The Gut Microbiome and Antimicrobial Resistance
We must consider the impact of misusing antibiotics on our gut microbiomes, overall health, and economy.
Introduction
The gut microbiome, containing between 10 and 100 trillion microbial cells, and composed of over 25000 bacterial species, plays a key role in the immune system and digestion, as well as some more obscure functions. Microbiota are the collection of microorganisms which have colonised a location, including bacteria, fungi, viruses and archaea (although, in this article, I will mainly refer to bacteria for simplicity). The incredible diversity of the gut is is hard to exaggerate - humans share over 99% of our DNA, but less than 10% of microbial species. In recent years, it has become easier to study the microbiome, due to advances in technology, and the fact that it is now cheaper to carry out genetic sequencing.
Role of the Gut Microbiome
The gut consists of the entire gastrointestinal tract, from the mouth, along the entire digestive pathway. There is a wide range of bacterial species:
In different parts of the GI tract, the environments are adapted to different functions, leading to different conditions, and therefore different bacterial species.
For example, in the colon, the epithelium (a thin layer of tissue on the colon wall) regenerates very frequently (every 3 - 5 days), as a protective mechanism against infection or injury, which means that the cells must respire (to generate energy for protein synthesis) at a high rate, using up oxygen very quickly. This means that the environment of the colon is kept in hypoxia (low levels of oxygen). As a result, the bacteria which reside in the colon are mostly anaerobic (respire without using oxygen).
Lifestyle factors give rise to different microbial compositions, including the method of birth, diet, and surrounding environment.
For example, the bacteria in the colon are adapted to break down fibre, releasing short chain fatty acids, which make the pH of the colon lower (more acidic). Acidic conditions favour certain bacterial species, and also prevent some harmful bacteria from growing. Therefore, foods that are high in fibre, such as fruit and vegetables, impact the type of bacteria in the colon.
The main divisions of bacteria in the gut microbiome are Firmicutes and Bacteroides, with less of Actinobacteria, Proteobacteria and Verrucomicrobia. Different bacteria perform different functions. Symbiotic bacteria are beneficial for the host organism, whereas pathogenic bacteria are harmful. In a healthy microbiome, most of the bacteria are symbiotic:
For example, one of the functions performed by Firmicutes and Bacteroides is the fermentation of carbohydrates in the colon, producing short chain fatty acids, which provide energy.
Bacteroides and Actinobacteria also induce the release of sIgA, an antibody which coats the microbiota, so that they are more resistant to being digested by pathogens.
Antimicrobial Resistance
Antimicrobial resistance, according to the World Health Organisation, is 'when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines, making infections harder to treat and increasing the risk of disease spread, severe illness and death’. The main cause is misusing antibiotics - either through overuse, or uncompleted treatments.
When MDR (multi-drug resistant) bacteria enter the body, the person must rely on their immune system to fight it, the gut microbiome being a key part of this. However, antibiotics can also affect the microbiome, causing dysbiosis; a disruption to the stability of the normal gut microbiome, which reduces the ability of the microbiome to protect against colonisation. Usually, the microbiome prevents colonisation by pathogenic microorganisms, by:
Activating the immune system
Producing acidic substances (making it impossible for the pathogens to survive)
Competing with pathogens for nutrients and oxygen
If this ability gets disrupted by dysbiosis, MDR harmful bacteria are more likely to spread, especially as genes for antibiotic-resistance are transmitted particularly rapidly among bacterial species.
The World Health Organisation has declared antimicrobial resistance to be among the 10 top global public health threats facing humanity. It has been estimated that by 2050, deaths directly caused by this problem will equal that of cancer in 2020, at 10 million people annually. There are two main consequences to consider:
Inequity - the UNEP has stated that this crisis is ‘disproportionately affecting countries in the Global South’, and insufficient sanitation increases the spread of MDR bacteria.
Economic impacts - it is expected that GDP will fall annually by at least $3.4 trillion by 2030, resulting in around 24 million more people in extreme poverty.
Implications
Clearly, the relationship between the symbiotic species in our gut microbiomes, and our use of antibiotics must be addressed, for both global health, and economic reasons. We must examine exactly how and when we use antibiotics so that we do not sabotage future generations, by fostering MDR bacteria.
We can also consider the applications of our knowledge of the gut microbiome to promote health and combat infectious disease, stressing the consumption of foods beneficial for the gut, to reduce infection rates in countries which are less capable at providing medical aid. Prebiotics are also an important route to consider. They are currently unregulated by the FDA, so often pills do not contain the ingredients listed, however, with more controlled regulation, they could be very effective in offsetting the negative effects of antibiotics.
Bibliography:
https://www.hsph.harvard.edu/nutritionsource/microbiome/
https://www.medicalnewstoday.com/articles/307998
https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance