FIRST, WHAT IS THE MICROBIOME?
Microbiota: a more general term for all the microorganisms that live in a particular environment
Microbiome: the entire collection of genes found in all the microbes associated with a particular host
Metagenome: genetic material from a mixed community of organisms
Metatranscriptome: sum total of all messenger RNA expressed by a group of interacting organisms
*Although the microbiome is not a new phenomenon, it continues to gain popularity and attention, with an exponentially increasing number of publications each year.
A big reason for this is the advent of new technology: we can now apply whole genome sequencing to bacteria as opposed to cell cultures:
DYSBIOSIS OF THE MICROBIOME AND DISEASE
Dysbiosis has been identified to occur in a huge number of health conditions, including anorexia, Parkinson’s disease, and even spinal cord injury!
But, as any scientist knows, correlation is not causation. It has yet to be proven that the occurrence of dysbiosis is producing these diseases, and not a result of the disease or some third confounding variable.
Furthermore, What is Dysbiosis really?
There are approximately 6 phyla found in the gut:
•Bacteroidetes •Firmicutes •Actinobacteria
•Proteobacteria•Verrucomicrobria •Fusobacteria
Defining dysbiosis is difficult, because there is such variability in microbiota between individuals. We are not really able to define what a “healthy microbiota” is either. Saying that dysbiosis is a change in the gut microbiota composition, or reduction in the microbiota diversity is very simplified. For example, we need bacteria to produce the metabolite butyrate. However there are many bacteria that produce butyrate. You can have two individuals producing a healthy level of butyrate, but one has 8 butyrate producers, while the other has only one.
As seen above, these two pediatric populations have vastly different microbial compositions, which De Filippo et al. propose has occurred from their vastly different diets. The Florence population has a diet very similar to the western diet, and has a microbiome with reduced richness and biodiversity. However, at the end of the day, both populations are still healthy kids.
Confounders - the scientist's arch nemesis
There are many examples that illustrate the uncertainty regarding what we know about the gut microbiota and it’s effects on disease. One study can propose that artificial sweeteners can induce glucose intolerance and contribute to diabetes by changing the microbiota2. Then another can provide evidence against the association between microbiome changes and diabetes by showing that a medication for the disease (metformin) is causing both3.
CHALLENGES IN MICROBIOME STUDIES:
Technical and contamination issues are rampant in the microbiome literature.
As an example, in the figure above, you can see the sequencing results from a 16S rRNA taxonomic assignment, starting with a pure cultured sample. At first the result appears to be one species, but through a series of ten-fold dilutions, the contamination increases exponentially. In the end the three different sites each have a different result. It has also been shown that contamination is kit dependent, and using 4 different kits obtained 4 different contamination profiles.
Other problems with human studies include: confounded age, geographic locations, lifestyles, diets, host genetics. Also: lack of standardization (sampling, extraction, processing, sequencing, analyzing) and batch effects—technical sources of variation. For example, having so many samples, that they can’t all be labelled at the same time point.
SO CAN WE CHANGE OUR MICRBIOBIOMES TO CURE/IMPROVE DISEASE?
Diet intervention? Diet trials have been unsuccessful, but perhaps because they are only modifying one component of the diet. In addition, the diet of a host is significant, and although giving a supplement daily may not work, perhaps pulsing a specific nutrient to encourage growth of a certain bacteria can help.
What about yogurt or probiotics? Many probiotics are made to get through stomach acid – they are selected for that reason, rather than for their function. Therefore they may not work unless you have all the correct bacteria to produce the end results.
What about fecal microbial transplant (FMT)? FMT has been shown to be very beneficial to treat recurrent Clostridium Difficile infection. However, it has not been as successful in IBD patients. This may be because IBD patients have underlying genetic defects that drive towards a certain microbiome. Repeated FMT may be needed to affect the microbiome.
TAKE HOME MESSAGE:
The future is still bright for microbiome research, and it is definitely still an important player in a variety of diseases. However, the extent of the microbiome’s impact on our health has been exaggerated and glorified by the media, and there are still many uncertainties and challenges that line the road ahead for scientists in this field.
Image taken from blogspot.com
REFERENCES:
Filippo, C. D., Cavalieri, D., Paola, M. D., Ramazzotti, M., Poullet, J. B., Massart, S., . . . Lionetti, P. (2010). Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proceedings of the National Academy of Sciences, 107(33), 14691-14696.
Suez, J., Korem, T., Zeevi, D., Zilberman-Schapira, G., Thaiss, C. A., Maza, O., . . . Elinav, E. (2015). Artificial Sweeteners Induce Glucose Intolerance by Altering the Gut Microbiota. Obstetrical & Gynecological Survey, 70(1), 31-32.
Forslund, K., Hildebrand, F., Nielsen, T., Falony, G., Chatelier, E. L., Sunagawa, S., . . . Pedersen, O. (2015). Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature, 528(7581), 262-266.
Lees, C. W., Barrett, J. C., Parkes, M., & Satsangi, J. (2011). New IBD genetics: Common pathways with other diseases. Gut, 60(12), 1739-1753.