I’m sure you’ve noticed that the gut microbiome is currently one of the hottest fields of research, emerging from relative obscurity to superstar status in the last 15 years. In fact, a staggering 12 900 articles focusing on the gut microbiota were published in medical and scientific journals between 2013 and 2017, 4000 of them in 2017 alone. Even more remarkable, this represents 80% of the total number of such publications over the last 40 years.
It’s old news that antibiotics have a devastating effect on the gut microbiome. A single 7-day course of broad spectrum antibiotics reduces gut microbial diversity (a crucial measure of the health of the gut ecosystem) by approximately 25%, with the core microbiota dropping precipitously from 29 to 12 taxa (bacterial ‘families’).
In addition, there is a steep increase in the numbers of a family of bacteria called Bacteroides after antibiotic use. Bacteroides species normally exist peacefully in the human gut, carrying out a number of useful tasks, but an overgrowth of them is associated with insulin resistance, increased body fatness and inflammation.
Normally, the numbers of Bacteroides in the gut microbial community are kept in check by other bacteria which compete with them for food, and also produce substances such as which inhibit their growth. Unfortunately, Bacteroides are able to develop antibiotic resistant more readily than most of the other gut microbes. When antibiotics wipe out their competitors, Bacteroides seize the day, and stage a takeover of our gut. Once dominant, they further reduce microbial diversity and push us toward an inflammatory, insulin-resistant state.
And the devastation wrought by antibiotics can persist long after the final pill is taken. 6 months after taking ciprofloxacin, an antibiotic that is considered to have relatively minor effects on the gut microbiome, certain bacterial species that were found in patients’ guts before antibiotic treatment, but disappeared after it, had still not returned. The consequences of extinction of species of bacteria that normally inhabit the gut are simply not known, but it is well established that any reduction in microbial diversity is associated with weight gain and poorer health outcomes.
A study of the long-term effects of the antibiotic clindamycin found that the gut microbiota did not bounce back to their original composition even 2 years after a 7-day course of treatment.
The effects of antibiotic use on the gut microbiota of babies and children is even more dramatic and persistent. Microbial diversity is low at birth, gradually increasing until around 3 years of age, when a child’s microbiome comes to resemble that of an adult. But early-life use of antibiotics can prevent that all-important diversity from developing in the first place. Antibiotic exposure during infancy is associated with a higher risk of childhood obesity, and type 2 diabetes in later life.
Furthermore, antibiotic treatment increases the prevalence of antibiotic resistance genes in the bacteria that inhabit our gut. For example, a drug ‘cocktail’ commonly used to eradicate Helicobacter pylori, a bacterium associated with stomach ulcers and increased risk of stomach cancer (clarithromycin, metronidazole, and omeprazole) was found to cause high-level clarithromycin resistance in enterococci, a common family of gut bacteria. This resistance persisted for 1 to 3 years after treatment. In other words, drugs used to wipe out one species of bacteria caused other species to become antibiotic resistant.
Unfortunately, antibiotics are very far from being the only drugs that adversely affect our gut microbiome. A study published in March 2018 tested the effects of over 1000 drugs currently on the market on 40 strains of bacteria typically found in the human gut. A whopping 24% of these drugs – across all therapeutic classes – were found to inhibit the growth of at least one bacterial strain.
The worst offenders when it came to messing with the microbiome were antipsychotics, which are increasingly prescribed to children and adults who do not have psychotic illness, but have not responded to typical antidepressants. The researchers also found non-antibiotic drugs could promote antibiotic resistance.
A systematic review published in February 2018 summarised what is known about the effect of 6 classes of drugs – proton pump inhibitors (PPIs), metformin, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, statins and antipsychotics – on the gut microbiome.
They found that PPIs, metformin, NSAIDs, opioids and antipsychotics were all either associated with increases in numbers of Gammaproteobacteria (including Enterobacter, Escherichia, Klebsiella and Citrobacter), or Enterococcaceae, which are often pathogens isolated from bloodstream infections in critically ill patients.
PPI users had clear signs of dysbiosis – imbalanced gut flora – including decreased Clotridiales and increased Actinomycetales, Micrococcaceae and Streptococcaceae. This imbalance is associated with increased susceptibility to Clostridium difficile infection, a serious, even life-threatening gastrointestinal infection. In fact, after just 4 weeks on a PPI, patients were already manifesting microbiome changes that are associated with a predisposition to C. difficile infection. (See my article The purple pill that kills for the low-down on PPIs, which are currently massively overprescribed.)
Antipsychotic treatment resulted in a decreased ratio of Bacteroidetes:Firmicutes in the gut microbiome, mirroring trends previously seen in obese patients. This class of drugs is known to increase the risk of weight gain and metabolic syndrome.
Diabetics taking metformin had significant decreases in the number of Intestinibacter, Coprococcus comes, Clostridium bartlettii, Eubacterium siraeum and Peptostreptococcaceae, microbial species which produce butyrate – a substance which improves insulin sensitivity. Since type 2 diabetes is essentially a condition of impaired insulin sensitivity, this is deeply concerning.
On the other hand, metformin use was associated with a significant increase in Escherichia, Shigella, Klebsiella, Citrobacter and Salmonella enterica, bacterial species that, like Bacteroides, can have adverse effects when they overgrow.
The authors of the review pointed out that reduced microbiome diversity
“has well-documented associations with inflammatory states and diseases… [including] allergy, inflammatory bowel diseases, type 1 diabetes mellitus and multiple sclerosis, as well as colorectal cancer and metabolic disorders like obesity and T2D mellitus which primarily affect Western countries.”
These recently published studies should give serious pause for thought. We know so little about our gut microbiome, despite the flurry of recent publications. The fact that commonly prescribed drugs cause extensive changes to the balance of bacteria that inhabit our guts is deeply concerning. Drugs can be life saving, but all often they are prescribed when poorly indicated (or not indicated at all), and without anything remotely resembling an informed consent process, in which the doctor explains to the patient the risks and benefits of treatment, and the alternatives to drug treatment.
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