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  • Writer's pictureDoctor Anastasia

Microbiotoxicity: a plea from your patient's microbiome

We've all been there. It's 16:50 on a Friday, and the 63-year-old lady in Bay 3 just spiked a fever. She isn’t septic, and there’s no obvious focus of infection. But you start some antibiotics, just in case. After all, the on-call team can review with the bloods and chest x-ray, and no one wants to be the doctor responsible if she's fallen into a septic heap by then. It's just a couple of doses - what's the harm, right?

Let's talk about microbiotoxicity: the unintended bystander effect of antibiotics on your patient's microbiome. I recently came up with this term, and now that it's been published in our latest paper, I think it's time we started using it. We already consider the nephrotoxic, hepatotoxic and cytotoxic effects of the drugs we prescribe... So how can we weigh the intended benefits of antibiotics against their potential harms for each individual patient?

To do this, I propose three adjustments in our collective mindsets:

1) The microbiome is the largest (and most over-looked) human organ system

  • The microbiome is the total community of microbes living on and in a host, along with their metabolites, genetic material and local environment. At least 50% of the cells in our bodies are bacterial, and over 99% of our genes. There's no escaping it: each one of us is a human-microbial super-organism, or a so-called "holobiont".

  • The majority of our 30 trillion resident bacteria are not only harmless to us, but actually integral to human health. Our gut microbes produce essential vitamins, neurotransmitters, hormones and short chain fatty acids (SCFAs) like butyrate (which suppress oncogenesis, inflammation and appetite). The microbiome also regulates metabolism, adaptive immunity, and mucosal barrier integrity.

  • Harm the microbiome, harm the human: Once you start thinking of the microbiome as an organ system, and yourself as a human-microbial super-organism, it's not surprising that damaging this organ system can harm human health. There is growing evidence that the deluge of non-communicable diseases like diabetes, asthma, obesity and even cancer are related to microbiome disruption. Mouse models suggest that this association may be causal, and is driven by the systemic inflammatory effects of microbiome disruption ("dysbiosis").

  • Such disruption often occurs in early life, with caesarean-delivered and formula-fed infants demonstrating altered microbiome profiles and more adverse health outcomes than vaginally-delivered and breastfed infants. But the microbiome can be harmed throughout life, and the two biggest culprits are diet and (you guessed it) antibiotics...

Infographic of microbiome functions and products

2) Antibiotics are inherently microbiotoxic

WHY do antibiotics harm the microbiome?

  • Immediately after taking a course of antibiotics, there is a marked drop in the total number of bacteria and bacterial species, especially health-associated keystone bacteria like Bifidobacterium, Lactobacillus and Bacteroides species.

  • There is also a bloom of potential pathogens like Enterobacterales, Enterococcus, Clostridium and Candida, which can cause healthcare-associated infections (like C. difficile diarrhoea and yeast infections).

  • The total burden of antimicrobial-resistance (AMR) genes ("resistome") increases, which may lead to AMR infections, and transmission of these genes to others.

  • It can take weeks or even over a year for these changes to resolve.

WHO is most affected?

  • These microbiotoxic effects may be greater in early life - babies receiving antibiotics are 37% more likely to develop asthma than untreated babies, and 82% more likely if antibiotics are given in the first week of life. Persistent microbiome differences are even seen in babies whose mothers received antibiotics before delivery.

  • This is a big deal - 80% of children currently receive antibiotics by age 2, and about 25% of all pregnant women receive antibiotics!

  • Other groups at higher risk of microbiotoxicity are elderly, immunosuppressed, or co-morbid patients (especially those with intercurrent pro-inflammatory conditions).

WHICH antibitoics are most microbiotoxic?

  • Not all antibiotic courses are equally microbiotoxic! Broad (versus narrow) spectrum, long (versus short) courses, gram-negative and anaerobic (versus gram-positive) cover, combination (versus single agent), and repeated (versus single) courses are MOST microbiotoxic.

  • That being said, even a single antibiotic dose has been found to cause significant change in the microbiome.

Infographic of microbiotoxicity risk factors and effects

3) Microbiotoxicity should be considered for every antibiotic prescription

  • If the microbiome is a complex and indispensable organ system, then our duty of care extends accordingly to our patients' microbiomes.

  • In cases of severe infection, these unfortunate microbiotoxic effects may be entirely justified and unavoidable, and we absolutely do not suggest withholding antibiotics when clinically indicated. Rather, each prescription should involve careful weighing of the risk of infection against the risk of antibiotic-induced microbiotoxicity.

  • Almost none of our current antibiotic guidelines consider the effect on the microbiome. So, while we don't suggest ignoring these guidelines, we acknowledge that they are necessarily incomplete until microbiome harms are addressed.

  • As clinicians and the public become increasingly aware of the importance of the microbiome, talking about microbiotoxicity may offer a useful framework for negotiating antibiotic decision-making with patients, and even for challenging inappropriate prescribing by fellow clinicians.

  • Traditional antimicrobial stewardship often focusses on the "big picture" view of antimicrobial resistance. But it can be difficult to consider this apocalyptic and pervasive problem when faced with the patient in front of you. Microbiotoxicity reframes this, by focusing on weighing the risks and benefits of each prescription.

  • In future, there may be a role for mitigation strategies, like probiotics, when prescribing antibiotics, but these are not yet recommended by guidelines.

  • There are also therapies for treating microbiome disruption, such as faecal microbiome transplant, and novel microbiome-based drugs like Rebyota and Vowst.

Infographic weighing antibiotic indication against microbiotoxicity

So, here's a plea from your patient's microbiome, and from me: I urgently invite you to add the term “microbiotoxicity” to your clinical vocabulary as a call to arms... A reminder to first do no harm, microbes and all.

Please check out the full paper (open access in Current Opinion in Infectious Diseases) and share with your colleagues, and sign up to Hello Micro to receive emails about new blog posts and video tutorials :-)


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