The problem of antibiotic overuse has been a long-standing issue of the world. Not only does the overuse give rise to antibiotic resistance, scientists are also beginning to discover that antibiotics may potentially cause long-term behavioural changes.

Such findings will have a significant impact over how the healthcare community will utilise antibiotics if behavioural changes are indeed proven in humans. These vital medicines will have a different safety-over-benefit profile as their adverse effects no longer are limited to short duration.

Moreover, the Malaysian Ministry of Health has established that there is a high prevalence of patients who seek antibiotic treatment regardless of whether their conditions warrant the use of such medications or not.

Long-term behavioural changes in mice

Researchers from the McMaster University, Canada, investigated the effects of preterm exposure to antibiotics in mice. The team treated pregnant mice with penicillin V at a dose equivalent to the amount given to neonates (similar dose per weight basis), and continue the medication on the pups. These treated mice were then compared to another group which received additional probiotics (Lactobacillus) and tested when they reached adulthood.

The researchers detected changes in the mice behaviour even after they have reached adulthood, signifying a long-term impact on them. These mice exhibited “impaired anxiety-like and social behaviour, and display aggression”, wrote in the publication.

In addition, the team also observed significant and lasting effects on the gut microbiota, increased cytokine expression in the frontal cortex and altered blood-brain barrier integrity.

The comparison group that was given probiotics displayed a lesser degree of observed negative outcomes, including changes in gut bacteria and behaviour. This result thus suggested that there was a certain degree of beneficial effects from probiotics in protecting the mice.

The implications of the findings

Many will ask if the results can be translated meaningfully into the human population. At this point, the animal study results only indicated a possibility that humans will display similar reactions towards antibiotics.

However, senior author and molecular medicine specialist of the study, John Bienenstock, said “There are some early epidemiological-type studies suggesting that certain common psychiatric conditions are more prevalent if extensive antibiotic consumption occurred in early life.”

But caution should be exercised when interpreting the study results as well. Frequently, animal studies are not directly applicable to humans, as both species have a certain degree of physiological variations.

Although there are human studies that supported the association between antibiotics and psychiatric conditions, each study should be examined carefully in order to derive an accurate and precise conclusion.

Healthcare professionals play a vital role

In Malaysia, a study based on 2014 data showed that there was a significant disparity between the tendency to prescribe antibiotics in public versus private clinics. Private clinics had a much higher inclination to prescribe antibiotics and accounted for almost 87% of all antibiotics prescribed in the primary care setting.

As such, healthcare professionals have the obligation and duty to reduce the unnecessary use of antibiotics. There is now increasing evidence, in both animal and human studies, that support the necessity of moving away from prescribing antibiotics unless the condition absolutely warrants their use.

Pharmacists hence play a vital role in pioneering the stewardship of appropriate antibiotic usage that is consistent with the international and local guidelines. MIMS

Read more:
New research suggests possible link between antibiotics and colon polyps
Over-prescription of antibiotics due to misinterpretations between doctors and patients
Superbugs a growing concern in Southeast Asian hospitals

Leclercq S, Mian FM, Stanisz AM, Bindels LB, Cambier E, Ben-Amram H, Koren O, Forsythe P, Bienenstock J. Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior. Nat Commun. 2017 Apr 4;8:15062.
Ab Rahman N, Teng CL, Sivasampu S. Antibiotic prescribing in public and private practice: a cross-sectional study in primary care clinics in Malaysia. BMC Infect Dis. 2016 Dec 17;16(1):208.