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The Cochrane Database of Systematic... Apr 2019Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antibiotics alter the microbial balance commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action.
OBJECTIVES
The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children.
SEARCH METHODS
MEDLINE, Embase, CENTRAL, CINAHL, and the Web of Science (inception to 28 May 2018) were searched along with registers including the ISRCTN and Clinicaltrials.gov. We also searched the NICE Evidence Services database as well as reference lists from relevant articles.
SELECTION CRITERIA
Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Study selection, data extraction, and risk of bias assessment were conducted independently by two authors. Dichotomous data (incidence of AAD, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea) as mean difference (MD), along with corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. For studies reporting on microbiome characteristics using heterogeneous outcomes, we describe the results narratively. The certainty of the evidence was evaluated using GRADE.
MAIN RESULTS
Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. The risk of bias was determined to be high in 20 studies and low in 13 studies. Complete case (patients who did not complete the studies were not included in the analysis) results from 33 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control.After 5 days to 12 weeks of follow-up, the incidence of AAD in the probiotic group was 8% (259/3232) compared to 19% (598/3120) in the control group (RR 0.45, 95% CI 0.36 to 0.56; I² = 57%, 6352 participants; NNTB 9, 95% CI 7 to 13; moderate certainty evidence). Nineteen studies had loss to follow-up ranging from 1% to 46%. After making assumptions for those lost, the observed benefit was still statistically significant using an extreme plausible intention-to-treat (ITT) analysis, wherein the incidence of AAD in the probiotic group was 12% (436/3551) compared to 19% (664/3468) in the control group (7019 participants; RR 0.61; 95% CI 0.49 to 0.77; P <0.00001; I² = 70%). An a priori available case subgroup analysis exploring heterogeneity indicated that high dose (≥ 5 billion CFUs per day) is more effective than low probiotic dose (< 5 billion CFUs per day), interaction P value = 0.01. For the high dose studies the incidence of AAD in the probiotic group was 8% (162/2029) compared to 23% (462/2009) in the control group (4038 participants; RR 0.37; 95% CI 0.30 to 0.46; P = 0.06; moderate certainty evidence). For the low dose studies the incidence of AAD in the probiotic group was 8% (97/1155) compared to 13% (133/1059) in the control group (2214 participants; RR 0.68; 95% CI 0.46 to 1.01; P = 0.02). Again, assumptions for loss to follow-up using an extreme plausible ITT analysis was statistically significant. For high dose studies the incidence of AAD in the probiotic group was 13% (278/2218) compared to 23% (503/2207) in control group (4425 participants; RR 0.54; 95% CI 0.42 to 0.70; P <0.00001; I² = 68%; moderate certainty evidence).None of the 24 trials (4415 participants) that reported on adverse events reported any serious adverse events attributable to probiotics. Adverse event rates were low. After 5 days to 4 weeks follow-up, 4% (86/2229) of probiotics participants had an adverse event compared to 6% (121/2186) of control participants (RD 0.00; 95% CI -0.01 to 0.01; P < 0.00001; I² = 75%; low certainty evidence). Common adverse events included rash, nausea, gas, flatulence, abdominal bloating, and constipation.After 10 days to 12 weeks of follow-up, eight studies recorded data on our secondary outcome, the mean duration of diarrhea; with probiotics reducing diarrhea duration by almost one day (MD -0.91; 95% CI -1.38 to -0.44; P <0.00001; low certainty evidence). One study reported on microbiome characteristics, reporting no difference in changes with concurrent antibiotic and probiotic use.
AUTHORS' CONCLUSIONS
The overall evidence suggests a moderate protective effect of probiotics for preventing AAD (NNTB 9, 95% CI 7 to 13). Using five criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate the subgroup effect based on high dose probiotics (≥ 5 billion CFUs per day) was credible. Based on high-dose probiotics, the NNTB to prevent one case of diarrhea is 6 (95% CI 5 to 9). The overall certainty of the evidence for the primary endpoint, incidence of AAD based on high dose probiotics was moderate due to the minor issues with risk of bias and inconsistency related to a diversity of probiotic agents used. Evidence also suggests that probiotics may moderately reduce the duration of diarrhea, a reduction by almost one day. The benefit of high dose probiotics (e.g. Lactobacillus rhamnosus orSaccharomyces boulardii) needs to be confirmed by a large well-designed multi-centered randomized trial. It is premature to draw firm conclusions about the efficacy and safety of 'other' probiotic agents as an adjunct to antibiotics in children. Adverse event rates were low and no serious adverse events were attributable to probiotics. Although no serious adverse events were observed among inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit, observational studies not included in this review have reported serious adverse events in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.
Topics: Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Diarrhea; Female; Humans; Infant; Infant, Newborn; Male; Probiotics; Treatment Outcome
PubMed: 31039287
DOI: 10.1002/14651858.CD004827.pub5 -
Nutrients Nov 2022Prebiotic and probiotic supplementation and yogurt consumption (a probiotic food) alter gut microbial diversity, which may influence colorectal carcinogenesis. This... (Review)
Review
Prebiotic and probiotic supplementation and yogurt consumption (a probiotic food) alter gut microbial diversity, which may influence colorectal carcinogenesis. This systematic review evaluates the existing literature on the effect of these nutritional supplements and yogurt consumption on colorectal neoplasia incidence among adults. We systematically identified ten randomized controlled trials and observational studies in adults age ≥ 18 without baseline gastrointestinal disease. Prebiotics included inulin, fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, isomaltooligosaccharides, and β-glucans. Probiotics included bacterial strains of Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Bacillus, Pediococcus, Leuconostoc, and Escherichia coli. Synbiotic supplements, a mixture of both prebiotic and probiotic supplements, and yogurt, a commonly consumed dietary source of live microbes, were also included. We defined colorectal neoplasia as colorectal adenomas, sessile serrated polyps, and colorectal cancer (CRC). Overall, findings suggest a moderate decrease in risk of adenoma and CRC for high levels of yogurt consumption compared to low or no consumption. Prebiotic supplementation was not associated with colorectal neoplasia risk. There was some evidence that probiotic supplementation may be associated with lower risk of adenomas but not with CRC incidence. Higher yogurt consumption may be associated with lower incidence of colorectal neoplasia. We found little evidence to suggest that prebiotic or probiotic supplements are associated with significant decreases in CRC occurrence.
Topics: Humans; Prebiotics; Yogurt; Synbiotics; Probiotics; Colorectal Neoplasms
PubMed: 36432622
DOI: 10.3390/nu14224937 -
BMC Infectious Diseases Jan 2019Previous studies demonstrated that the diversity and composition of respiratory microbiota in TB patients were different from healthy individuals. Therefore, the aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies demonstrated that the diversity and composition of respiratory microbiota in TB patients were different from healthy individuals. Therefore, the aim of the present analysis was to estimate the relative proportion of respiratory microbiota at phylum and genus levels among TB cases and healthy controls.
METHODS
The PubMed and Google Scholar online databases were searched to retrieve relevant studies for the analysis. The statistical analysis was done using STATA version 11, pooled estimates are presented using graphs. The summary of findings in included studies is also presented in Table 1.
RESULTS
The phylum level analysis shows that the pooled proportions of Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria, and Crenarchaeota were determined among tuberculosis patients and healthy controls. In brief, Firmicutes, and Proteobacteria were the most abundant bacterial phyla in both TB cases and healthy controls, composing 39.9 and 22.7% in TB cases and 39.4 and 19.5% in healthy controls, respectively. The genus level analysis noted that Streptococcus (35.01%), Neisseria (27.1%), Prevotella (9.02%) and Veillonella (7.8%) were abundant in TB patients. The Prevotella (36.9%), Gammaproteobacteria (22%), Streptococcus (19.2%) and Haemophilus (15.4%) were largely seen in healthy controls. Interestingly, Veillonella, Rothia, Leuconostoc were unique to TB cases, whereas Lactobacillus, and Gammaproteobacteria, Haemophilus, and Actinobacillus were identified only in healthy controls.
CONCLUSION
The composition of the respiratory microbiota in TB patients and healthy controls were quite different. More deep sequencing studies are needed to explore the microbial variation in the respiratory system in connection with TB.
Topics: Bacteria; Humans; Microbiota; Respiratory System; Tuberculosis, Pulmonary
PubMed: 30683056
DOI: 10.1186/s12879-019-3712-1