Accuracy of the director of the publication :
The content of news and the approach of the science collaborative, encouraging, and we will cover this topic. In confinement, the people have had time to deepen their research and delve into the scientific literature. They do not call in question the state of the science, but allow themselves to get off the beaten track to make assumptions and seek to validate them. We are once again in the thesis of the initial internet, which put in advance the collaborative research and the contribution to the resolution of a medical problem. The work of these people are published to demonstrate their desire for contribution. The gray matter exists, and it is interesting to make use of it.
ANALYSIS : The correlation is not equivalent to causation
Many people, driven by anxiety for their relatives, and anxious to contribute to the scientific debate , have questioned the correlation observable between certain aspects of the Covid-19 and the bacterium Prevotella. The bacterium Prevotella, and its sub-species (Prevotella spp.) are, in fact, an echo in the epidemiological profiles and the tables of symptoms of the Covid-19 . However, a bit like the popular saying which states that ” comparison is not reason “, the correlation cannot be assimilated to a causal link. In other words, this is not because the symptoms of the Covid-19 evoke Prevotella this bacterium is the cause. It is for this reason that the track Prevotella was ranked a little too quickly to the rank of ” Fake News “. In any rigour, before you classify it as such, the hypothesis to validate is : is there a possible link of causality ?
To our knowledge, this work has not been done. We propose only to alert the reader and the researchers on the possibility of a causal link between Covid-19 with Prevotella (and the microbiota in general) through its interaction with the angiotensin-converting enzyme 2 (ACE2 to the abbreviation that we will use later), the door of entry of SARS-COV2 (this term refers to the virus, the Covid-19 the disease) in the body. An enzyme is a special type of protein that has catalytic properties, that is to say, properties that turn a molecule into a different molecule final (more precisely, it speeds up this reaction).
We sought to investigate the possibility of causal
Tastuo Hashimoto, Thomas Perlot and their team, published in 2012 in the prestigious journal Nature, a study on the enzyme ACE2. The assumption is the following : the onset and severity of symptoms of the Covid-19 is indirectly influenced by the microbiota, because the latter influence the expression of the enzyme ACE2. Therefore, it is not forbidden to think that the bacterium Prevotella may play a role in the Covid-19.
The enzyme ACE-2 is the main entrance door of the Covid-19
The enzyme ACE-2 is the main entrance door of the Covid-19
Without going into the details of the molecular biology of the cell, we identified two proteins that enable the virus to bind with molecules . The first , which seems to be anecdotal for the moment (maybe in the future the deny) is the protein hemagglutinin esterase (HE). The second, which allows the virus to bind with other molecules is the protein Spike (or S protein). The term Spike means “spike” in French (a kind of tip). It refers to the idea that the virus has literally cornered or is on file in the protein (molecule) of the cell it will attack.
In the case of the Covid-19, the Spike protein is to bind to a protein of certain human cells that are called “angiotensin-converting enzyme 2” (ACE2 to the English abbreviation).
In our case, the enzyme ACE2 are present on the epithelia, tissues that are found in certain parts of the body. These epithelia can be of several types : epidermis (skin epithelium) , intestinal epithelium, respiratory tract epithelium, epithelium of the bladder and urinary system. The distribution of the enzymes ACE2 provides a basis of explanation of the symptomatology of the Covid-19.
In summary, SARS-COV2 comes to bind strongly to the enzyme ACE2 of human cells that have, and use those cells to multiply, then leaving behind the dead cell.
It would be therefore tempting to conclude that the more cells ACE2, the more doors to entries for the Covid-19 and the more we will be affected severely. But it is not. In other words, scientists do not yet manage to highlight links of correlations of the quantitative logic between the amount of epithelial cells (and therefore of enzymes ACE2) and the severity of the symptoms.
The microbiota modulates directly the expression of the enzyme ACE2
An experience of the aforementioned study, we are particularly interested in. It allows you to highlight the direct causal link between microbiota and expression of this enzyme ACE2.
The researchers studied two mice, one mutant (sick), the other healthy. The mouse mutant of this enzyme ACE2 dysfunctional, which causes a dysregulation of the renin-angiotensin system (system regulation of cardiovascular functions and lung). The other mice do not present any dysregulation of the renin-angiotensin system and its enzymes ACE2 seem to work properly.
The researchers then transplanted the microbiota of the mice sick to the healthy mice : they then observed that the enzyme ACE2 became dysfunctional and was causing a dysregulation of the renin-angiotensin system.
The study also demonstrates that the ACE2, when it is dysfunctional, plays a role in some inflammatory phenomena. As a result, the study allows to conclude that, most likely, the microbiota modulates directly the expression of the enzyme ACE2, which can cause inflammatory phenomena.
We can therefore hypothesize that it is the same in the disease of the Covid-19 and it is not clear why the infection of a human cell by the Covid-19 would neutralize the influence of the microbiota on the expression of the enzyme ACE2.
Some bacteria have a more prominent influence than others in the expression of the enzyme ACE2
In the aforementioned study, the researchers will test several hypotheses. They show that the absence in the diet of the host, an essential amino acid (one of the fundamental building blocks for the production of proteins, and that the body can not synthesize), in this case tryptophan, disrupts the activity of the ACE2.
They also observe that when the enzymatic activity of ACE2 is disrupted, it leads to inflammatory phenomena. They show that the absence of an amino acid (one of the fundamental building blocks that makes up a protein), in this case tryptophan, disrupts the catalysis of the ACE2. At the same time, the authors found a dysregulation in the decrease of anti-microbial peptides, which play a role in the immune response to kill Gram-negative and Gram-positive (Gram positive or negative, defining a type of structure at the level of the wall of a bacterium).
In other words, the disruption of the enzymatic activity of the ACE2 by the microbiota causes both inflammatory phenomena, but also a decrease of the immune response to bacteria.
In contrast, transplantation of the microbiota of the mouse mutant (sick), to a healthy mouse did not result in a decrease of the immune response to bacteria. It is therefore the disruption of the enzymatic activity alone that lowers the immune response to bacteria and non-intestinal flora.
The immune response playing an essential role in the disease and its complications, it would therefore be interesting to determine the share of responsibility of bacteria to inflammation, when compared to the viral. In their study, the scientists are trying to see what bacteria are most likely to benefit from the timely manner of this weakening of the immune system.
To do this, they use in the course of their experience of the rapamycin (an immunosuppressant) for the purposes of the experiment. They concede that this introduces a bias analysis in the microbiota and that for these reasons the analysis is not completely reliable. The researchers conclude that some bacteria may become more abundant than others, in the absence of activity of ACE2, either with or without tryptophan in the diet of the host.
The researchers were mainly identified : bacteria Limibacter : bacteria are aerobic (they need oxygen to survive), Gram-negative, bacteria Plaudibacter : anaerobic bacteria (they thrive in oxygen-free atmosphere) Gram-negative, bacteroidales unclassified
Prevotella copri is a track preferred because it has been identified as a bacterium discriminant of the microbiota
The SARS-COV2 helps to disrupt the activity of the enzyme ACE2 in the binding. But, each situation is different and the experience described, even if it allows to draw certain conclusions, does not represent a of the general case. In this case, given the fact that the SARS-COV2 has a material particular genetic and causes an immune reaction specific, it seems impossible to be able to make analogies on this study to draw lessons on the bacteria at work in the host in the context of this disease.
However, the expression of ACE2 is directly dependent on the microbiota, it appears that the microbiota is likely to be the discriminating factor tables of symptomatologies of the Covid. Gold Prevotella, bacteria discriminant of entérotypes (bacterial profile of microbiota) as a first approximation, may be a bacterium candidate and play a major role in the Covid-19. It can explain fairly well the profile of the epidemic and some of the symptoms encountered .
SARS-COV2 could also prepare a favorable ground for bacterial infections of Gram type-negative (not that this is necessarily the bacteria Prevotella).
Moreover, if the track of Prevotella spp. were to be confirmed, the treatment of substance useful against this type of bacteria may be:
- anti-inflammatory against rheumatoid arthritis (Tocilizumab, Hydroxychloroquine…)
- against cystic fibrosis (antibiothérapies)
- disease Crohn’s targeting this bacterium
- based probiotics designed to boost the competition of bacterial
Even more simply, a change of diet.
References and acknowledgements :
 Including Bio Moon and Sandeep Chakraborty
 ” ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation ” https://www.nature.com/articles/nature11228#Sec20
 Thanks to Alexander Samuel, a Doctor of molecular biology (and author of several publications related with the neuro-development), for having been with me in my approach and have allowed me to express my hypothesis in a specific language.
About the author : Igaal Hanouna is passionate about biology, a graduate of Sciences Po and Sup de Co Paris.
Author(s): Igaal HANOUNA for FranceSoir