The use of probiotics and prebiotics in decolonizing pathogenic bacteria from the gut; a systematic review and meta-analysis of clinical outcomes

Abstract

Repeated exposure to antibiotics and changes in the diet and environment shift the gut microbial diversity and composition, making the host susceptible to pathogenic infection. The emergence and ongoing spread of AMR pathogens is a challenging public health issue. Recent evidence showed that probiotics and prebiotics may play a role in decolonizing drug-resistant pathogens by enhancing the colonization resistance in the gut. This review aims to analyze available evidence from human-controlled trials to determine the effect size of probiotic interventions in decolonizing AMR pathogenic bacteria from the gut. We further studied the effects of prebiotics in human and animal studies. PubMed, Embase, Web of Science, Scopus, and CINAHL were used to collect articles. The random-effects model meta-analysis was used to pool the data. GRADE Pro and Cochrane collaboration tools were used to assess the bias and quality of evidence. Out of 1395 citations, 29 RCTs were eligible, involving 2871 subjects who underwent either probiotics or placebo treatment to decolonize AMR pathogens. The persistence of pathogenic bacteria after treatment was 22%(probiotics) and 30.8%(placebo). The pooled odds ratio was 0.59(95% CI:0.43-0.81), favoring probiotics with moderate certainty (p = 0.0001) and low heterogeneity (I² = 49.2%, p = 0.0001). The funnel plot showed no asymmetry in the study distribution (Kendall'sTau = -1.06, p = 0.445). In subgroup, C. difficile showed the highest decolonization (82.4%) in probiotics group. Lactobacillus-based probiotics and Saccharomyces boulardii decolonize 71% and 77% of pathogens effectively. The types of probiotics (p < 0.018) and pathogens (p < 0.02) significantly moderate the outcome of decolonization, whereas the dosages and regions of the studies were insignificant (p < 0.05). Prebiotics reduced the pathogens from 30% to 80% of initial challenges. Moderate certainty of evidence suggests that probiotics and prebiotics may decolonize pathogens through modulation of gut diversity. However, more clinical outcomes are required on particular strains to confirm the decolonization of the pathogens. Protocol registration: PROSPERO (ID = CRD42021276045).

Keywords: Probiotics; alpha diversity; decolonization; gut microbiota; prebiotics.

Graphical abstract

Figure 1.

PRISMA flow diagram showing the systematic review process with the bibliometric assessment, including article attrition and study selection.

Figure 2.

Forest plot for the intervention group (probiotics) vs. placebo for the decolonization success at the end of the study or at a 1-month time point. The I² values are interpreted as low, moderate, and high levels of heterogeneity, where I² = 0–49%, I²= 50–75%, and I² > 75%.^, A 5% significance level (p<0.05) was used to determine the significant difference between the treatment efficacies. The events consist of the persistence of bacteria.

Figure 3.

Forest plot of the sub-group analysis for the efficacy of probiotics concomitant with or without conventional medicine. The I² values are interpreted as low, moderate, and high levels of heterogeneity, where I² = 0–49%, I²= 50–75%, and I²> 75%, respectively.^, A 5% significance level (p<0.05) was used to determine the significant difference between the treatment efficacies. The events consist of the persistence of bacteria.

Figure 4.

Forest plot of the sub-group analysis for the efficacy of specific probiotics Lactobacillus, Mixed probiotics, S. boulardii, and other probiotics vs placebo. The I² values are interpreted as low, moderate, and high levels of heterogeneity, where I² = 0–49%, I²= 50–75%, and I²> 75%, respectively.^, A 5% significance level (p<0.05) was used to determine the significant difference between the treatment efficacies. The events consist of the persistence of bacteria.

Figure 5.

Forest plots for sub-group analysis of the efficacy of the intervention (Probiotics) vs. Placebo on C. difficile, MDR-Enterobacteriaceae, VRE, and H. pylori. The I² values are interpreted as low, moderate, and high levels of heterogeneity, where I² = 0–49%, I²= 50–75%, and I²> 75%, respectively.^, A 5% significance level (p<0.05) was used to determine the significant difference between the treatment efficacies. The events consist of the persistence of bacteria.

Figure 6.

Results of the meta-regression of the covariates, dosages of probiotics, and types of probiotics and types of bacteria on the decolonization of pathogens.

Figure 7.

Funnel plot of comparison: efficacy of pathogenic bacteria decolonization.