Alterations in the bacterial component of the microbiota, most often due to the use of antibiotics, can lead to ecological changes and growth of Clostridium difficile – recently renamed Clostridioides difficile.
C.difficile is responsible for the most severe cases in 10%-25% of all episodes of AAD, which may lead to electrolyte disturbances, pseudo-membranous colitis, toxic megacolon and, rarely, death. Clinical manifestations of C difficile can range from an asymptomatic carrier state to mild CDI to severe, fulminant, life-threatening infection.
How antibiotics affect the gut
Many factors, including drug dose, route of administration, absorption, and host inactivation, dictate the intensity of antibiotic effects on the gut microbiota. The normal microflora acts as a barrier against colonisation of potentially pathogenic microorganisms and against overgrowth of already present opportunistic microorganisms.
Antibiotics such as broad-spectrum b-lactams, glycopeptides and fluoroquinolones that act on anaerobes are most commonly linked to AAD. Mild cases have no established therapy, and are customarily treated with discontinuation of the antibiotic, supportive care, and dietary changes. However, serious cases often require bed rest, intravenous fluids, and additional antibiotics such as metronidazole or vancomycin, and may relapse in almost 25% patients.
Can probiotics prevent AAD?
The core benefit of probiotics is exercised by contributing to the maintenance of a balanced microbiota and therefore by creating a favourable gut environment. Furthermore, probiotics support the health of the GI tract and the immune system.
The rationale for the use of probiotics is based on the assumption that AAD results from the disruption of the commensal gut microbiota caused by antibiotic therapy. A recent review by Goodman et al (2021) found that probiotics are effective for preventing AAD. Probiotics are defined as live micro-organisms that, when administered in adequate amounts, confer a health benefit on the host.
Several studies have shown that probiotics improve the microbial balance of the host and reduce colonisation by pathogenic bacteria. They can be delivered orally, are thought to adhere to target GI epithelium and are stable in acid and bile.
Several mechanisms are proposed to contribute to the protective effect of probiotics against AAD. Antibiotics are known to disrupt the complex balance of gastrointestinal microbiota, allowing colonisation by pathogenic organisms such as C. difficile.
Probiotics are believed to temporarily colonise the gut, producing bactericidal acids and peptides, and competing for nutrients and epithelial adhesion.
Several species of the Lactobacillus genus are acid producing, lower environmental pH, and secrete exotoxins that inhibit pathogenic bacterial growth and inhibit binding of enterotoxins to gut epithelium, suggesting that probiotics may be the panacea (a solution or remedy for all difficulties or diseases) to AAD.
The team conducted a systematic review and meta-analysis of randomised controlled trials to evaluate existing evidence for the use of probiotics in preventing AAD in adults.
Forty-two studies (n=11 305 participants) were included in this review. The pooled analysis suggests that co-administration of probiotics with antibiotics reduces the risk of AAD in adults by 37%.
Efficacy and safety are strain specific
According to Goodman et al, subgroup analyses comparing high and low dose of the same probiotic demonstrated a positive protective effect, and only certain species, mainly of the Lactobacillus and bifidobacterial genera, were found to be effective. Studies with a low baseline AAD risk did not show any difference in risk but studies with moderate or high baseline AAD risk demonstrated a significant risk reduction.3
Lactobacillus reuteri recently renamed Limosilactobacillus reuteri (L. reuteri) is a Gram-positive bacterium that naturally inhabits the gut of mammals. First described in the early 1980s, it has been safely used in infants and adults to manage of GI symptoms such as gut infections, Helicobacter pylori eradication, AAD, constipation inflammatory bowel syndrome, inflammatory bowel disease, and colorectal cancer.4
It can reduce abdominal pain in infantile colic, the functional abdominal discomfort in children, and it can decrease crying due to necrotizing enterocolitis in preterm neonates and can improve gut motility and chronic constipation as demonstrated in infants.4
L. reuteri can colonise different human body sites, including primarily the GI tract. It adheres to the intestinal epithelium, producing proteins able to bind with the mucus, making it tough for pathogen microorganisms to enter, and thereby remodelling the balanced composition of gut microbiota.
Moreover, L. Reuteri produces antimicrobial molecules and promotes the development and the functionality of regulatory T cells, strengthening the gut barrier, and decreasing the microbial translocation from the intestinal lumen to the tissue.
Choosing an appropriate probiotic is challenging
The choice of an appropriate probiotic is multi-factored, based on the mode and type of disease indication and the specific efficacy of probiotic strain(s), as well as product quality and formulation.
Table 1: Clinical decision algorithm for choosing an appropriate probiotic product
Conclusion
In conclusion, L. reuteri plays a key role in maintaining a balanced microbiota gut composition. Many clinical trials have proved the safety, efficacy, and tolerance of this probiotic in preventing and treating numerous GI disorders, ranging from diarrhoea to constipation. Its efficacy and safety in the prevention of AAD has also been shown, leading researchers to conclude the probiotics may be the solution to AAD.
REFERENCES:
1. Cai J, Zhao C, Du Y, et al. Comparative efficacy, and tolerability of probiotics for antibiotic-associated diarrhea: Systematic review with network meta-analysis. EUG Journal, 2018.
2. Goodman C, Keating G, Georgousopoulou E, Hespte C and Levett K. Probiotics for the prevention of antibiotic-associated diarrhoea: a systematic review and meta-analysis. BMJ Open, 2021.
3. Koldziej M and Szajewska H. Lactobacillus reuteri DSM 17938 in the prevention of antibiotic-associated diarrhoea in children: protocol of a randomised controlled trial. BMJ Open, 2017.
4. Sniffen JC, McFarland LV, Evans CT, and Goldstein EJC. Choosing an appropriate probiotic product for your patient: An evidence-based practical guide. PLOSOne, 2018.
5. Walk ST and Young VB. Emerging Insights into Antibiotic-Associated Diarrhea and Clostridium difficile Infection through the Lens of Microbial Ecology. Interdisciplinary Perspectives on Infectious Diseases, 2008.
