Intestinal Parasites: It's a No Guts, No Glory Situation

A topic that makes most of us squirm - intestinal parasites. Those pesky little things that make it their business to live, rent-free, inside of us.?

You might think of intestinal parasites as unusual things affecting unlucky travellers or pets, or you might think of them as somewhat exotic creatures. But they’re nowhere near as uncommon as you might believe them to be.

In this blog, you’ll learn about some of the most common intestinal parasites and how they get away with their Machiavellian, parasitic feats.?

The facts about intestinal parasitic infections

Intestinal parasites can be broadly split into two main groups: helminths and protozoa.?

Helminths are often much larger than protozoa. As multicellular parasites, they cause a range of health problems depending on the type of worm. Some, like tapeworms, can cause weight loss and malnutrition. Protozoa, on the other hand, are single-celled, much smaller, and often cause more acute symptoms such as diarrhoea, nausea, and stomach cramps.

While intestinal parasitic infections (IPIs) rarely directly lead to death, the effects of parasitic burden on susceptible individuals can be devastating. In children, IPIs are correlated with severe stunting and wasting, which itself can disrupt the immune system - leading to a vicious cycle if not treated rapidly [1].?

The true number of cases is difficult to quantify due to factors such as asymptomatic infections, variable diagnostic methods, regional differences in prevalence, and challenges in data collection. Despite this, estimates suggest somewhere in the region of 3.5 billion people are affected worldwide [2]. Of course, hygiene has improved significantly over the past few decades meaning IPIs have also declined. But in some areas of the globe, they still cause a huge burden on people and healthcare systems. In fact, of those 3.5 billion people, around 450 million have active symptoms.?

Let that sink in.??That’s 450 million people with symptoms ranging from mild to debilitating and sometimes deadly symptoms, such as:

●??????Abdominal pain

●??????Diarrhoea

●??????Nausea or vomiting

●??????Gas or bloating

●??????Dysentery (loose stools containing blood and mucus)

●??????Stomach pain or tenderness

●??????Lethargy

But what about those without symptoms? How do parasites survive in humans without causing collateral damage? There are likely many factors involved including age, gender, comorbidities, and genetic predisposition. However, there’s one more factor that we haven’t yet introduced.

Put simply, intestinal parasites manipulate our immune systems to survive. In fact, they are quite adept at it. They are masters of disguise capable of tricking or hijacking our immune system to exploit us for their own survival.

While I don't want to oversimplify the topic of human immune responses, for the purposes of this blog, I will do just that.?

Without further ado, let’s get started…

Giardia intestinalis:?Tiny, yet tenacious

Ah, Giardia. A parasite that has a knack for surviving in harsh environments. It's no wonder it's one of the most common intestinal parasites in the world.

But how does this little pest survive inside our bodies? Well, for starters, it has a unique shape that allows it to attach to the lining of our intestines like a suction cup. From there, it feeds on the nutrients in our digestive system and reproduces at an alarming rate. And if that wasn't enough, it also can form a protective coating around itself, making it even harder for our immune system to detect and attack it.

Giardia intestinalis (G. intestinalis) may be small, but it's mighty when manipulating our immune system. Studies have shown that the parasite can alter the way our immune system responds to infections, making it harder for our bodies to fight off other pathogens.

One way?G. intestinalis?does this is by disrupting the balance of bacteria in our gut microbiome. Our gut is home to trillions of bacteria that play a crucial role in regulating our immune system. When?G. intestinalis?infects the intestines, it can disrupt this delicate balance, leading to an overgrowth of harmful bacteria and a decrease in beneficial bacteria.

Giardia also produces a protein that can directly interfere with our immune system's ability to recognise and attack other pathogens. This protein modulates a master regulator of immune responses, known as NF-κB, to inhibit the production of pathogen-munching macrophages [3].

Entamoeba histolytica: A Z-list celebrity

Entamoeba histolytica?(E. histolytica) may not be as well-known as some other intestinal parasites, but it's certainly no less concerning. Causing around 100,000 deaths per year, this tiny creature can cause many health problems, from mild digestive issues to severe inflammation and even organ damage [4]. And, while it's often found in developing countries where sanitation and hygiene are poor, it's important to remember that anyone and anywhere can become infected.

What's particularly concerning about?E. histolytica?is its ability to manipulate our immune system, but not before causing significant damage to your gut. By breaking down our intestinal cells, it wreaks havoc, triggering a strong immune response. But this parasite doesn't stop there. It also produces a range of proteins that can directly interfere with our immune response.?

Perhaps the most insidious way that?E. histolytica?modulates our immune system is through its impact on our gut microbiome.?E. histolytica?eats friendly bacteria for breakfast, lunch, and dinner, promoting the growth of harmful bacteria to tip the delicate balance in their favour. This can have a long-lasting impact on our health and immune function, even after the infection is cleared.

Ascaris lumbricoides: Bigger, but not better

Ascaris lumbricoides (A. lumbricoides), or the giant roundworm, is a common intestinal parasite that infects millions of people worldwide. Growing up to a foot long,?A. lumbricoides?lives in the intestines, feeding on the host's nutrients and causing symptoms, including abdominal pain, diarrhoea, and vomiting.?

Want to hear something incredibly gruesome? Once?A. lumbricoides?larvae migrate to the lung, they’re coughed up and swallowed allowing them to re-enter the gut, mature into adult worms and start the whole cycle again.?

But that's not all they do.

In the lungs,?A. lumbricoides?larvae can induce an immune response associated with allergic and inflammatory disorders and may contribute to the development of asthma and other allergies [5].?

Trichinella Spiralis -?A personal favourite

Let's finish off with my favourite parasite of all time. Yes, I have a favourite and it’s a wriggly roundworm.

Meet?Trichinella spiralis (T. spiralis), your friendly pork parasite. Not the most dangerous by any stretch. But one of the most interesting.?

T. spiralis?causes trichinosis and is found in undercooked meat, particularly pork. Once ingested and exposed to the low pH of the stomach, larvae are released where they travel through the digestive system, eventually maturing into adult worms. Larvae released here migrate to striated muscle, forming cysts while they wait for the next host to eat them.?

What is most interesting about this intestinal parasite is that when it forms cysts within the muscle tissue, it can switch off some human immune responses for an incredibly prolonged period - in some cases, residing in human muscle tissue for over a decade.

T. spiralis?has numerous secret weapons. I’d go so far as to say, an arsenal of weapons, to evade human immune responses. Like many proteins involved in immune responses,?T. spiralis?weapons are complex and multifaceted and will depend on the surrounding environment and stage of the life cycle. Some proteins secreted by?T. spiralis?mimic human immuno-modulatory proteins and chemical messengers [6]. Combined with the fact that?T. spiralis?adapts the protein profile depending on the local environment, it becomes easy to see how it might offer a huge advantage within the intestinal environment.?

Insights from Intestinal Parasites

So, the little critters that live in our gut are way more intelligent than we once thought and have evolved complex ways of manipulating our immune system to survive and thrive in the human body. But fear not. The more we learn about these parasites and their immune-modulating strategies, the better equipped we are to fight back and develop treatments to clear them.

Not only can studying these parasites help us fight them off, but it can also give us insights into our immune system. By understanding how parasites manipulate our immune responses, we can learn about the intricate mechanisms that regulate our immune system and maintain its balance. And this knowledge could potentially help us treat diseases, such as autoimmune disorders, where our immune system attacks our cells by mistake.

Here are some questions we should be asking:

• How do interactions between different types of parasites and the gut microbiome affect the immune system and overall health?
• What is the impact of co-infections with multiple parasite species on immune responses and disease outcomes?
• What are the long-term effects of chronic parasitic infections on immune function and overall health, including potential links to chronic diseases such as cancer and autoimmune disorders?
• Can immune modulation by parasites be used as a therapeutic strategy for autoimmune diseases and other immune-related disorders?
• What are the potential risks and benefits of using immune modulation by parasites as a therapeutic strategy?

To conclude, let's not underestimate the power of these tiny parasites that live in our gut. They may seem like a nuisance, but they hold valuable lessons for our understanding of the human immune system. Who would have thought that such small creatures could teach us so much?

References

• Fauziah N, Aviani JK, Agrianfanny YN, Fatimah SN. Intestinal Parasitic Infection and Nutritional Status in Children under Five Years Old: A Systematic Review. Trop Med Infect Dis. 2022 Nov 12;7(11):371. https://doi.org/10.3390/tropicalmed7110371
• Hotez, P. J., Fenwick, A., Savioli, L., & Molyneux, D. H. (2009). Rescuing the bottom billion through control of neglected tropical diseases. Lancet (London, England), 373(9674), 1570–1575.?https://doi.org/10.1016/S0140-6736(09)60233-6
• Faria CP, Neves BM, Louren?o á, Cruz MT, Martins JD, Silva A, Pereira S, Sousa MDC. Giardia lamblia Decreases NF-κB p65RelA Protein Levels and Modulates LPS-Induced Pro-Inflammatory Response in Macrophages. Sci Rep. 2020 Apr 10;10(1):6234. https://doi.org/10.1038/s41598-020-63231-0
• Bercu, T. E., Petri, W. A., & Behm, J. W. (2007). Amebic colitis: new insights into pathogenesis and treatment. Current gastroenterology reports, 9(5), 429–433.?https://doi.org/10.1007/s11894-007-0054-8
• Midha A, Ebner F, Schlosser-Brandenburg J, Rausch S, Hartmann S. Trilateral Relationship: Ascaris, Microbiota, and Host Cells. Trends in Parasitology. 2021;37(3):251-262. doi:https://doi.org/10.1016/j.pt.2020.09.002
• Bruschi F, Ashour DS, Othman AA. Trichinella-induced immunomodulation: Another tale of helminth success. Food Waterborne Parasitol. 2022 May 16;27:e00164. doi:?https://doi.org/10.1016/j.fawpar.2022.e00164?????