microbiome gastrointestinal track

Microbiome Therapies – Just Go with Your Gut

Influence of the Microbiome


By Ryan Mateja, PhD

There are about 500-1000 different species of intestinal microbiota, comprising a total of approximately 100 trillion microbiota in the human intestine.1 These microbes make up your own personal microbiome, and science is quickly learning that the microbiome can influence nearly every part of the human body, even the brain.

For example, toxoplasmosis causes rodents to be more active, less fearful overall and specifically less fearful of the odor of cat urine, a fear which non-infected rodents possess.2 What benefit does this behavior provide to Toxoplasma gondii, the microorganism that causes toxoplasmosis? Well, Toxoplasma gondii reproduce in the intestines of felines and are shed in their feces. Therefore, altering the way rodents act towards such a predator will serve to increase the rodent’s odds of being preyed upon and ultimately consumed by the feline. As such, this evolutionary adaptation increases the chances that the Toxoplasma gondii will continue to reproduce, essentially making their way from the ground back into another feline.

Can a similar phenomenon occur in humans? Well, you are most likely already aware of one such instance in the form of the rabies virus. The rabies virus has many neurological effects such as anxiety, paralysis, hallucinations and even hydrophobia (the fear of water). It is thought that hydrophobia causes the infected person to have an increase in salivation, and since the rabies virus aggregates in the salivary glands this increases the chances of transmission to others.3

100 trillion

Number of microbiota cells in the human intestine

Neurological Effects of Manipulating the Microbiome

In fact, it is now thought that the microbiome plays a role in many neurological conditions such as obsessive compulsive disorder and autism; and also emotions like anxiety, aggression and sadness.4 Therefore, an understanding of the vast influence the microbiome has will undoubtedly open up new and exciting opportunities to diagnose and treat patients.

99 %

Percent of the microbiome housed in a digestive tract

Multiple pioneering studies have shown that probiotic consumption can influence the processing of emotion in humans, whether measured by differences in activity in the region of the brain involved with emotional processing using fMRI5 or by using self-reported feelings of sadness, aggressive thoughts, or anxiety.6,7 Now knowing that the microbiome can measurably alter emotions, scientists are eagerly looking at the relationship between the microbiome and more severe neurological conditions.

microbiome gastrointestinal track

This is how we imagine the microbiota residing in the human gastrointestinal track. If your research focuses on microbiome-related therapies, consider our digital design services to visualize your science!

Recently, there has been interest in looking at the connection between the microbiome and autism spectrum disorder (ASD). The suggestion that a connection exists between the microbiome and ASD stems from the observation that many children with ASD suffer from increased inflammatory bowel disease and other gastrointestinal (GI) disorders compared to neurotypical children.8 Furthermore, studies have shown that the extent of GI dysfunction and severity of ASD exhibited are strongly correlated.9 Stronger evidence comes from a recent small open-label clinical trial which examined the impact of a 7-8 week long Microbiota Transfer Therapy (MTT) on GI and ASD symptoms.10 ASD-diagnosed children went through a two-week antibiotic treatment and a bowel cleanse followed by a fecal microbiota transplant course to re-populate their gut microbiota using a standardized source prepared from healthy individuals. Following the MMT the children showed significant improvements in both GI and ASD related symptoms, which persisted for at least 8 weeks after treatment ended. Looking at the microbiota composition of the children with ASD, the MMT shifted their microbiota to be more similar to that of neurotypical children. These findings support the idea that microbiota play a significant role in ASD symptoms.

The Microbiome as a Future Drug Delivery System

Pushing the boundaries even further, synthetic biologists are working to engineer bacteria and mammalian cells so the cells themselves are able treat certain diseases and act as therapeutic agents or “living pills.”11 For instance, scientists have already engineered a cell to be a “biomedical biosensor” which can detect a flare-up of the skin disease psoriasis and respond by releasing anti-inflammatory cytokines to sooth inflammation and provide on-the-spot treatment.12 Another area of research involves using the academic information obtained from studies on the microbiome to influence the interplay between our microbiota, the immune system and a the mechanism of action of disease to create a therapeutic bacterial cocktail. This bacterial cocktail would contain specifically selected commensal microbial species in order to remodel the gut microbiome and treat the disease.13 One major concern of modulating the microbiome is the importance of looking for unintentional global effects as much or even more than focusing on the intended ones. This is similar to the concerns mentioned in a previous article discussing editing genes with the CRISPR-Cas9 system; when dealing with influencing large scale complex systems like the microbiome or genome, minimizing uncertainties is paramount

It appears as if the future of neuroscience might hinge on discoveries made about the microbiome, an organ whose complexity and influence is finally becoming understood. Knowing this brings a new depth to the common adage uttered when faced with a perplexing dilemma, “Just go with your gut.”

$300

Projected worldwide market for products that leverage the human microbiome in millions, by 2019


References:
1. Kamada N, Seo SU, Chen GY, Núñez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013 May;13(5):321-35.
2. Dubey JP, Lindsay DS, Speer CA. Structures of Toxoplasma gondii tachyzoites, bradyzoites, and sporozoites and biology and development of tissue cysts. Clin Microbiol Rev. 1998 Apr;11(2):267-99.
3. Rabies. (2017, February 12). In Wikipedia, The Free Encyclopedia. Retrieved February 12, 2017, from https://en.wikipedia.org/w/index.php?title=Rabies&oldid=765088812
4. Gonzalez A, Stombaugh J, Lozupone C, Turnbaugh PJ, Gordon JI, Knight R. The mind-body-microbial continuum. Dialogues Clin Neurosci 13(1):55-62, 2011.
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7. Messaoudi M, Lalonde R, Violle N, et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects. The British journal of nutrition. 2011; 105:755–764.
8. Kohane IS, McMurry A, Weber G, et al. The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS One. 2012;7(4):e33224.
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10. Kang DW, Adams JB, Gregory AC, et al. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017 Jan 23;5(1):10.
11. Eisenstein M. Living factories of the future. Nature. 2016 Mar 17;531(7594):401-3.
12. Schukur L, Geering B, Charpin-El Hamri G, Fussenegger M. Implantable synthetic cytokine converter cells with AND-gate logic treat experimental psoriasis. Sci Transl Med. 2015 Dec 16;7(318):318ra201.
13. Jarvis LM. Harnessing the hordes in the microbiome. Chem Eng News. 2015;93(38):12–19.