In a recent review and meta-analysis published in BMC Medicine Journal, the researchers evaluated previous work by conducting controlled trials of patients receiving antibiotic therapy with and without antibiotic supplementation.
Their results clarified that probiotic supplementation did not change gut microbiome diversity between the case and control cohorts, contradicting popular belief.
Study: Probiotic supplementation during antibiotic treatment is unwarranted in maintaining gut microbiome diversity: a systematic review and meta-analysis. Image credit: PHOTOGRIN/Shutterstock.com
Effects of antibiotics on the intestinal flora
It is known that antibiotics qualitatively alter the intestinal microbiota, significantly decreasing the density of some species and, in extreme cases, leading them to extinction.
This results in a low diversity gut microbiome and allows for the inclusion of potentially pathogenic bacteria Staphylococcus aureus, Clostridioides difficileAND Clostridium perfringens, to dominate intestinal bacterial communities. This imbalance, called “dysbiosis,” has been associated with numerous health conditions such as neurological dysfunction, inflammatory bowel syndrome, and cancer.
The gut microbiota usually recovers to normal without medical intervention. However, the duration of recovery can vary greatly based on the dose, spectrum, and duration of antibiotic treatment, patient age, and most importantly, the time between successive courses of antibiotics.
Previous research had estimated two weeks for this recovery in healthy young adults, but this increases dramatically if a new course of antibiotics is given before normal is achieved.
Probiotics, preparations containing live bacteria, yeast, or combinations of these microbes, are often prescribed to prevent or reverse dysbiosis. Research has investigated the clinical outcomes of taking probiotics during treatment, with several reports of their effectiveness in restoring the post-treatment microbiota. However, their impact on faecal microbiota diversity remains lacking.
Significant interindividual differences in gut flora species have historically confused definitions of “normal gut microbiota composition,” making it difficult to establish standardized measurement methods.
Researchers and clinicians borrow measures of ecological diversity, particularly diversity indices α and β, to signal the abundance and diversity of the gut community. α diversity is the diversity within a sample, while β diversity is the diversity between different sets of samples.
About the study
In the present study, researchers used meta-analytic approaches to evaluate the effects of probiotic supplements in maintaining or restoring gut microbiota diversity during antibiotic treatment.
They began by collecting 19,596 records from the Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases. They then used the PICO-S format (population, intervention, comparison, outcome, and study design) to screen the studies.
Screening of the title, abstract and full text identified 15 publications for the qualitative synthesis (review) and five for the quantitative one (meta-analysis). The review included 887 patients, while the meta-analyses reported 335 patients. The researchers extracted study characteristics, cohort details, descriptions of antibiotics and probiotics, and the results of each study.
The Shannon diversity indices and observed operational taxonomic units (OTUs) were subsequently calculated for the quantitative analyses.
Finally, assessments of bias and certainty were conducted using the Cochrane risk-of-bias (RoB2) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools, respectively.
Study results
The present review and meta-analysis did not reveal that probiotic consumption can prevent antibiotic-induced dysbiosis.
The Shannon diversity of the gut microbiome between cases (patients consuming probiotics) and controls (those not consuming probiotics) was, on average, only 0.23 (not significant), with only one of the five included studies showing a statistical difference between the cohorts. The OTU results were similar, with no observable differences between the cases and control cohorts.
Three of nine studies reporting α-diversity indices showed improvements in α-diversity indices between case and probiotic supplementation groups. However, these signals were weak and remained unexplained.
Only one of five studies reporting β-diversity showed improvements for case cohorts. However, these were not significant enough to merit the positive reputation probiotics currently enjoy.
Taxonomic analyzes of the gut microbiome have revealed that at the phylum level, firmicutes AND Bacteroidetes representation has decreased significantly and have been replaced by Proteobacteria after administration of antibiotics.
These results were consistent regardless of the cohort tested. These alterations were spontaneously rectified in up to 56 days, with probiotics not contributing to the acceleration of normality.
At the gender level, probiotic supplementation has been shown to maintain the level of Bifidobacterium gender, which in the control group decreased during antibiotic treatment. It took up to 35 days for people not consuming probiotics to recover to pre-treatment levels.
Conclusions
In the present study, the researchers used a systematic approach and a separate meta-analysis to evaluate the benefits of probiotic consumption on gut microbiota maintenance during antibiotic treatment.
Their findings debunk the notion that consuming probiotics during treatment can prevent or reverse changes in gut flora, a characteristic result of antibiotic administration.
No changes in gut microbiota were observed between patients who consumed probiotics and those who did not in the observed operational taxonomic units meta-analysis. The Shannon Diversity Indices reported similar results, with only one study reporting slight improvements in diversity measures on probiotic consumption.
Qualitative analysis revealed that three out of nine and one out of five studies improved the diversity indices α and β, respectively. However, these were temporary and not substantial enough to recommend probiotics as a therapeutic remedy for dysbiosis.
“The trend of microbiome recovery after a 3-8 week follow-up period regardless of probiotic supplementation and remission differences between the intervention and control groups challenges questions about the benefits of routine probiotic supplementation during antibiotic treatment.”
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