blindly suggesting their use as a panacea against all ailments, just like the use of leeches in the Middle Ages.
Perhaps the probiotics companies wanted to mimic the commercial success that the vitamin- or trace element-containing supplements have. The difference is that we now know most of the essential metabolic reactions in our cells that are affected by vitamins, iron, calcium, etc. This was not easy. It took the biochemists more than 40 years (from mid-1910s to late 1950s, resulting to three Nobel Prizes). Hopefully, it will not take that long to understand how our complex intestinal ecosystem works.
This is because we now have very advanced molecular technologies, well-populated genomic databases, sophisticated computer software and mathematical modelling methods that can help us doing better research, making more confident predictions based on detailed and validated models and effectively applying personalised therapeutic interventions based on solid scientific evidence. This is the way forward!
By Dr. Georgios Efthimiou, microbiology lecturer at the University of Hull, UK. His research focuses on the interactions within the human microbiome, the formation of microbial biofilms and the biosynthesis of microbial products that are beneficial for human health.