It is Aristotle that once famously remarked how “man is by nature a social animal”. Of course, we need only reflect on our past experiences for a short while to understand the truth in Aristotle’s words. Our very existence as a species depended on our ancestor’s abilities to interact and help one another. Seeing as how social skills often (but not universally) serve as a prerequisite for a fulfilled life, social psychologists and neuroscientists alike have dedicated large resources to deciphering the mechanisms behind our social nature. A major breakthrough came at the turn of the 20th century, when Henry Dale discovered “Oxytocin”, a chemical that has earned the reputation of the “love hormone” for its role in encouraging social bonding, prosocial behaviours, “maternal instincts”, fear reduction and in antagonizing the effects of depression (learn more here: 1). But oxytocin alone cannot explain the entirety of our social behaviour.
We’re missing something.
In natural sciences, one will often hear the phrase “paradigm shift” to describe a series of scientific findings that radically alters our basic understanding of a scientific phenomenon (the most notable example, for instance, is Charles Darwin’s Evolutionary Theory, which rigorously challenged the way in which we perceived our very origin as a species). With a wealth of studies demonstrating new ways in which our intestinal bacteria dictates our health and behaviour (a great review can be found here: 2), the gut microbiome is primed to give way to the next great paradigm shift – particularly in relation to the extent to which the gut-brain axis influences our mood and behaviour.
If you are familiar with my previous blog post Life on The Spectrum – An Abnormal Microbiome and…Autism?, you may recall the three characteristic behavioural autism-like symptoms: limited social interactions, a tendency for repetitive behaviour and reduced overall communication (3). Autism patients are also known to possess an altered gut microbiome composition (4). Up until recently, this observation was merely an association; an altered gut microbiome in autistic patients was associated with disruption in social development, but was never shown to be a cause of social disruption. However, recent evidence emerging from the lab of Dr. JF Cryan at University College Cork in Ireland (5) suggests that an altered gut microbiome does indeed impede normal social development.
To support his claim, Cryan’s team studied the social behaviour of mice using a “three-chambered sociability test” (6). This test includes a three-chambered box with openings between the chambers. In brief, this setup assesses social behavior in the form of general sociability as well as interest in social novelty. Cryan’s group performed two experiments:
The results of this study have potentially large implications in the realm of autism. In addition to symptoms of reduced social motivation, children with autism exhibit poor communication skills as well as repetitive behaviours. Since it is well understood that many autism patients have a dysregulated gut microbiome, is it a far-stretched hypothesis that the impaired social behaviour observed among autistic patients is at least a partial result of an abnormal microbiome? If so, could we substantially decrease autism-like symptoms and increase social development by focusing our treatments and efforts on re-balancing the gut microbiome?
And how about introverts? Approximately 50% of the population identify themselves as introverted (7). Do they house a microbiome that differs from those of extroverts? Cryan’s results spur a whole new set of questions concerning our social behaviour as a species.
A final question that may come to mind is why gut bacteria are dictating our social behaviour. We have a fairly clear idea as to how – via the gut-brain axis. But why have humans and microbes co-evolved in such a way? Although we cannot know for certain, it is worth noting that microbes have lived on Earth for far longer than humans have. In that time, microbes have yearned for one ultimate evolutionary goal: to reproduce and spread throughout the planet. Is it possible, then, that bacteria, in a parasitic way, are purposefully encouraging our social drive? By encouraging us to interact with other humans, bacteria can jump to our neighbors, who then go their own way. Just like that, bacteria figured out a way long ago to use mammals as vehicles to spread across the globe… Although this idea is difficult to prove, what a remarkable mechanism that would be – microbes stimulate our social development for their benefit, to promote their spread.
And if that’s true, what other behaviours are being manipulated by microscopic organisms? If our gut microbiome is controlling our social development, who’s to say they don’t play a role in other cognitive functions? Are we really in control of our own thoughts and actions, or are we merely the puppets in a microbe-dominated world?
1. Ishak, W. W., M. Kahloon, and H. Fakhry. 2011. Oxytocin role in enhancing well-being: a literature review. J. Affect. Disord. 130: 1-9.
2. Shreiner, A. B., J. Y. Kao, and V. B. Young. 2015. The gut microbiome in health and in disease. Current opinion in gastroenterology 31: 69-75.
3. Prevention, C. f. D. C. a. 2012. Autism Spectrum Disorder — Data & Statistics.
4. Kang, D. W., J. B. Adams, A. C. Gregory, T. Borody, L. Chittick, A. Fasano, A. Khoruts, E. Geis, J. Maldonado, S. McDonough-Means, E. L. Pollard, S. Roux, M. J. Sadowsky, K. S. Lipson, M. B. Sullivan, J. G. Caporaso, and R. Krajmalnik-Brown. 2017. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 5: 10.
5. Desbonnet, L., G. Clarke, F. Shanahan, T. G. Dinan, and J. F. Cryan. 2014. Microbiota is essential for social development in the mouse. Mol. Psychiatry 19: 146-148.
6. Yang, M., J. L. Silverman, and J. N. Crawley. 2011. Automated three-chambered social approach task for mice. Curr. Protoc. Neurosci. Chapter 8: Unit 8.26.
7. Myers, I. B., McCaulley, M. H., Quenk, N. L., & Hammer, A. L. (1998). MBTI Manual: A guide to the development and use of the Myers-Briggs Type Indicator (3rd ed.). Palo Alto, CA: Consulting Psychologists Press.
An alternative look at the gut microbiome
So far, we’ve have the pleasure of introducing you to various aspects of the gut microbiome through an amazing range of articles like Reginold Sivarajan’s “A Cure for Alzheimer's Disease?”; Adam Hassan’s “Pregnancy and the Gut Microbiota”; and Mario Corrado’s ““Losing Track of Time” — How Gut Bacteria’s Daily Routine Impacts Our Health”. Today we’d like to present a different but equally exciting aspect of this field: modifying the gut microbiome of mosquitos to fight tropical diseases.
Malaria is a vector-borne parasitic disease endemic to South America and sub-Saharan Africa. Its vector are mosquitos in the genus Anopheles, many species of which thrive in these regions. The disease burden associated with malaria is huge and horrific: it caused 445,000 deaths worldwide in 2016, 90% of which were in Africa. (World Health Organization, 2016) As such, a substantial amount of funding is dedicated to fighting this disease compared to others—worldwide, in 2016, “US$2.7bn were allocated for malaria control and elimination efforts”. (World Health Organization, 2017) Though this is short of the investment required if internationally negotiated goals are to be met, this pool of funding still allows for the development of creative approaches to malaria control.
Enter the gut microbiome. The 2010s have seen an explosion in the popularity of microbiome research, especially centred around the role of the gut microbiome. As we near 2020, it is clearly apparent that this trend is not about to change: the Canadian government is blazing a trail with its Canadian Microbiome Initiative; in parallel, the Obama administration announced the US National Microbiome Initiative [archive link], though no documents have been released since 2016 and the link is currently broken.
So how does the microbiome tie into malaria control? The idea is a brilliant application of gut microbiome research: seed the gut of mosquitos specifically with deleterious bacteria. Bacteria in the genus Wolbachia infect insects. They have two unique abilities when infecting mosquitos: firstly, they induce “cytoplasmic incompatibility” between male and female Anopheles mosquitos. (Sinkins, 2004) The mechanisms governing this are as yet unclear. However, what this means in practice is the following: if an infected male mates with an uninfected female, the offspring die before even being born. This reduces the overall number of mosquitos born, which is useful. Infected females can mate with uninfected males; however, the offspring will also be infected. Thus, the whole population can be infected very rapidly by simply releasing large quantities of infected females!
The second amazing ability that Wolbachia bacteria have is that they shorten the lifespan of the mosquitos they infect. (Schraiber et al., 2012) A shorter life span for the vector means less time for the malaria parasite to be transferred! As mentioned, all that needs to be done to ensure that the whole of a local population is infected (and therefore short-lived) is to release infected females periodically.
An Australian study (focused on dengue-spreading mosquitos), did just this. Dengue is another tropical disease spread by Anopheles genus mosquitos, which also has a serious disease burden in tropical regions. In this study, 100% of the local mosquito population was found to be infected after 9 releases of infected females spaced 10 days apart. In just three months, the whole of the mosquito population’s gut microbiomes had been modified, reducing their lifespan and hindering the spread of dengue. (Hoffmann et al., 2011)
What other effects can we obtain by adding other bacterial species to this vector—or others? How many more easily exploitable solutions are there to disease control, waiting to be discovered until governments & funding bodies recognise the vital importance of infectious disease research?
Reaching a better understanding of the mosquito gut microbiome and its contributions in the normal host life cycle falls squarely into the category of research that receives the least funding: “basic” or “fundamental” research. At what cost are we delaying funding research into the basic sciences? Considering the number of diseases spread through mosquitos in particular, and the huge proportion of morbidity and mortality that they account for in tropical regions, it seems plain that we cannot afford to delay for much longer.
Hoffmann, A. A., B. L. Montgomery, J. Popovici, I. Iturbe-Ormaetxe, P. H. Johnson, F. Muzzi, M. Greenfield, et al. 2011. “Successful Establishment of Wolbachia in Aedes Populations to Suppress Dengue Transmission.” Nature 476 (7361): 454–59. doi:10.1038/nature10356.
Schraiber, Joshua G., Angela N. Kaczmarczyk, Ricky Kwok, Miran Park, Rachel Silverstein, Florentine U. Rutaganira, Taruna Aggarwal, et al. 2012. “Constraints on the Use of Lifespan-Shortening Wolbachia to Control Dengue Fever.” Journal of Theoretical Biology 297: 26–32. doi:10.1016/j.jtbi.2011.12.006.
Sinkins, Steven P. 2004. “Wolbachia and Cytoplasmic Incompatibility in Mosquitoes.” In Insect Biochemistry and Molecular Biology, 34:723–29. doi:10.1016/j.ibmb.2004.03.025.
World Health Organization. 2016. “World Malaria Report 2016.” World Health Organization. doi:10.1071/EC12504.
World Health Organization. 2017. “World Malaria Report 2017.” World Health. doi:ISBN 978 92 4 1564403.
Most of you likely know someone or will know someone who has type 2 diabetes. Not only does it account for around 90% of all diabetes, it affects around 8% of the world’s population. When you have type 2 diabetes, your body essentially does not recognize insulin, the protein that tells the cells in your body to take up glucose from your blood. Your cells don’t get enough sugar and cannot function properly. Furthermore, all that extra glucose floating around in your blood can also have devastating effects.
Its prevalence has been increasing, along with the rising obesity epidemic. This is because obesity and similar diet and lifestyle choices often cause type 2 diabetes. There are other causes, such as genetics, gender, and certain bacteria in the gut microbiota as well. The bacterial species Bacteroides and Prevotella have been connected with type 2 diabetes, and this is important for a study that was recently done with medication for type 2 diabetes.
The medications used in the study were Glipizide, which acts by trying to ramp up your body’s insulin production, and Acarbose, which stops more complex sugars from being broken down thus making sure less glucose is absorbed into your blood. While Glipizide would have no effect on the bacteria in the users gut, Acarbose would allow more complex sugars to pass farther into the intestine and thus provide different molecules for bacteria to chow down on. This key difference was vital for explaining the effects the researchers saw.
Patients treated with acarbose had increased amount of Lactobacillus and Bifidobacterium, and depleted amounts of Bacteroides. Clearly Bacteroides aren’t that big of a fan of those new complex sugars. This change in bacterial composition clearly also changed the genes involved in bile acid metabolism. This is important because specific types and ratios of bile acids are heavily involved in metabolism. The change in genes, changed the amount and type of bile acids present in the patients. This change provided the patients with a lot of benefits, including lower blood sugar and increased responsiveness to insulin.
The researchers also noticed that within the group of patients treated with Acarbose, those with a higher level of Bacteroides than Prevotella exhibited greater improvement of metabolic parameters, and thus lowered the burden of type 2 diabetes. These findings could potentially show that knowledge of a the bacteria swimming around in a type 2 diabetic’s gut would allow the prediction of which medication would have a greater affect on them.