Antibiotics, Probiotics, Superbugs and all that Jazz: For the Layman

Salmonella bacteria - a bacterium that occurs mainly in the gut, especially a serotype causing food poisoning
Salmonella bacteria – a bacterium that occurs mainly in the gut, especially a serotype causing food poisoning Credit:Pixabay

All this while, research, development, and production of drugs have primarily focused on “bad microbes”, that is, microbes that cause disease or illness to humans (and also livestock and plants). Hence, most efforts have been towards developing antibiotics against these microbes, particularly bacteria.

Since the discovery of penicillin in 1928 by Sir Alexander Fleming which helped save the lives of thousands of infected soldiers during the Second World War, antibiotics have proven to be a major boon to us. These days, antibiotics are available against most, otherwise life-threatening diseases including cholera, food poisoning and ulcers (e.g. those caused by E. coli, S. typhi, H. pylori andV. cholerae), meningitis (N. meninigitidis), wound infections (C. tetani and S. aureus), tuberculosis (M. tuberculosis), and pneumonia (S. pneumoniae). However, the increase in use of antibiotics and in particular their improper use (e.g. using antibiotics to treat viral infections, or not following the prescribed dosage and course for the treatment) over the last few years have given rise to “antibiotic-resistant” bacteria or what are referred to in news articles as “superbugs”.

Superbugs have risen as a result of (evolutionary) ‘selection pressure’ and have gained or developed genetic properties that make them resistant to commonly used antibiotics. An often-cited example is that of methicillin-resistant Staphylococcus aureus or MRSA, which is resistant to the antibiotic methicillin, and can cause pulmonary, skin, and urinary infections in humans and livestock. MRSA is especially fast-spreading in hospitals and nursing homes where patients with open wounds and weakened immunity are easily susceptible to infections. Therefore, developing strategies and potent drugs that can treat these superbugs has become a major field of research and clinical focus today.

However, it is not always about these ‘bad guys’. We know that pathogenic (or harmful) bacteria are only a handful compared to the number of “good” or non-pathogenic bacteria that are beneficial to us or at the least do not harm us. The most common examples are the bacteria in our intestinal gut that help us digest food, and the bacteria in the soil that decompose unwanted matter into manure for the plants. However, to derive the maximum benefit out of these good bacteria, maintaining the right balance between good and bad bacteria in the environment (e.g. gut and soil) is of prime importance.

Gut microbial flora in the intestine Credit: Pixabay
Gut microbial flora in the intestine Credit: Pixabay

What is a microbiome?

The collection or community of all microbes (usually includes bacteria, viruses and some other microbes too) that reside in an environment is called the microbiome. Based on the environment these microbes reside in, which can be a sample of the soil or the intestinal gut of humans, the microbiome can be accordingly termed; here, as the soil microbiome and the human gut microbiome.

You’ll be surprised that the human gut is home to an estimated 500 – 1,000 species of bacteria and also a few kinds of viruses especially bacteriophages (bacteriophages are equipped with the ability to invade and kill bacteria, but I’ll come to this in a while).

The gut microbiome interacts with our gut and has such an important role to play in our day-to-day well-being that many scientists consider the gut microbiome as an extra organ.

Why has the microbiome become so important all of a sudden now? Well, our grandmothers (and mothers too!) will not be surprised when we told them that our guts/stomachs determine our mood.

Age-old wisdom always suggested, “We are what we eat!”

However, it is only recently that the clinicians, nutritionists, psychologists, and the scientific research community have started to take notice of the microbiome as an important determinant of our physical and mental well-being, for keeping us immune to (common) diseases, and as a new approach to treat superbugs! Let me explain to you why and how this is so.

First, the why. Without going into too many details, like I mentioned before to a large extent it is the right balance between pathogenic and beneficial bacteria in our body’s microbiome that determines our well-being.

The population of beneficial bacteria helps to keep the population of pathogenic bacteria in check. However, if the pathogenic bacteria take over, which can happen, for example, through the consumption of contaminated food or water, we end up with a disease (e.g., cholera or gastroenteritis).

As mentioned before, most of the (common) diseases we pick up in this manner can be treated using antibiotics; however, the intake of antibiotics not only kills the pathogenic bacteria but also the beneficial bacteria. Therefore, it becomes necessary to replenish the population of beneficial bacteria in our bodies to continue to keep us healthy.

Why is the right balance of beneficial and pathogenic bacteria, important?

For the more scientifically inclined readers, who will not easily believe if I just told them that the right balance between beneficial and pathogenic bacteria is important, here’s a more concrete explanation and some recent and compelling scientific evidence supporting this point.

The microbial community in our body, in particular the gut microbiome, is not merely a collection of bacteria that help us in some tasks that we ourselves cannot do very well (e.g. digesting certain kinds of foods because we do not have the necessary enzymes to do so), but it is in fact a rich gene pool, of “exotic genes”. In fact the collection of genes that these 1,000-odd bacterial species carry is far more than the number of genes in any given human cell.

Importantly, these bacteria can exchange their genes among themselves just by coming in close proximity to one another. This is different from the (primarily vertical) evolutionary mechanism of gaining new genes through speciation. This kind of gene transfer is called horizontal or lateral gene transfer (LGT).

A bacterial species or strain can therefore evolve into, theoretically, an entirely new species simply by gaining/exchanging genes with another bacterial species via LGT. This means that an antibiotic-treatable bacterial strain can evolve into an antibiotic-resistant strain simply by gaining a gene that helps overcome the antibiotic (e.g. a gene that functions to pump out the antibiotic from the bacterial cell) by coming in close proximity of a virulent bacterial strain. And believe it or not, this can happen very fast, in a matter of a few minutes!

So, imagine what happens if there are a whole bunch of such pathogenic bacteria co-operating and exchanging virulence genes inside our gut? Sooner or later, all the bacterial population in the gut will turn virulent and antibiotic resistant. Therefore, it is important that we always maintain a large(r) population of beneficial strains to, if you may like to say, overpower the pathogenic strains, thus preventing these pathogenic strains from exchanging genetic material easily (pathogenic bacteria can still remain in the gut without causing any harm to the body as long as their population is low).

Diversity of the microbiome and its impact on our health

As important it is to maintain the right microbiome balance, so is to maintain a good diversity of the gene pool. This diversity determines the richness of the microbiome population; the more diverse the microbiome is, the more remarkable is its dynamics, its interaction with our gut, and therefore its impact on our health and physiology. A recent study by Zhernakova et al. (April 2016) published in the journal Science sought to study likely factors that go into determining the diversity of the human gut microbiome.

The authors sampled microbiota from 1,135 participants (primarily from a Dutch population) and found a total of 126 factors that determined microbiome diversity in this population. These factors included 31 intrinsic, 12 disease, and 19 drug factors. Among the most influential factors was consumption of buttermilk (yogurt churned with water / fermented milk with the cream removed): Two beneficial bacterial strains Leuconostoc mesenteroides and Lactococcus lactis found in buttermilk greatly enhanced the microbiome diversity of the human gut.

Probiotics are live bacteria and yeasts that are good for your health, especially your digestive system and these strains definitely fit the bill. They help keep the gut healthy and can be found naturally in the body or can be supplemented through certain foods like yoghurt, buttermilk etc.

On the other hand, consumption of alcoholic drinks, coffee, tea, high-fat (whole) milk, and sugary drinks had a negative impact on the microbiome diversity (note here that we are only talking of the impact on microbiome diversity and not arguing for or against the consumption of these substances). As expected, the use of antibiotics greatly reduced the microbial population.

Therefore, coming to the how, the answer is quite obvious: To maintain a healthy microbiome balance, consumption of food that enhances the microbiome diversity is how we do it, and this definitely includes buttermilk! (I will not go about suggesting dietary needs here, please consult a nutritionist/dietician for that, or see Recommended Reading below).

One other thing that remains to be explained is how do we overcome antibiotic resistance by maintaining a healthy microbiome balance? Well, partly, as explained before, if the population of beneficial bacteria can overpower the pathogenic bacteria, then this can to a great extent prevent the exchange of virulence genes, and thus prevent the gain of resistance among pathogenic bacteria.

Scientific research has of course been trying other avenues, and one such avenue is to engineer viruses called bacteriophages, which are potent natural killers of bacteria, to kill superbugs that cannot otherwise be treated using conventional antibiotics. This research is still in its early stages, but hopefully we should see some breakthrough in this direction over the coming few years. 

Recommended reading (for this weekend, if you like):

“I Contain Multitudes: The microbes within us and a grander view of life” by Ed Yong, HarperCollins Publishers, 2016.

“The mind-gut connection: How the hidden conversion within our bodies impacts our mood, our choices, and our overall health” by Emeran Mayer, Harper Wave publishers, 2015.

“The well-fed microbiome cookbook: Vital microbiome diet recipes to repair and renew the body and brain” by Kristina Campbell, 2016.