Microbiome research and causality

Clinicians and biologists try to find correlations between the gut microbioma and health outcomes. Very often no causal link is found. If one is ill for long time, chances are that medications were used regularly, and if one is obese, chances are that he/she ate unhealthy for long time. These factors will influence the onset of the disease and the gut microbioma composition. Even more, other factors like country of origin and the genetic background will also play a role in the gut microbiome composition and in the chance of developing certain diseases. The main challenge is to find out the right changes in the gut microbiome that actually play a role in the disease. Is then the fact that, in a dataset of thousand of bacteria, some of them show a correlation with the disease real or based on sheer coincidence?

A good example of causal relationship between the gut microbiota composition and the development of a disease is fecal macrobiota transplantation. This strategy was applied for patients with Clostridium difficile infections and the results were good, as this microorganism is able to thrive in people with disturbances in their gut microbioma, but a fecal transplant of a healthy gut microbiome composition will restore the balance and get rid of C.difficile bacteria. Another interesting development in the study of the healthy microbiome shows that the bacterium Akkermansia Muciniphila is abundant in healthy people but often absent or low in human or mice  with obesity. If you feed them with A. muciniphila, a relation between the bacteria and the metabolic health of the host is noted, and a positive effect on health balance and metabolic rate. An ongoing clinical trial with pre-diabetic patients is done right now in order to confirm those positive effects.

Other option to study causal relations between gut microbiome and health can happen in laboratory, using germ free mice, and exposing them to specific bacteria to test the effect on metabolism, digestion or immune system. But we cannot have a decisive answer using these methods, and a clinical trial using an appropriate group of patients is always needed, hopefully resulting in personalized treatments against diseases, taking into account the differences in our microbiome.

Microbiota is defined as everything staying in our gut, small enough to not be seen with naked eye (bacteria, archaea, fungi and viruses) and their habitat. Microbes form our gut play a role in all kind of systems to good liver access, good brain access, good skin access. The microbiota is personalized, everybody has a different microbiome. Monozygotic twins are more similar than average unrelated individuals in terms of microbiome, and this can be because genetics or same time colonization. The microbiome develops through life, so some of our actions will impact later in life (as repeated use of antibiotics for example). We have an enormous number of associations between our microbes and our cells activities, but no casualty (the famous example with recurrent C. difficile patient in intensive care and almost dying being rescued by fecal microbiota transportation in a systematic way, much better than antibiotics).

We got MetaHit project, with over 3 millions genes discovered in the guts of a couple of people, aiming to understand what is it there in our microbiota, but also what is their function, how they are expressed, how they are collaborating and constituting this ecosystem that makes us healthy. There is a symbiosis relationship (Venom is a great movie about symbiosis, by the way) and we feed the microbes that we want to have in our gut. As important hallmark of our discoveries in the last couple of decades, Akkermansia Muciniphila (the gatekeeper of mucus) reinforces our gut barrier and prevents substances like LPS to come into our bloodstream.

In the next posts i will talk about the early life microbiota development.
Have a nice day!
G.