Prebiotic Type Spotlight: Synbiotic Administration Alongside Antibiotics

Each edition of GPA’s Prebiotic Spotlight focuses on a specific prebiotic type to raise awareness about prebiotics, sources of prebiotics, recent research, and marketplace applications. In this issue, GPA highlights the impacts of antibiotic administration on the gut microbiota, benefits of synbiotic administration alongside antibiotics, and more.

Overview 

Antibiotic treatments, such as amoxicillin, are known to disrupt the gut microbiota, leading to intestinal dysbiosis, decreased microbial diversity and abundance, and reduced production of short-chain fatty acids (SCFAs). These alterations can contribute to gastrointestinal issues, including antibiotic-associated diarrhea (AAD) (Guridi et al, 2020; Merenstein et al, 2021).

After treatment with antibiotics, it is important to support the recovery and repopulation of the gut microbiota. This is an area where probiotics can play a beneficial role (Guridi et al, 2020; Merenstein et al, 2021). Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. They can utilize prebiotics to enhance their beneficial effects (Guridi et al, 2020). When combined, probiotics and prebiotics act synergistically to enhance the health of the host and are collectively referred to as synbiotics. However, there is limited research on the effect of synbiotics in the treatment of antibiotic-induced gut microbiota dysfunctions. The present spotlight highlights the potential of synbiotics to mitigate the negative effects of antibiotics on the gut microbiota.

Antibiotic-induced gastrointestinal dysfunction

Although antibiotics are essential for eliminating pathogenic infections, they lack specificity, and as a result, eradicate both harmful pathogens as well as beneficial microbes in the gut (Dahiya & Nigam, 2023). This leads to an imbalance of pathogens to beneficial gut bacteria, otherwise known as gut dysbiosis (Dahiya & Nigam, 2023). Gut dysbiosis is associated with the development of chronic disease such as obesity and type 2 diabetes as well as inflammatory bowel disease (IBD), colitis, leaky gut syndrome, liver disease, and colorectal cancer (John et al, 2024; Dahiya & Nigam, 2023). Gut dysbiosis may also cause a decreased immune response of the host, inflammation in the gut, and negative impacts on mental health (Dahiya & Nigam, 2023).

Additionally, treatment with antibiotics such as amoxicillin/clavulanate, cephalosporins, and clindamycin are associated with an increased risk of AAD, which occurs in up to 39% of people taking antibiotics. Symptoms of AAD include loose/watery stool, abdominal cramping, urgency, or even severe dehydration and electrolyte imbalance (Liao et al, 2021; Goli et al, 2019; Guridi et al, 2020). Although antibiotic-related gut issues can affect anyone, they are a particular concern for children and those taking antibiotics earlier in life (Dahiya & Nigam, 2023). Given the adverse effects of antibiotic-induced gut dysbiosis, it is essential to correct, if not prevent gut microbiome dysbiosis.

Synbiotics: Synergy with the gut microbiota

It is possible to correct gut microbiome dysbiosis induced by antibiotic treatment by increasing the consumption of prebiotics, probiotics, and synbiotics in the diet (Dahiya & Nigam, 2023). Synbiotics are the combination of prebiotics and probiotics and allow the two to work together to confer health benefit to the host. Recent research suggests that supplementation with synbiotics may be more effective in promoting the growth of gut bacteria, restoring gut microbiota dysfunction, and enhancing diversity of the gut microbiota in obesity, compared to supplementation with probiotics alone (Sergeev et al, 2020). Recent research suggests that supplementation with synbiotic containing probiotics; Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium longum, and Bifidobacterium bifidum (15×109 CFU/capsule), with prebiotic-type galactooligosaccharides (GOS; 5.5 g/day), leads to increased abundance of beneficial gut bacteria such as Bifidobacterium and Lactobacillus compared to a placebo group (Sergeev et al, 2020). Also, recent research used probiotics such as Lactobacillus rhamnosus GG with prebiotics from fructooligosaccharides (FOS) to demonstrate improvements in incidence of AAD (Guiri et al, 2020). Overall, synbiotics may be able to mitigate effects of AAD by restoring the gut microbiota, though the effectiveness depends on the probiotic strain in the synbiotic (Guridi et al, 2020).

Recent Research

Guridi et al (2020) conducted a multicentre, randomized, double-blind, parallel-group, placebo-controlled trial to assess the efficacy of synbiotic supplementation in preventing AAD in adults undergoing antibiotic treatment for oral or dental infections. One hundred and fifty-one adults ages 18-65 years were randomized into two groups: 1) synbiotic group or 2) placebo. Participants consumed their antibiotic 3 times daily, separated by 8 hours, for 7 days and a synbiotic or placebo 2 hours after their morning antibiotic. The antibiotic was Augmentin®, which contained 875 mg of amoxicillin and 125 mg of clavulanic acid. The synbiotic was Prodefen Plus®, which contained 990 mg of fructooligosaccharides (FOS), 7 probiotic strains; 1×1010 CFU Lactobacillus rhamnosus GG; 1×109 CFU, L. casei, S. thermophilus, B. breve, L. acidophilus, B. infantis and B. bulgaricus, per sachet. Study visits took place at baseline, day 7, and day 14. Results suggest that supplementation with Prodefen Plus® synbiotic led to significant reductions in incidence of AAD and a significant improvement in stool consistency, relative to the placebo group. Additionally, in the synbiotic group, the perceived severity of AAD was improved. Overall, supplementation with a synbiotic when undergoing antibiotic treatment may improve antibiotic-associated diarrhea in adults requiring antibiotic treatment.

Jačan et al. (2020) conducted a study to assess the interaction between antibiotic administration with synbiotics on the gut microbiome in murine fecal samples. 8-week-old male mice were randomly assigned to the following groups: placebo or synbiotic was administered for 3 weeks prior to treatment with vehicle or antibiotic for 11 days, or synbiotic administered for a prolonged period, 3 weeks prior and continuing for 12 weeks after treatment with vehicle/antibiotic for 11 days. To simplify, there were four groups: 1) placebo + vehicle, 2) placebo + antibiotic, 3) synbiotic + vehicle, and 4) synbiotic + antibiotic. The synbiotic used was OMNi BiOTiC® STRESS Repair, containing the following bacterial strains: Lactobacillus casei W56, Lactobacillus acidophilus W22, Lactobacillus paracasei W20, Bifdobacterium lactis W51, Lactobacillus salivarius W24, Lactococcus lactis W19, Bifidobacterium lactis W52, Lactobacillus plantarum W62, and Bifdobacterium bifdum W23. The synbiotic was administered via the drinking water of the mice. Antibiotic treatment was delivered via oral gavage and consisted of bacitracin, meropenem, neomycin, and vancomycin. Fecal samples were collected from all groups before and after antibiotic treatment. Microbiome analysis was conducted on fecal samples by a 16S RNA sequencing. Results showed that treatment with antibiotic reduced bacteria richness and diversity. However, synbiotic treatment helped to preserve populations of Lactobacillales and increase Verrucomicrobiales and Bifidobacteriales, when taken 3 weeks prior and during antibiotic treatment. Interestingly, treatment with synbiotics maintained Verrucomicrobiales but not Lactobacillales and Bifidobacteriales when taken for prolonged periods post-antibiotic exposure. Overall, these findings suggest that synbiotics may have protective effects on gut bacteria, particularly when administered before and during antibiotic treatment.

Goli et al (2019) conducted a randomized, double-blind, clinical trial to assess the efficacy of synbiotic supplementation in patients who are being treated with antibiotics on symptoms of AAD. One hundred male and female children ages 2 months to 14 years were randomized into two groups: 1) synbiotic group or 2) control group (receiving starch placebo). All participants began their antibiotic as per protocol and within 24 hours, also began their designated synbiotic or control which was continued for 7 days after their round of antibiotics was complete. The synbiotic contained (Lactobacillus casei, Lactobacillus rhamnosus, Streptococcus thermophilus, Lactobacilus acidophilus, Bifidobacterium breve, Bifidobacterium infantis, Lactbacillus bulgaris). The results suggest that the synbiotic group experienced a lower incidence of AAD compared to the control group, which exhibited a significantly higher risk of AAD. Overall, this study suggests that consuming synbiotics while undergoing antibiotic treatment and for a short period afterwards will help to prevent and reduce risk of AAD in children.

Challenges and Limitations

• • Future research is needed to determine the most effective probiotic strains and prebiotic types to pair with antibiotics for preventing adverse events such as AAD.
  • The variability of individual gut microbiomes, and factors such as age, dietary habits, lifestyle, and history of antibiotic use can influence the response to synbiotic supplementation.
  • Although some studies suggest that taking a synbiotic during and after antibiotic treatment may be beneficial, further research is needed to determine the optimal timing (before, during, or after antibiotic use).
  • Future research is needed on the implications of synbiotics and antibiotics in people with obesity or other pre-existing gut microbiome dysbiosis (Sergeev et al, 2020).
  • The quantity and type of antibiotic used for treatment may affect the severity of AAD and other complications, and therefore an optimal synbiotic formulation may be antibiotic dependent (Guridi et al, 2020).

Conclusions

Although antibiotics are essential for treating infections, they not only eliminate pathogens, but also the existing beneficial bacteria in the gut, which leads to gut dysbiosis and adverse events such as AAD (Dahiya & Nigam, 2023). Additionally, gut dysbiosis has been linked to the development of chronic diseases such as obesity, type 2 diabetes, and others, with children at an increased risk. This highlights the importance of correcting gut microbiome dysbiosis and repopulating the gut with beneficial gut bacteria (Dahiya & Nigam, 2023). Probiotics work in synergy with prebiotics to confer health benefits to the host. Research suggests that probiotics are even more effective when combined with a prebiotic, forming a synbiotic, compared to using a prebiotic alone. Specifically, research suggests that synbiotics may reduce the incidence of AAD in children and adults taking antibiotics (Goli et al, 2019; Guridi et al, 2020). Also, research suggests that synbiotics may reduce the incidence of AAD when taken before, during and after antibiotic treatment (Goli et al, 2019). Although synbiotics have shown promise, there are various limitations in the literature including dose of antibiotic treatment, history of antibiotic use, individual differences in gut microbiota, lifestyle factors, and others. Additionally, further research should confirm the optimal timeline for synbiotic supplementation, strain and type of pro- and prebiotic.