Antibiotics kill off pathogens, saving untold numbers of lives every year. Unfortunately, the 20th century wonder drugs also destroy a lot of beneficial bacteria along the way. The ensuing disturbances in gut microbiota communities can lead to diarrhea and other displays of dysbiosis.
Antibiotics disrupt gut microbiota
When antibiotics are administered, dysbiosis may occur rapidly, within days, leading to altered bacterial metabolism and impaired host proteome in mice and humans.
Many studies confirm that antibiotic exposure alters the gut microbiome in children and adults.
In a 2021 review of 12 studies in children, antibiotic exposure was associated with reduced microbiome diversity and richness, and with changes in bacterial abundance. Significant reductions were seen in bifidobacteria (5 studies) and lactobacilli (2 studies), and significant increases in Proteobacteria such as E. coli (4 studies). Different antibiotics exerted different effects on the microbiota. For example, macrolide (e.g. azithromycin) exposure was associated with reduced richness for twice as long as penicillin.
With adults, in a small study of 12 healthy men over a 6-month period following a 4-day intervention with a cocktail of three antibiotics, initial changes included blooms of enterobacteria and other pathobionts, and the depletion of Bifidobacterium species and butyrate producers.
Importantly, a study of 1413 individuals revealed that the use of antimicrobial drugs is associated with a long-term shift in the composition of the gut microbiota — up to four years in some individuals. These effects differ in strength and duration, depending on the antimicrobial drug group used. Differential effects on gut microbiota should be considered by practitioners when prescribing antibiotics.
Probiotics and antibiotics
Antibiotics create a vacancy for opportunistic pathogens to move in or expand. Beneficial organisms are pushed out. The takeover happens fast and can last a long time.
Supplementation with probiotics to offset the effects of antibiotics has become popular.
Restoring the beneficial bacteria has been shown to help reduce the incidence and duration of antibiotic-associated diarrhea (AAD.)
Meta-analysis of 25 randomized controlled trials (RCTs) reported that a variety of different types of probiotics significantly reduced the development of AAD.
There is also evidence from a review of 33 studies (6352 participants) that probiotics (including Bacillus spp., Bifidobacterium spp., Clostridium butyricum, lactobacilli, Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., or Streptococcus spp., alone or in combination.) may confer a moderate protective effect of probiotics for reducing the risk of AAD.
Clostridium difficile (C. difficile) is a notorious and sometimes deadly opportunistic pathogen frequently acquired with antibiotic use. Based on a meta-analysis of 31 randomized controlled trials including 8672 adults and children, evidence suggests that probiotics reduce the risk of C. difficile‐associated diarrhea by 60%.
Moreover, probiotics prescribed with antibiotics resulted in better treatment outcomes than with antibiotics alone in disorders including Helicobacter pylori infections, small intestinal bacterial overgrowth (SIBO) as well as other gut infections.
Incidentally, a meta-analysis of 17 RCTs demonstrated that infants and children who received probiotics (single or combination lactobacilli and bifidobacteria delivered in a range of food or supplement products) to prevent acute illnesses had a lower risk of being prescribed antibiotics, relative to those who received placebo. Reducing antibiotic use is a public health goal, given antibiotic resistance and the collateral damage.
Probiotics: with antibiotics or after the course?
Few studies looked at how timing of probiotic administration compared in regard to antibiotic use. However, in a 2021 study of 55 full-term neonates,antibiotic exposure was found to dramatically alter gut microbiota, with a significant decrease of bifidobacteria and lactobacilli. The use of probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) simultaneously with the antibiotics was found to be beneficial for the gut microbiota as compared to delaying the use of probiotics to follow treatment with antibiotics, particularly in promoting the abundance of Bifidobacterium.
Are probiotics protected from antibiotics?
Newer technologies including biofilm-inspired encapsulation may protect the probiotics from antibiotic action, enabling concurrent usage with optimum effect.
Takeaway
Not surprisingly, antibiotics disturb the gut microbiota balance as they target and eradicate pathogens. Fortunately, the use of probiotics may counteract some of those deleterious effects (different depending on the antimicrobial drug group used.) Probiotics may help reshape the microbial flora as it repopulates. And as always, that potential is specific to the strain (combination) of probiotics.
Key References
Ferrer, Manuel et al. “Gut microbiota disturbance during antibiotic therapy: a multi-omic approach.” Gut microbes vol. 5,1 (2014): 64-70. doi:10.4161/gmic.27128
García-Collinot, Grettel et al. “Effectiveness of Saccharomyces boulardii and Metronidazole for Small Intestinal Bacterial Overgrowth in Systemic Sclerosis.” Digestive diseases and sciences vol. 65,4 (2020): 1134-1143. doi:10.1007/s10620-019-05830-0
Goldenberg, Joshua Z et al. “Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children.” The Cochrane database of systematic reviews vol. 12,12 CD006095. 19 Dec. 2017, doi:10.1002/14651858.CD006095.pub4
Guo, Qin et al. “Probiotics for the prevention of pediatric antibiotic-associated diarrhea.” The Cochrane database of systematic reviews vol. 4,4 CD004827. 30 Apr. 2019, doi:10.1002/14651858.CD004827.pub5
King, Sarah et al. “Does probiotic consumption reduce antibiotic utilization for common acute infections? A systematic review and meta-analysis.” European journal of public health vol. 29,3 (2019): 494-499. doi:10.1093/eurpub/cky185
McDonnell, Lucy et al. “Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis.” Gut microbes vol. 13,1 (2021): 1-18. doi:10.1080/19490976.2020.1870402
McFarland, Lynne V. “Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease.” The American journal of gastroenterology vol. 101,4 (2006): 812-22. doi:10.1111/j.1572-0241.2006.00465.x
Mulder, M et al. “Long-term effects of antimicrobial drugs on the composition of the human gut microbiota.” Gut microbes vol. 12,1 (2020): 1795492. doi:10.1080/19490976.2020.1791677
Palleja, Albert et al. “Recovery of gut microbiota of healthy adults following antibiotic exposure.” Nature microbiology vol. 3,11 (2018): 1255-1265. doi:10.1038/s41564-018-0257-9
Suez, Jotham et al. “Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT.” Cell vol. 174,6 (2018): 1406-1423.e16. doi:10.1016/j.cell.2018.08.047
Wang, Fan et al. “Probiotics in Helicobacter pylori eradication therapy: Systematic review and network meta-analysis.” Clinics and research in hepatology and gastroenterology vol. 41,4 (2017): 466-475. doi:10.1016/j.clinre.2017.04.004
Zhong, Hui et al. “Impact of probiotics supplement on the gut microbiota in neonates with antibiotic exposure: an open-label single-center randomized parallel controlled study.” World journal of pediatrics : WJP, 10.1007/s12519-021-00443-y. 31 Jul. 2021, doi:10.1007/s12519-021-00443-y