Just as an ocean nurtures marine life, human gut harbours trillions of microorganisms that form a complex ecosystem. The microbiome starts to develop before birth during foetal development and continues to diversify and establish its richness as one grows, thus playing a prominent role in shaping our unique existence.
The past decade has witnessed significant research in the field of the impact of the gut microbiome on health, and its role in many chronic and inflammatory diseases. Several studies emphasise the importance of restoring gut imbalances for better management of overall health and improving one’s quality of life. Alongside restoring gut health, researchers across the globe have also studied various environmental, physical, chemical and biological factors that could lead to gut imbalances and poor microbial diversities among individuals. One of these being antibiotics.
Antibiotics, which are common and often life-saving drugs, can also have the adverse effects of disturbing the gut microbiome and giving rise to antibiotic resistant bacteria. This has led to the problem of antimicrobial resistance, now a crucial field to be studied by the next generation of researchers.
The Journey of Antibiotics
In 1928, Alexander Fleming returned to his laboratory after time away. While looking through old experiments, he discovered that a particular mold was able to kill all the bacteria around it on an old petri plate. He went on to find that this secretion from the mold was capable of destroying multiple bacterial pathogens. He named the killing compound penicillin, after the mold itself- Pencillium notatum.
This breakthrough revolutionised medicine at the time, eventually saving countless patients from death by infection, and paved the path for the discovery of hundreds of antibiotics in the 21st century. But as time passed, and more antibiotics entered therapeutic circulation, the dark side of this practice emerged.
Overusage, improper administration, lack of disposal awareness, and self-prescription of antibiotics have few immediate effects, but introduce higher and higher levels of antibiotics into our bodies and surroundings. Besides this, antibiotics are now extensively used in agriculture and dairy sectors to ensure the health of animals and to prevent crop failures. Due to the persistence of these antibiotics in the environment, established through several routes, the bacteria too evolved- developing various methods of survival, known now as “resistance”.
Today many bacterial strains like E. coli, Staphylococcus aureus, Enterococcus have become resistant to common antibiotics resulting in recurrent infections in the blood stream, lungs, urinary tract (UTI), and causing diabetic ulcers and wounds in individuals, which are difficult to treat due to a lack of effective options and sometimes fatal.
Since the human gut affects nearly every metabolic process that occurs in the body, gut health is of utmost importance. The naturally occurring diversity of gut microbes is frequently disrupted by the inappropriate use of antibiotics, leading to the emergence of difficult-to-treat resistant and dangerous bacterial strains, as well as a disturbance in the ecology of the gut itself.
Antibiotic associated Gut Dysbiosis
Today, the silent pandemic of AMR (antimicrobial resistance) remains massively consequential on systemic and personal scales. Vulnerable populations like neonates, elderly, chronically ill, and immunocompromised individuals are under increasing risk of infection and comorbidities.
On an individual level, short-term antibiotic use can cause diarrhoea and infections, while long-term effects include allergies and obesity. Studies reveal that early life exposure to low-dose antibiotics can have significant long-term effects on gut health. Antibiotics can disrupt the intestinal ecosystem, promoting conditions favourable for growth of harmful bacteria. It has been shown that overuse of antibiotics could disrupt individual immune responses resulting in metabolic disorders.
Developments in genomics, metabolomics, and bioinformatics are rapidly changing the way the gut microbiome can be profiled, and how its interactions with other bodily systems can be understood and established. The influence of external factors on the gut microbiome is varied, therefore the reaction of this entity to antibiotics is expected to vary with the type of drug used, its concentration, and the route by which it enters the body.
Several studies have been undertaken to identify the changes caused by different ubiquitously used and prescribed antibiotics to the gut microbiome.
Azithromycin (a macrolide class of antibiotic) is known for its significant influence on the microbial diversity and richness of the gut microbiome. Macrolides, the structural class of antibiotics it belongs to, disrupt the microbiome longer, and cause a decrease in its diversity.
The analysis of Penicillin antibiotic class also revealed that exposure reduced the number of beneficial gut bacteria, including Lactobacillus and Bifidobacteria. These beneficial bacteria are part of the healthy gut flora, and help in fibre digestion, produce anti-inflammatory molecules, promote immune responses to fight off infections, and produce short chain fatty acids that help to maintain gut membrane integrity and prevent leaky gut.
Amoxicillin, a penicillin class antibiotic, negatively impacts the levels of Bacteroides fragilis and the beneficial Bifidobacteria in infants. A similar effect is seen in children exposed to Ampicillin (penicillin class) and Gentamycin (aminoglycoside class) where gut commensals Bifidobacteria and Lactobacillus are depleted, instead increasing others like Proteobacteria and Enterobacterisceae, and the genus Clostridium, of which several pathogens are part.
A few prevalent conditions that are linked to intestinal dysbiosis include:
Increased risk of infections- gut dysbiosis often leads to growth of pathogenic bacteria like Clostridium difficile that causes recurrent colon infections that might at times lead to life threatening conditions.
Metabolic disorders- Dysbiosis often leads to altered metabolism, increased fat storage, and tissue inflammation that results in obesity, diabetes and atherosclerosis.
Allergic conditions- Dysbiosis leads to poor immune system responses, predisposing individuals to allergic responses.
Inflammatory diseases- Dysbiosis often leads to leaky gut and intestinal inflammation leading to various inflammatory diseases like IBD and autoimmune diseases.
Neurological effects- Recent studies show that gut imbalances affect gut-brain axis bidirectional communications and functioning.
Impact on drug efficacy- Dysbiosis can alter the metabolism of drugs, affecting their efficacy and safety. For instance, antibiotics can change the gut microbiome, which may influence the response to other medications, including cancer therapies
Combatting antimicrobial resistance and related dysbiosis- you and the world
In the field of AMR, prevention is certainly better than cure. The biggest driver of prevention is adequate awareness, both for practitioners and the general public. Healthcare providers need to be cautious about prescribing antibiotics especially for non-serious infections to prevent unnecessary exposure. This includes evaluating the necessity of antibiotics and considering alternative treatments when appropriate to reduce the risk of metabolic disorders and developing resistance later in life. Parents must also be careful to adhere to prescribed courses, and must avoid self-prescribing antibiotics without clinical consultation.
Individual interventions for antibiotic-related dysbiosis:
Dietary interventions- Following a holistic lifestyle and including prebiotic and probiotic rich foods post antibiotic treatments could help in restoring the gut imbalances.
Fecal Microbiota Transplantation (FMT) – FMT along with probiotic supplementation is one of the most researched approaches to restore gut imbalances. As the name suggests, the healthy gut flora from a stool sample of a suitable donor is transferred to the individual who is in need of it. Though in its infancy, further research in this direction could pave the way for more efficient therapies for gut dysbiosis.
Systemic changes to reduce antibiotic prevalence:
Waste treatment- Since wastewater and sewage plants are hotbeds of bacteria, proper decontamination and antibiotic removal must be ensured to reduce bioaccumulation.
Hospital protocols- Hospitals are a common site of acquiring resistance due to shared equipment, care givers, and a large flux of vulnerable populations. Proper protocols must be put in place to avoid the transmission of resistant infections.
Public health policies- Public health campaigns can concentrate on informing the public about the possible dangers of excessive antibiotic usage. Campaigns could raise awareness of the importance of the gut microbiota to health and promote the judicious use of antibiotics.
Control use of Antibiotics in Animal Feed- Antibiotics reach humans not only through direct intake but also via bioaccumulation in food. Work must be done to reduce the dependence of the agriculture industry on feed antibiotics, such as improving access to vaccines, clean water, and adequate information.
Future Perspectives
Antibiotics, though indispensable in modern medicine today, have serious ramifications on an individual and collective, even worldwide level. While it is getting easier to understand the impact of individual antibiotics on the human body and the gut microbiome, the underlying takeaway is this- overuse of antibiotics can lead to gut dysbiosis and the development of resistance which leads to both ineffectiveness of a particular drug, and the development of hard to kill pathogens. Scaling this problem across various intersecting social, political, and economic layers, AMR worldwide must be controlled and reduced through robust regulations, international cooperation, and widespread awareness. Research for alternative methods of handling infections is a rapidly booming area, from the discovery of novel antibiotics, to combination therapy, immunomodulatory routes, drug repurposing and phage steering. This science must also translate from the bench to the field, requiring collaboration between academia, authority, and the industry.
