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.
Early Bird Gets the Worm… But Does It Want that Worm? – How Your Gut Deals with Intestinal Parasites
Neglected tropical diseases (NTDs) refer to tropical diseases which affect low-income countries primarily in Africa, Asia, the Middle East and South America. These diseases are thought of as “neglected” due to them receiving less financial support in terms of research funding and treatment. Everyone has heard of HIV/AIDS, malaria, and tuberculosis. However, how many of you know about schistosomiasis, chikungunya fever or leishmaniasis? Causative agents of this group of diseases include viruses, bacteria or parasites (protozoa and helminths).
Of course, most of the money and resources are in developed regions (i.e. North America and Europe). Thus, there is less incentive to invest in the treatment and prevention of NTDs if the “home” population is not directly or primarily affected. When it comes to viruses and bacteria, a lot of progress has been made. However, there are still no vaccines available for parasitic infections. You may want to remember that the next time you travel! (Disclaimer: many NTDs are treatable and it is very important to visit your travel clinic.)
So, how do parasites affect our gut..? Well, there are several intestinal parasitic infections such as giardiasis, ascariasis, and strongyloidiasis. These parasites, often worms in the adult stage, infect your gastro-intestinal tract by the ingestion of infected food or water, the fecal-oral route, or by skin absorption. The main populations affected are actually children with the World Health Organization (WHO) estimating that number to be around 880 million (1). It is important to note that a parasite’s first instinct is not to kill you. A parasite wants to live with you as it needs you for nutrients (hence why it is called a “parasite”). Complications from how our bodies react to this unwelcomed squatter often lead to severe symptoms down the road and eventually death if left untreated for many years.
We have covered at great lengths in previous blog posts how complex our gut microbiota is and how the notion of balance is very important. Well, most of us would say that the presence of worms in your intestine does not quite qualify as “normal”. When parasites enter your system and mature, they interact with your gut microbiota. Often, the host’s resident gut microbiota is able to interfere with the parasite and undermine it (2). In fact, the bacteria are there to line your gut and to prevent any other microorganisms from invading and establishing itself. But behold, the parasite can also create a more favourable environment for itself. Many protozoans and helminths can secrete molecules that will affect the state of balance in our guts so that they can establish themselves within us. On top of that, parasites live with their host and profit from the nutrients that are being degraded in the intestine as well (2).
The interactions between our gut bacteria and invading parasites are quite complex. Mouse models have shown that the same, normal gut microbiota can protect against some parasites such as Cryptosporidum but cause you to also be susceptible to other species (3,4). Interestingly, probiotics have been found to be effective against several species of parasites. So, on top of helping with gastrointestinal disorders, they play a role in stopping the development of these organisms (5). Something to remember the next time you’re eating your yogurt!
Finally, this leads us to the idea of modulating/altering your gut microbiota. Homeostasis is a key concept. If a parasitic organism disturbs this balance, you can restore it by introducing probiotics as mentioned above. Some species of probiotics include Lactobacilli and Bifidobacteria species. Administration of probiotics leads to a boost in the immune system. This can be observed by a growing number of immune cells (such as T cells) and IgA antibodies, which will act against the invading pathogen (6). Not only is it possible to stop the development of pathogens, it is also possible to help in your recovery if infected!