by Mae Chan
While the adverse effects of antibiotic use on the
human microbiome are well
documented, other commonly used medicines are having a similar
impact, warn researchers.
We have a symbiotic relationship with friendly bacteria that covers
a lot of territory. That colony of helpful bacteria is sometimes
called our "forgotten organ."
gut flora imbalance allows
pathogenic bacteria and fungi to infect our bodies.
Our bodies rely on proper
enzymes and healthy microbes to work with pathogenic bacteria and to
produce anti-bacterial cultures in order to strengthen the
intestinal walls and to support our immune system.
If the bacteria in our digestive systems are out of balance (or
absent), a chain of undesirable events is initiated including
improper digestion, malnutrition and incomplete absorption of
The beneficial bacteria
in our digestive tracts produce necessary vitamins including B
vitamins and K vitamins.
Without the beneficial
bacteria in our digestive tract, vitamin deficiency can result.
A host of drugs designed to target human cells, and not microbes,
may be associated with microbiome composition changes, warn
researchers from the the European Molecular Biology Laboratory
These include anti-diabetics, proton pump inhibitors, non-steroidal
anti-inflammatory drugs and atypical antipsychotics, they say.
Writing in Nature (Extensive
Impact of Non-Antibiotic Drugs on Human Gut Bacteria),
the team behind the study describe the full extent of the effects,
which suggest that over a quarter (250 out of 923) non-antibiotic
medications reduced the growth of at least one species of human gut
bacteria in vitro.
Predictably, 78% of the antibacterial drugs examined were active in
inhibiting numbers of one or more species.
However, the proportion
(27%) of non-antibiotic 'human targeted drugs' (HTDs) that were also
found to be active was not anticipated, according to the scientists.
"The number of
unrelated drugs that hit gut microbes as collateral damage was
surprising," said study senior author Professor Peer Bork.
"Especially since we
show that the actual number is likely to be even higher."
There are two reasons for this potential underestimate, suggested
Firstly, concentrations of the drugs in the ileum and colon may be
different to plasma levels, which is where they are typically
drugs would inhibit bacterial growth if probed at higher doses,
closer to physiological concentrations," noted Bork.
researchers only screened a representative sample of a healthy
microbiome containing 38 species (mostly beneficial 'commensal'
varieties, but also including four pathogenic species).
In practice, the human
gut contains hundreds of species and an even larger strain
diversity, the researchers explained.
that if more gut species were tested, the fraction of
human-targeted drugs with anti-commensal activity would
increase," Bork added.
Most drugs analyzed in
the study were active against small subsets of bacteria.
However, 40 medications
reduced the abundance of 10 or more strains.
Effects To Antibiotics
The researchers found not only that side effects from HTDs resembled
of antibiotics, but also that
resistance mechanisms of microbes to the two types of drugs had a
large degree of overlap.
"This shift in the
composition of our gut bacteria contributes to drug
side-effects, but might also be part of the drugs' beneficial
action," explained Bork.
The latter finding
highlights the previously unnoticed risk that non-antibiotic
medicines may also promote antibiotic resistance.
"This is scary," said
Dr. Nassos Typas, "considering that we take many non-antibiotic
drugs in our life, often for long periods. Still, not all drugs
will impact gut bacteria and not all resistance will be common.
In some cases,
resistance to specific non-antibiotics will trigger sensitivity
to specific antibiotics, opening paths for designing optimal
The results of this study will be useful in further research
exploring drug-microbe interactions and could pave the way for the
development of personalized solutions, suggested Dr. Georg Zeller.
"We are excited to
move on and explore drug-microbe interactions in complex gut
microbial communities, as this will help us understand how
individuals sometimes respond differently to the same
medication," said Zeller.
Professor Kiran Patil
"This is just the
beginning. We don't know yet how most of these drugs target
microbes, how these effects manifest in the human host, and what
the clinical outcomes are.
We need to carefully
study these relationships, as this knowledge could dramatically
improve our understanding and the efficacy of existing drugs."