Microbiota - The faecal microbiota transplant

The faecal transplant os a very good tool to prove a causative role of our gut microbiome in curing different diseases. Because of this reason, the interest in faecal microbiota transplant is rising. We mentioned some research done on mice, but this is a well known practice, and we have a Chinese medical manual from the 4th century A.C. describing the procedure done on humans, as a remedy for food poisoning. But how do we do it today? A healthy donor donates a stool sample, which is tested for certain diseases, frozen and given to the patient later by a tube or as capsules, in order to reach the small intestine. Enema can be also used. This is working by restoring a gut microbiome that it is out of balance, bringing equilibrium and leaving hardly any room for pathogens. However, use of antibiotics and some other factors can disrupt the balance, allowing the pathogens like clostridium difficile to cause infections (symptoms are chronic gut inflammation and persistent diarrhoea). Using antibiotics to cure an infection with clostridium difficile is not effective, as the disease is recurring, and the bacteria is becoming resistant to antibiotics, because this clostridium difficile can colonize an altered microbiota composition. By restoring the microbiota composition, 90% of the patients were cured.

In this case, the faecal transplant is more efficient that antibiotics. Because the gut microbiota of a healthy donor is introduced, restoring the balance and breaking the cycle of the disease. When the healthy microbiota colonize the inside, no more room is left for Clostridium Difficile. Small results were also found in patients with diabetes type 2. Many scientists work to replace the fecal transplants with an odourless mix of bacterial strains derived from the human fecal material.

Do not try this at home, does not matter how many Youtube video you see about this.

The following post will be about the next generation probiotics.

See you soon!
G.

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.