Antibiotics are important clinical tools for treating bacterial infections, yet we recognize that an important side effect of antibiotic use is disruption of the microbial community living in the human gut. Antibiotics targeted against bacterial pathogens generally have the secondary effects of decreasing certain groups of bacteria and lowering gut microbiota diversity. Antibiotics are also associated with harms such as antibiotic associated diarrhea and C. difficile colitis. Probiotics have been shown to mitigate these clinical scenarios, but can probiotics help restore the microbiota?
In a new review paper published in Nature Reviews Gastroenterology & Hepatology, eight scientists comprehensively examined the evidence on using probiotics to restore the gut bacterial community during and after antibiotic treatment. The authors, spanning expertise in clinical medicine, biostatistics, basic microbiome science, and probiotic microbiology, describe current evidence and explore both the potential and limitations of probiotics for mitigating antibiotic disruption of the gut microbiota.
The scientists found a lack of studies that directly address this research question. Current evidence has not addressed if probiotics in general restore the gut microbiota to its pre-antibiotic state. Some studies have shown that certain probiotics can mitigate shifts in microbiome function due to antibiotic use, but data on restoration of microbial composition are relatively rare and suffer from methodological weaknesses that limit their conclusiveness. Other studies have shown that probiotics administered with antibiotics can lead to microbiota changes – not necessarily restoration - which tend to be interpreted by some as beneficial, but the existing lack of clarity around a healthy microbiota composition and how the microbiota adapts to change makes such interpretations subject to dispute.
The lack of conclusive evidence for microbiota restoration does not detract from the existing evidence that specific probiotics can reduce clinical symptoms in individuals taking antibiotics. Namely, certain probiotics are shown in meta-analyses to reduce the risk of antibiotic-associated diarrhea and C. difficile-associated diarrhea, to the extent that they are recommended in a number of clinical guidelines internationally. The mechanisms responsible for these benefits remain unclear, but some effects may occur through the gut microbiota or through direct interactions with gut physiology.
The review's authors state that research in the future should account for the unique effects of each type of antibiotic on the gut microbiota, and should examine how specific probiotic species and strains differently impact gut microbiota restoration. It is likely that no universal probiotic solution exists.
A fundamental complication in interpretation of evidence in this field is the difficulty in defining what, when, and how to measure microbiota disruption and recovery, say the scientists. A variety of different techniques are used from study to study, making evidence difficult to synthesize and conclusions difficult to draw. The scientists suggest that proper assessment of the microbiota should include multiple readouts, such as diversity, both relative and absolute abundance, and host-related parameters. However, even commonly used measures, such as those for taxonomic or functional diversity, have inherent limitations for characterizing restoration. Importantly, these measures are multidimensional, yet are expressed as a single output, which can be shared by two very different microbiota. More fundamentally, we do not know which measures of diversity are most relevant to health.
Lead author Prof. Hania Szajewska MD PhD says, "Restoring gut microbiota with probiotics during antibiotic use is an important topic. Although many studies include microbiome-related endpoints, robust research specifically targeting the restoration of gut microbiota as a primary outcome remains limited. We hope future studies will address this gap to enhance our understanding of the microbiome and the clinical benefits of probiotics."
Co-lead author Prof. Karen Scott PhD says, "Our in-depth examination found very little data to tell us if probiotics can help restore a disturbed gut microbiota. Even though certain probiotics are clearly beneficial when taken alongside antibiotics to prevent negative effects such as antibiotic-associated diarrhea, we still don't know exactly how they achieve this."
The effects of antibiotic treatment on the gut microbiota and on clinical symptoms continue to be investigated. Probiotics may hold promise as a strategy for gut microbiota recovery, but more research is needed to refine our ability to measure microbiota adaptation and recovery, establish goals for microbiota protection or restoration, and define the effective strains and doses for this purpose.
