Five Key Questions When Interpreting Scientific Literature:

• Can experiments detect differences that matter?

In this article, the author points out that it is important to not put the cart before the horse, so to speak, when identifying the presence of certain genetic sequences and concluding what their existence in a certain situation means.   The reason scientists are able to conduct more sophisticated experiments and see causal relations between the presence of microbes, genetic sequencing, etc. and human diseases is because of the newer technology of 16S rRNA sequencing and identification.  The author points out that there are limitations when using this method in experiments, and that sometimes results can cloak finer causal relationships between gene combinations that we don’t necessarily see with this method. He further points out that our understanding of specific genes in the gut microbiome is a result of anecdotal evidence, and so it is dangerous to conjecture cause and effect relationships, in some cases invalid to do so, because in doing so we may be overlooking genetic sequencing or functional differences between genes that are not identified ahead of time.

• Does the study show causation or correlation?

This is a basic concept  that can, in the field of microbiome research,  skew many scientific methodologies and conclusions that are drawn from the data.  This is primarily because we still don’t have a good understanding of the mechanisms of the symbiotic relationships between the gut microbiome and human diseases and conditions. Scientists may see patterns, and offer a causal relationship, but there are often other factors that may contribute to or cause a particular condition.  For example, in studies suggesting that an infant born by C-section may be more susceptible to allergies as an adult than a vaginally delivered infant because of the adverse effects on the early establishment of a healthy microbiome, one would have to consider many other environmental factors and control for those in any study, including the geographical location of the subjects, exposure of lack of exposure to allergens throughout their lives, hereditary differences, etc.  It would be nearly impossible to control for all these factors and be able to say definitively that a C-section delivery is responsible for allergies later in life.

• What is the mechanism?

Understanding the mechanism plays very intimately into the first two questions brought up here. If we understood the mechanisms of the interactions between microbiomes and human disease as well as human neuropsychology, the problems of causation, correlation, and the cloaking of important genes by other dominant gene sequences would be much less of an issue.  

• How much do experiments reflect reality?

Many experiments involving microbiome research rely on germ free mice.  Also laboratory methodology often doesn’t reflect relevant situations in real life. The author argues that this is a weakness.  I think it can be if conclusions are made that are out of context with real life situations.  However, I think these experiments are vital to further progress knowledge in this area. I think of them more like pilot studies that give us information to work with to make more creative experiments with better controls for more realistic implications.

• Could anything else explain the results?

Clearly, with any scientific experiment, methodology and data, researchers must take into account the possibility of other factors explaining the results.  A good experiment and sound scientific research must include controls in the methodology.  Medical research does have a history of making erroneous conclusions based on conjecture that have affected many people in a negative way.  I feel like a warning by the author about this is definitely appropriate because there is so much still unknown about the cause and effect relationships between the microbiomes and their effects on the human condition. 

I think the most important and helpful question  to look at when discussing this controversy is the question regarding the biochemical and organic mechanisms involved in our symbiotic relationship with microbiomes. Once we understand the mechanisms better, it will help clear up our understanding of causal relationships in some cases, which will then help us understand the results of experiments, will help identify causal relations and correlations, and help us conjecture possible identification of functional groups and gene sequences involved in the mechanisms overall.