We have known for some time that one of the unwanted side effects of taking antibiotics is their disruption of friendly microbes in the gut. But now a new study that takes a closer look suggests the consequences of long-term antibiotic use could be even far-more reaching than we thought.
Writing in the journal Gut, Andrey Morgun, an assistant professor at the College of Pharmacy in Oregon State University, Corville, and colleagues hope the study will increase understanding of the widespread damage antibiotics cause to the gut and will offer new ways to investigate and offset the consequences.
Antibiotic use is widespread - around 40% of adults and 70% of children take at least one a year, and billions of animals are treated with them.
When used properly, antibiotics eliminate life-threatening infections, but around 1 in 10 people treated with them suffer adverse side effects.
Scientists are beginning to discover that antibiotic use - and overuse especially - is associated with a range of problems that affect, among other things, glucose metabolism, the immune system, food digestion and behavior. They also suspect it is linked to obesity and stress.
Prof. Morgun says:
"Just in the past decade a whole new universe has opened up about the far-reaching effects of antibiotic use, and now we're exploring it. The study of microbiota is just exploding. Nothing we find would surprise me at this point."
Antibiotics kill intestinal epithelium cells
For their study, the team used mice to look at the effects of four antibiotics commonly given to lab animals.
Previously, it was thought the antibiotics only killed gut bacteria and blocked some immune functions in the gut. But the new study shows they also destroy cells in the intestinal epithelium.
The intestinal epithelium is a velvet-like layer of specialized cells that lines the intestine and helps absorb water, glucose and essential nutrients into the bloodstream. It is also a barrier between the rest of the body and the huge colonies of bacteria that live in the gut.
The velvet-like appearance of the intestinal epithelium is due to the millions of tiny projections called villi that maximize the surface area of the epithelium.
The intestinal epithelium is home to an abundance of immune cells that live alongside the trillions of gut bacteria with whom they are in constant dialogue to maintain the delicate stability of the partnership between the host body and its bacterial colonies.
Antibiotics disrupt mitochondria and host-microbe signaling
The team also discovered that antibiotics affect a gene that is critical to the communication between host and gut bacteria. Prof. Morgun notes:
"When the host microbe communication system gets out of balance it can lead to a chain of seemingly unrelated problems."
Disruption in host-microbe dialog can not only disrupt digestion, cause diarrhea and ulcerative colitis, but new research is also linking it to immune function, obesity, food absorption, depression, sepsis, asthma and allergies.
The team also found that the antibiotics and bacteria that have developed resistance to them cause significant changes to mitochondria, leading to more cell death.
Mitochondria are tiny compartments inside cells that act like batteries - they convert food into energy for the cell. They also play an important role in cell signaling and growth and need to function properly for good health.
In evolutionary terms, mitochondria are descended from bacteria, which may explain why antibiotics attack cell components that most closely resemble them.
Studies like this support the idea that killing bad bacteria with antibiotics is perhaps not a good way to deal with infection - given the increasing list of side-effects and problems they cause. Prof. Morgun suggests boosting the healthy bacteria so they outcompete the unwanted ones might be a better approach.
The Medical Research Foundation of Oregon and the National Institutes of Health helped fund the study.
In January 2015, Medical News Today reported a study that suggested travelers taking antibiotics could be helping to spread antibiotic resistance. The researchers found travelers who take antibiotics for diarrhea are not only increasing their chances of contracting resistant intestinal bacteria, they could also be spreading them to their own countries.