Can antibiotics promote the growth of harmful bacteria in the gut?
Antibiotics are lifesavers, but they can also have unexpected consequences. A new research shows how antibiotics can promote the growth of harmful bacteria in the gut and points the way to new treatments.
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Antibiotic resistance is a pressing global public health concern that resulted in 1.27 million deaths worldwide in 2019 1. One approach to prevent these infections, particularly Carbapenem-resistant Enterobacteriaceae (CRE), is to understand what drives the colonization of the intestine by these bacteria.
Your gut is home to a diverse community of beneficial bacteria that help prevent harmful pathogens like CRE from taking hold. Healthy gut bacteria have mechanisms to prevent the colonization of pathogens, such as production of beneficial molecules, also called metabolites, like (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) ). Broad-spectrum antibiotics disrupt these mechanisms and promote the growth of antibiotic-resistant bacteria.
40%–50% CRE infections are associated with mortality rates as high as 40%–50%
Antimicrobial resistance: a global threat, an international response
The yin-yang effect!
Are Broad-spectrum antibiotics responsible for increased risk of infection with CRE? Yes, according to the 2023 study published in Nature Communication by a researcher from Imperial College London 2.
Eight broad-spectrum antibiotics were tested on faecal samples from healthy human donors:
- meropenem
- imipenem/cilastatin
- ertapenem
- piperacillin/tazobactam
- ciprofloxacin
- ceftriaxone
- ceftazidime
- and cefotaxime
These antibiotics are known to promote susceptibility to CRE intestinal colonisation. The researchers used a specific growth medium to measure: 1) the impact of the antibiotics on the abundance of gut commensal taxa from the faecal microbiota, 2) nutrients and microbial metabolites concentration in the faecal cultures.
The study showed that broad-spectrum antibiotics, often used to treat infections, can disrupt the balance of your gut microbiota. They reduce the population of beneficial bacteria (including Bifidobacteriaceae and Bacteroidales), making it easier for CRE to flourish.
What was even more interesting is that when piperacillin/tazobactam were tested in a mouse model, these antibiotics not only affected the bacteria but also altered the environment in gut. They increased the availability of certain nutrients, like amino acids, that support the growth of CRE. This nutrient-rich environment becomes a breeding ground for the resistant bacteria.
On the flip side, these antibiotics decreased the concentration of microbial metabolites, such as butyrate or propionate, some of which inhibit the growth of CRE. When these metabolites are depleted, CRE has fewer obstacles in its path.
Short-chain fatty acids (SCFAs) are key metabolites produced by beneficial gut bacteria that act as guardians of gut health. However, the indiscriminate use of broad-spectrum antibiotics can disrupt the gut microbiota, leading to a decrease in SCFA production and an increase in the growth of antibiotic-resistant bacteria.
As medical professionals, we must be aware of the intricate interactions within the gut microbiota. By carefully considering the impact of antibiotics on the delicate balance of the microbiota, we can take a step closer to combatting antibiotic resistance effectively and preserving the health of our patients.
What is the World AMR Awareness Week?
Each year since 2015, the WHO organizes the World AMR Awareness Week (WAAW), which aims to increase awareness of global antimicrobial resistance.
Held on 18-24 November, this campaign encourages the general public, healthcare professionals and decision-makers to use antimicrobials carefully to prevent the further emergence of antimicrobial resistance.
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