Our gut is colonized by trillions of microorganisms, including bacteria, that are essential for the proper functioning of our digestive and immune systems. While we co-exist peacefully with most microbes, harmful bacteria or pathogens can at times proliferate in our gut and make us sick. The distinction between good and bad can sometimes become blurred however, as under certain conditions some typically beneficial microbes can become harmful and cause disease. We invite you to imagine our gut as a battlefield where bacteria fight for survival, and the outcome of the battle determines whether we stay healthy or become ill.
This article was co-written by Léa Swistak
1) The good: How are good bacteria (known as commensals) essential for our well-being?
Our gut contains a larger number of bacterial cells than human cells, so how and why do we tolerate such foreign colonization? What do bacteria do for us? As cellular microbiologists, we are puzzled by these questions and if you have read this far, the chances are you are too. We certainly do not know all the answers, and researchers worldwide are currently investigating these questions, but here is what we do know:
Nutrition: Good bacteria (or commensals) that live in our gut play an important role in our nutrition. Some synthesise essential vitamins that humans cannot produce and others secrete enzymes to break down the food we ingest into molecules our cells can absorb.
Protection: We need these commensals to protect us from harmful bacteria by simply occupying the territory. Their presence will use up the local resources and safeguard the gut from pathogens. In addition, commensals have defence mechanisms to fight other bacteria. For example, they can secrete antimicrobial substances that kill or prevent the proliferation of competing bacteria. Therefore, territory battles in our gut are constantly raging as new bacteria pass through our digestive system.
Immunity: Commensals are a powerful ally to our immune system, as they train our cells to specifically recognize and kill pathogens. By interacting with a vast and diverse range of microbes in the gut, our immune system learns which harmful bacteria to attack and which beneficial bacteria to leave alone.
Altogether, our good bacteria help us live in peace while they act like a foreign legion, protecting their host.
But are all bacteria good? Of course not! A small minority of our microbiome, also known as flora, is made up of powerful enemies which wage epic battles, occasionally succeeding, and ultimately causing disease.
2) The bad: How do pathogens invade our gut?
What makes some bacteria bad, and how do they win against our strong military forces of immunity and commensals? A bacterium is classified as bad or pathogenic if it can cause disease. Keep in mind though, the life purpose of any bacterium is the same as any other microorganism: replicate and spread. Making us sick is just an unfortunate side effect!
In general, bad bacteria are not natural residents of our gut, and enter upon ingestion of contaminated food. That is when the battle starts. Here are a few ways in which pathogens can establish their colony:
A few bad bacterial species can hide inside host cells, which are devoid of good bacteria. This strategy will avoid direct competition and combat with commensals, while providing a shelter and escape from immune system patrols.
Some pathogens can fight like knights by killing their commensal opponents using a sword-like shaped machinery (called the Type 6 Secretion System).
Other pathogens have evolved to use food sources not consumed by most commensal bacteria, giving them a growth advantage.
Finally, some pathogens secrete toxins, called virulence factors, to trigger a large immune response in which they are the only bacteria to survive. This last approach, similar to detonating a bomb, is a double-edged sword, as too much inflammation during an immune response is detrimental.
Ultimately, pathogens use devious tactics to invade our gut, proliferate and spread as much as possible. Although our immune system is well equipped to deliver violent blows to these enemies, sometimes we need backup in the form of modern medicine.
3) The ugly: How do good bacteria become opportunistic and cause disease?
Hidden among the crowd of commensal microbes are some unexpected enemies – the opportunistic bacteria. In normal conditions their numbers are kept under control by our immune system and they colonize the gut peacefully without causing harm. However, as soon as there is a breach in our military forces – the immune system and microbiota — they can cause disease. In most cases, opportunistic infections occur when our immune system is weakened. This can be due to an underlying infection such as acquired immunodeficiency syndrome (AIDS), or an immune dysfunction which may be genetic or chemically induced by chemotherapy or immunosuppressive drugs.
Helpless without its complete arsenal of immune cells, our body can no longer control the opportunistic bacteria, which will multiply to cause disease. Disruption of the normal commensal flora is also a cause of opportunistic infections. Our microbiome is susceptible to insults from typical pathogens (viruses, bacteria, fungi), which can disrupt its equilibrium and create favorable environments for opportunistic bacteria. An important example is the use of antibiotics, which typically kill all bacteria, good and bad. Wiping out all bacteria leaves an open territory to re-colonize after treatment, and some opportunistic pathogens can profit from the chaos and disorder that reign in the process of re-conquering the gut.
Summary & conclusion
From the outside the human gut appears mostly peaceful, protected by two loyal armies: the immune system and the microbiota. In reality, it is a battlefield where a permanent war wages between the good, the bad and the ugly bacteria to secure territory and resources for survival and multiplication.
With the discovery of the important role played by the microbiota, research on this topic is expanding, revealing that one individual’s microbiota is not the same as their neighbor’s, and that the composition of one's microbiota can change during their lifetime. In fact, many treatments favor a “natural” modification of the microbiota rather than synthetic drugs. This is the case for probiotic treatments, which aim to replenish the microbiome’s good bacteria. In extreme cases a complete transfer of healthy flora through faecal transplantation is necessary to restore a peaceful environment in the gut (For more information, you can watch this video).
If you want to know more about this fascinating world, here is a list of books and videos we highly recommend:
1. Cossart, P. and Hyber, F., 2021. Le monde invisible du vivant. Odile Jacob.
2. Sansonetti, P., 2020. Tu aimeras tes microbes comme toi même. Paris: Collège de France Editions.
3. Enders, G., Enders, J. and Liber, I., 2017. Le charme discret de l'intestin. Arles: Actes Sud.
4. Charming bowels. Giulia Ender (Book). https://www.goodreads.com/book/show/23013953-gut
5. Giulia Ender, TEDxDanubia. https://www.youtube.com/watch?v=NMsWFzSr04A
6. How we study the microbes living in your gut. Dan Knight, TED