By Dr. Priyom Bose, Ph.D.Reviewed by Lily Ramsey, LLMDec 19 2024

Antibiotics play a major role in bacterial infection treatment; however, their overuse disrupts commensal microbiota. Although probiotics can effectively alleviate antibiotic-associated diarrhea, they do not restore the gut microbiota to its pre-antibiotic state. In the future, more studies are required to understand whether any specific probiotic preparation could effectively restore gut microbiome diversity and composition after antibiotic use.

Study: Antibiotic-perturbed microbiota and the role of probiotics. Image Credit: New Africa/Shutterstock.com

Recently, scientists explored the available literature to evaluate the efficacy of probiotics in preventing gut microbial disruption and their capacity to restore it after antibiotic treatment. This review is available in Nature Reviews Gastroenterology & Hepatology.

The benefits of antibiotics and their effect on human gut microbiota

According to the Global Research on Antimicrobial Resistance Project, there has been an approximately 46% increase in antibiotic consumption in the last two decades.

However, the antibiotic consumption rate varies significantly across regions and income levels. This observation highlights the need for targeted strategies to manage antimicrobial resistance (AMR).

The primary benefit of antibiotic use is managing severe acute bacterial infections. Besides the benefits, some individuals develop severe allergic reactions (e.g., anaphylaxis) to certain antibiotics, including penicillin.

Antibiotics also increase the risk of gastrointestinal infections in some people, possibly due to pathogenic expansion owing to compromised colonization resistance.

Antibiotics also cause gut microbial dysbiosis. Different antibiotics affect the gut microbiota in various complex ways; for example, lincosamides decrease Gram-positive bacteria, surge resistance genes, and reduce Bacteroidota diversity.

Antibiotic misuse is associated with its availability without prescription in some regions. AMR also occurs due to the inclusion of antibiotics in animal feed for rapid weight gain. This practice might not only affect animal's health but also lead to the emergence of drug-resistant bacteria that could infect humans.

Probiotics and antibiotics

Probiotics are live microorganisms that help maintain or improve the gut microbiome. Scientists across the world have focussed on uncovering how probiotic use, along with antibiotics, affects the gut microbiota.

They explored the potential of probiotics in preventing or restoring antibiotic-associated microbiota disruption and antibiotic-associated clinical outcomes.

An extreme heterogeneity regarding dosage, efficacy, and probiotics formulations has been observed. This heterogeneity has been attributed to treatments prior to starting antibiotic and probiotic administration, the patient's age, the antibiotic regimen, or pre-existing diseases. Multiple research findings indicate that probiotics can moderately reduce the duration of diarrhea by approximately one day.

The lack of baseline data on a 'healthy' reference microbiota limits scientists from being able to conclude whether probiotics mitigate antibiotic-induced perturbation of the microbiota.

A very limited number of studies have used high-throughput microbiota readout methods (e.g., metagenomics and 16S rRNA gene sequencing) to assess the effects of probiotics on the antibiotic-exposed microbiota.

These studies have indicated the beneficial effects of probiotics on restoring the gut microbial dysbiosis caused by antibiotics. For instance, probiotic-treated adults exhibited a significantly higher α-diversity in their gut than the placebo-treated control group.

Interestingly, probiotic treatment with only Saccharomyces boulardii did not exhibit any changes in the antibiotic-induced changes in α-diversity and β-diversity; however, a selective shift in the relative abundance of several taxa was observed.

S. boulardii co-administration with Parabacteroides, Escherichia, and Enterobacter species increased Odoribacter and Stenotrophomonas and reduced Ralstonia modestly.

A pediatric random clinical trial (RCT) has shown that the effects of probiotics are dependent on the antibiotic type used. Probiotics used alongside penicillin resulted in the restoration of four of the affected operational taxonomic units.

Studies have also revealed that certain probiotic formulations disrupt certain bacterial taxa compared to the placebo group.

Commensal gut bacteria act as a reservoir for antibiotic resistance genes (ARGs), and antibiotics employ a selective pressure that induces the expansion of drug-class-specific ARGs in this reservoir, which is collectively termed the gut resistome. This could result in the horizontal transfer of ARGs to pathogens.

Theoretically, probiotic bacteria could counteract resistome expansion through the omission of resistant strains or by creating an intestinal environment that disfavors horizontal gene transfer. Several studies have shown that probiotics could reduce ARG burden in adult patients.

Future research outlook

From now on, it will be important to have a theoretical definition of what constitutes microbiota recovery and what would be a desirable outcome. In the past, the effect of probiotics on the microbiota was predominantly done using culturing or qPCR amplification.

However, these approaches provide a partial (and sometimes biased) assessment of the microbiota. Sequencing-based approaches can help reduce the bias but are prone to other challenges.

The beneficial effects of probiotics on the microbiome can be quantified by measuring virulence factors. The effects of probiotics on the antibiotic-perturbed microbiome can be better understood by incorporating multiple analytical approaches and combining experimental techniques.

It could be worthwhile complementing microbiome profiling with more direct measures quantifying host health status.

Concerning research gaps, more work is needed to study whether differences in microbiota stability in otherwise healthy individuals are associated with specific readouts of health or either short-term or long-term health in the host.

The baseline stability of the microbiota needs to be established also. Existing research has not pushed the causality frontier between microbiota states and health, and this needs to be addressed going forward.

Other areas of potential research include the long-term effects of gut microbiota modulation, precise definitions for microbiota restoration, antibiotic perturbation, and probiotic-induced recovery, and whether it makes sense to focus on microbiome features such as metabolic functionality and the resistome.

Journal reference:

Szajewska, H. et al. (2024) Antibiotic-perturbed microbiota and the role of probiotics. Nature Reviews Gastroenterology & Hepatology. 1-18. doi: https://doi.org/10.1038/s41575-024-01023-x.