Probiotic therapeutics: A critical review of mechanisms, clinical efficacy, and the frontier of precision microbiome modulation.

This meta-analysis aims to quantitatively assess the incidence and risk factors of both antibiotic-associated diarrhea (AAD) and Clostridioides difficile-associated diarrhea (CDAD) in critically ill patients. We searched Cochrane Library, Web of Science, Embase, PubMed, CNKI, and Wanfang until February 2025. Studies were screened, extracted, and assessed using the Newcastle-Ottawa Scale and GRADE. Analyses used RevMan 5.4 and Stata 15. This meta-analysis revealed an overall incidence of AAD of 29% (95% CI = 24%-35%) in critically ill patients. The following 16 independent risk factors were identified: age (MD = 4.81, 95% CI = 2.85-6.78), male (OR = 1.23, 95% CI = 1.04-1.45),hypertension (OR = 1.86, 95% CI = 1.51-2.29), diabetes (OR = 1.42, 95% CI = 1.11-1.82), cephalosporin (OR = 1.67, 95% CI = 1.31-2.12), glycopeptide antibiotic (OR = 1.48, 95% CI = 1.10-1.98), antifungal agent (OR = 2.55, 95% CI = 1.90-3.41), β-lactam plus enzyme inhibitor (OR = 2.38, 95% CI = 1.86-3.06), proton pump inhibitor (OR = 0.56, 95% CI = 0.37-0.85), probiotic (OR = 1.69, 95% CI = 1.20-2.36), combined antibiotic use (OR = 2.44, 95% CI = 1.96-3.04), gastrointestinal surgery (OR = 2.00, 95% CI = 1.20-3.34), parenteral nutrition (OR = 1.60, 95% CI = 1.18-2.16), duration of antibiotic use (MD = 4.15, 95% CI = 2.93-5.37), APACHE II score (MD = 1.10, 95% CI = 0.55-1.65), and length of ICU stay (MD = 7.02, 95% CI = 4.39-9.66). Additionally, the incidence of CDAD was 12% (95% CI = 7%-17%), with risk factors including enteral nutrition (OR = 2.11, 95% CI = 1.37-3.24), mechanical ventilation (OR = 1.61, 95% CI = 1.12-2.33), carbapenem antibiotic (OR = 1.71, 95% CI = 1.07-2.75), kidney disease (OR = 1.74, 95% CI = 1.04-2.90),and diabetes (OR = 1.83, 95% CI = 1.05-3.21). These findings help identify high-risk patients and guide AAD and CDAD prevention in critical care.

Severe pneumonia in paediatric patients typically necessitates prolonged courses of antibiotic therapy, a practice that elevates vulnerability to antibiotic-associated diarrhoea (AAD). The present study aimed to evaluate the clinical profiles of paediatric patients with AAD secondary to severe pneumonia and to explore evidence-based nursing interventions for this complication. A retrospective cohort. This study was conducted at a tertiary hospital in China, enrolling paediatric patients diagnosed with severe pneumonia. To identify independent risk factors for AAD development, a stepwise analytical framework was applied, comprising univariate analysis, correlation analysis and multivariate logistic regression modelling. A total of 306 children with severe pneumonia were included. The overall incidence of secondary AAD among this cohort was 13.73% (42/306). The median time from antibiotic initiation to AAD onset was 5 days (IQR 3-8 days). Multivariate logistic regression analysis identified five independent risk factors for AAD: age < 1 year (odds ratio [OR] = 2.246, 95% confidence interval [CI]: 1.821-2.909), administration of penicillin-class antibiotics (OR = 2.474, 95% CI: 2.043-3.061), antibiotic treatment duration ≥ 1 week (OR = 2.970, 95% CI: 2.127-3.507), requirement for mechanical ventilation (OR = 3.049, 95% CI: 2.895-3.725), and hospital stay > 14 days (OR = 1.954, 95% CI: 1.630-2.402). In contrast, prophylactic probiotic administration was identified as a protective factor against AAD (OR = 0.801, 95% CI: 0.586-0.944). In clinical practice, stratified management protocols should be implemented for paediatric populations at high risk of AAD. Core components of such protocols include optimising antibiotic selection and treatment duration, initiating early combined probiotic interventions and enhancing intestinal function monitoring.

3'-Sialyllactose (3'-SL) is a naturally occurring prebiotic in milk, known to regulate intestinal microbiota and prevent diseases. However, the mechanisms through which 3'-SL alleviates antibiotic-associated diarrhea remain poorly understood. In this study, an antibiotic-associated diarrhea model was established through the co-administration of ampicillin and neomycin. The effects of 3'-SL supplementation on diarrhea phenotype, inflammation, intestinal permeability, and barrier function were examined in antibiotic-associated diarrhea-model mice. Moreover, gut microbiota composition, metabolite profiles, and their alterations were analyzed using genomic and metabolomic approaches. The results demonstrate that 3'-SL increased body weight and aquaporin (AQP) 3 and AQP4 levels but reduced diarrhea rate, cecal mass, and fecal water content in the model mice, indicating its therapeutic effect on diarrhea. Furthermore, 3'-SL reduced serum levels of IL-6, tumor necrosis factor (TNF)-α, and IL-1β, while increasing IL-10 levels in the mice. Moreover, 3'-SL reduced intestinal permeability by enhancing both the mechanical barrier (ZO-1 and occludin mRNA expression) and the chemical barrier (MUC2 mRNA and protein expression) in the mice. 16S rRNA analysis revealed that mice in the 3'-SL group exhibited greater abundances of Akkermansia, Bacteroides, and Dubosiella, along with a reduced relative abundance of the diarrhea-associated bacterium Alloprevotella. Furthermore, metabolomics analysis indicated that 3'-SL promoted enrichment of purine metabolism, pyrimidine metabolism, nucleotide metabolism, and the pentose phosphate pathway, which may be associated with diarrhea development, inflammation amelioration, and barrier regulation. In conclusion, our findings suggest that 3'-SL ameliorates antibiotic-associated diarrhea by modulating gut microbiota and metabolite profiles.

ZBTB16 controls the onset of Clostridium difficile colitis through the Pyrin inflammasome.

Clostridioides difficile infection (CDI) is recognized as the leading cause of antibiotic-associated diarrhea. There are several case reports of C. difficile enteritis in patients who have undergone colectomy and end ileostomy or ileal pouch-anal anastomosis. This case report describes a unique case of recurrent C. difficile enteritis following proctocolectomy and ileoanal pouch, treated successfully with faecal microbiota transplantation (FMT) via anterograde and retrograde delivery into the small bowel.

Irritable bowel syndrome (IBS) is a chronic functional disorder characterised by abdominal pain and altered bowel habits. The most prevalent subtype is diarrhoea-predominant IBS (IBS-D). The combination of Bacillus subtilis HU58 and Heyndrickxia faecalis (formerly Bacillus coagulans) SC208 has previously exerted positive effects in people with antibiotic-associated diarrhoea and infective diarrhoea. The present multicentre study conducted in India aimed to evaluate the effectiveness and safety of the dual-strain probiotic in adults (18-65 years) with IBS-D. In this randomised, double-blind, placebo-controlled pilot study, 61 participants were recruited and assessed for changes in abdominal pain intensity (Numeric Rating Scale, NRS) and stool consistency (Bristol Stool Form Scale, BSFS) over a 4-week intervention period, with secondary outcomes including responder rates for IBS Global Assessment of Improvement (IBS-GAI) and perceived stress (Perceived Stress Scale, PSS). The probiotic group showed significantly higher overall responder rates for both abdominal pain and stool consistency ( P = 0.003) compared to the placebo group. Significant improvements were observed in abdominal pain ( P = 0.003) and stool consistency ( P = 0.035) scores in the probiotic versus placebo group from baseline to end of intervention. IBS-GAI responder rates were significantly higher among the probiotic versus placebo group ( P = 0.017) whilst perceived stress scores did not differ significantly between groups. In conclusion, supplementation with B. subtilis HU58 and H. faecalis SC208 for 4 weeks was safe and effective in improving stool consistency and abdominal pain in individuals with IBS-D, supporting its potential for symptom management in IBS-D. The trial is registered at https://ctri.nic.in/Clinicaltrials (CTRI/2022/07/044154).

Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. One of the most common uses of probiotics is for prevention of antibiotic-associated diarrhea (AAD). Here we report on the PLAY-ON study (Probiotics: Live and Active Yogurt Cultures for Healthy Children ON Antibiotics) which was a randomized, placebo-controlled, double-blinded study in healthy children who were prescribed antibiotics for acute outpatient upper respiratory illnesses, such as bacterial sinusitis or streptococcal pharyngitis. The treating clinician determined the antibiotic, its dosage and duration. Participants received either a control yogurt or a yogurt containing the probiotic, Bifidobacterium animalis subsp. lactisBB-12. Our primary aim was to determine whether the probiotic prevented AAD. The microbiome of participants was examined longitudinally. Diarrhea rates were nearly identical at 2% (3 cases in the active group, 2 cases in the control group); adverse events were also similar between groups. Thus, our study did not find any differences in the incidence of AAD between those who took the probiotic and the control group. The microbiota of both groups returned to baseline by day 14 and assessment of the microbiome showed no difference in levels or types of antibiotic resistance genes. Broad-spectrum antibiotics are associated with higher rates of adverse events, including AAD, than narrow-spectrum antibiotics, as observed in children taking antibiotics for respiratory tract infections3,4.However, if the antibiotic does not significantly disturb the microbiota there may be no discernable role for the probiotic. This hypothesis is supported by the participants who used broad spectrum penicillins had a significantly higher rate of diarrhea compared to narrow spectrum antibiotic users, 9.1% and 0.51% respectively, (p=0.004)This study suggests that prescribing short-course, narrow spectrum antibiotics can reduce microbiome disruptions, concomitant AAD, and the need for probiotic intervention. . The antibiotics used in our study did not disrupt the microbiome to the extent expected, which likely accounted for the low observed incidence of AAD. Importantly, this observation can inform clinicians’ choice of antibiotic, steering them toward equally therapeutic antibiotics that are less disruptive to the microbiota and better tolerated. Although probiotics are often recommended to prevent AAD, our study demonstrates that in the absence of microbiome disruption, they may not provide benefit.

Probiotics are currently widely used in clinical practice to prevent and treat a wide range of diseases. The purpose of our review is to highlight what we consider to be the most significant clinical studies on the use of probiotics for preventing antibiotic-associated diarrhea, clostridial diarrhea and pseudomembranous colitis. The article also presents the results of studies confirming the efficacy of probiotics in Helicobacter pylori eradication therapy. The review focuses on Linex® Forte, medicinal product containing the combination of Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12).

Antibiotic-associated diarrhea is a common complication of antibiotic therapy that requires timely prevention and high-quality pharmaceutical care to prevent dysbiotic disorders, digestive disorders, and pseudomembranous colitis. Aim. To determine the level of awareness of practicing pharmacists and senior students of pharmacy faculties about antibiotic-associated diarrhea, methods of its prevention, and the main approaches to providing proper pharmaceutical care. Materials and methods. The study was based on the results of an online survey conducted between November 1 and 29, 2024, among pharmacists and senior students, and it aimed to determine the average level of knowledge about the etiopathogenesis, prevention of antibiotic-associated diarrhea, and identify topics that were most difficult to understand or require additional training. The methods used included sociological surveys, comparative analysis, graphical analysis, and analytical and generalizing analysis. Results and discussion. A total of 80 respondents participated in the survey. Of them, 50 % worked as pharmacists; 12.5 % were not employed in a pharmacy at the time of the study; and 37.5 % worked as pharmacy assistants or intern pharmacists. At the same time, 37.5 % of respondents had less than a year of experience, 25 % already worked from one and five years, 25 % worked for more than five years, and 12.5 % had no experience; the latter group consisted of students from the Pharmacy Faculty. The analysis of the respondents’ self-assessment of their knowledge indicates a lack of awareness of the mechanisms of antibiotic-associated diarrhea, modern approaches to its prevention and the rational choice of accompanying agents, particularly probiotics, prebiotics and enterosorbents. The respondents mainly emphasized the importance of studying the treatment and prevention of antibiotic-associated diarrhea, in particular among students of the Pharmacy Faculty. Conclusions. It has been determined that antibiotic-associated diarrhea is a relevant issue for pharmaceutical professionals since patients regularly visit pharmacies with related queries. A survey of pharmaceutical workers of various skill levels and work experience has shown that most respondents are aware of the importance of this issue and the need to improve their knowledge of its treatment and prevention. The results obtained confirm the importance of expanding and deepening the study of antibiotic-associated diarrhea in pharmacy faculty education programs, in order to improve the quality of pharmaceutical care for patients.

Antibiotic-associated diarrhea (AAD) is a self-limiting disorder triggered by antibiotic therapy in pediatric populations. Although multiple probiotics are clinically employed for AAD management, the therapeutic efficacy of Clostridium butyricum (C. butyricum) in pediatric AAD and its underlying mechanisms remain poorly characterized. This study aimed to establish a juvenile mice model of AAD and investigate the therapeutic potential of oral C. butyricum administration in juvenile mice subjected to continuous antibiotics exposure. We systematically assessed pathological changes in colonic tissue, colitis severity, intestinal epithelial barrier integrity, fecal metabolomic profiles, and gut microbiota diversity. Our analysis demonstrates that C. butyricum ameliorates intestinal inflammation, enhances barrier function by modulating the gut microbiota and its metabolites, and significantly alleviates diarrhea symptoms in juvenile AAD mice. Collectively, these findings indicate that the therapeutic benefits of C. butyricum are closely linked to its ability to tolerate continuous antibiotic exposure, providing a scientific rationale for its co-administration with antibiotics.IMPORTANCEClostridium butyricum demonstrates significant therapeutic potential for pediatric antibiotic-associated diarrhea (AAD) by dual modulation of gut microbiota and host physiology. This study reveals its capacity to alleviate intestinal inflammation, restore barrier integrity via upregulation of tight junction proteins and mucins, and rebalance gut microbiota linked to key anti-inflammatory metabolites-even under ongoing antibiotic exposure. These findings position C. butyricum as a targeted probiotic therapy for AAD, offering mechanistic insights to advance microbiome-driven interventions for antibiotic-induced diarrhea in children.

To evaluate the clinical efficacy and health economic value of procalcitonin (PCT)-guided antibiotic discontinuation based on dynamic monitoring in ICU patients with sepsis. A prospective cohort study was conducted involving 180 sepsis patients admitted to our ICU from January 2023 to June 2024. Patients were divided into a PCT-guided group (n=90) and a conventional therapy group (n=90). In the PCT-guided group, antibiotic discontinuation was considered when the daily monitored serum PCT level fell below 0.25 ng/mL and had decreased by ≥80% from its peak, combined with clinical assessment. The conventional group followed standard clinical practice based on experience, imaging, and traditional lab markers. Outcomes including 28-day all-cause mortality, antibiotic duration, ICU and total hospital length of stay (LOS), total medical costs, incidence of antibiotic-associated adverse events, and microbiological resistance profiles were compared. No significant difference was found in 28-day mortality between the PCT-guided and conventional groups (22.2% vs. 25.6%, P&gt;0.05). The PCT-guided group showed significantly shorter antibiotic duration [(8.5±3.2) vs. (12.1±4.5) days], ICU LOS [(10.3±4.1) vs. (13.8±5.2) days], and total hospital LOS [(18.6±6.8) vs. (22.4±7.9) days] (all P&lt;0.01). Total medical costs were significantly lower in the PCT-guided group [(15.3±5.2) vs. (18.9±6.1) ten thousand CNY, P&lt;0.01], primarily due to savings in antibiotic costs and ICU-related expenses. The incidence of antibiotic-associated diarrhea (including C. difficile infection) was significantly lower in the PCT-guided group (5.6% vs. 13.3%, P&lt;0.05).

In Ibero-Latin America, the use of probiotics in pediatrics has increased in recent decades; however, clinical practice shows significant variability across countries and specialties. This situation prompted the development of a regional consensus based on the best available evidence and expert experience. To develop an Ibero-Latin American clinical practice guideline on the use of probiotics in pediatric gastroenterology, hepatology, and nutrition. A multidisciplinary panel of specialists from 12 countries, including gastroenterologists, hepatologists, nutritionists, and pediatricians, was convened. A systematic literature review was conducted in PubMed, Scopus, and Cochrane Library through December 2023. Evidence was assessed using the GRADE methodology, and key clinical questions were formulated. Recommendations were discussed and refined through a three-round Delphi process until consensus was reached. Specific recommendations were developed for the use of probiotics in acute diarrhea, antibiotic-associated diarrhea, gastrointestinal infections, functional gastrointestinal disorders, and inflammatory diseases. Strains and doses with proven efficacy, such as Lactobacillus rhamnosus GG and Saccharomyces boulardii, were identified, and clinical scenarios where probiotic use is not justified were defined. The final consensus incorporated considerations of safety, applicability, and regional context. This guideline represents the first Ibero-Latin American collaborative effort to unify criteria for the use of probiotics in pediatrics, providing a practical and evidence-based framework to improve clinical care across the region.

Probiotics and microbiome-based therapeutics are increasingly used to prevent antibiotic-associated diarrhea (AAD) and support gut microbiota health across children, adults, and elderly populations. Evidence synthesized in this narrative review from randomized controlled trials and meta-analyses (&gt;20,000 participants) suggests that early probiotic administration, particularly Lactobacillus rhamnosus GG, Bifidobacterium species, multistrain formulations, and Saccharomyces boulardii, is associated with a 30–40% relative reduction in AAD incidence across heterogeneous studies, with absolute risk reductions of approximately 5–12% depending on baseline risk, strain, dose, and timing. Probiotics are generally well tolerated, with mild gastrointestinal adverse effects reported in 3–5% of users and rare serious events mainly in immunocompromised individuals. However, heterogeneity in formulations, populations, and limited long-term real-world data underscores the need for further pharmacoepidemiological studies, microbiome surveillance, and evaluation of antimicrobial resistance implications.

BackgroundClostridioides difficile (C. difficile) infection (CDI) is the leading cause of antibiotic-associated diarrhea worldwide. Post-CDI-associated gastrointestinal (GI) dysfunction has been reported in up to 30% of infected patients, suggesting that persistent colonic damage impacts gut function. Recently, we discovered that in the mouse model C. difficile induced post-infection constipation which is proportional to the intensity of intestinal inflammation at the peak of infection. Adenosine A2B receptor activation during CDI generates intense proinflammatory response. Here, we validated the clinical relevance of A2B in CDI by using human colonic biopsies and used a novel highly specific A2B antagonist, ADO5030, in combination with conditional ablation tool in the mouse model to interrogate whether A2B modulation can prevent GI dysfunction post-CDI.MethodsColonic tissues from patients with active CDI and uninfected patients (age and gender matched) were assayed for A2B expression by immunohistochemistry. 2-3-month-old mice (littermates and conditional knockout with specific ablation of A2B in epithelial cells and in whole body cells) were infected with C. difficile, monitored daily and euthanized on day 7 and day 21 post-infection (pi) to assess gut inflammation and GI motility function.ResultsImmunohistochemistry analysis revealed increased A2B expression in both the mucosa-including intestinal epithelial cells- and muscular colonic layers of infected patients compared to uninfected controls. Oral administration of ADO5030 accelerated recovery from CDI-associated clinical symptoms, reduced peak of infection-related gut inflammation, and significantly improved survival in mice. In vivo, A2B blockade effectively prevented CDI-induced delays in GI motility at day 21 pi. Furthermore, global A2B deletion, but not intestinal epithelial-specific A2B ablation, replicated the therapeutic effects of A2B antagonist treatment, suggesting that non-epithelial A2B signaling mediates these benefits.ConclusionOur findings identify A2B as a potential clinically relevant target in patients with CDI. Our preclinical data further show that A2B modulation-independent of epithelial A2B expression, can prevent post-CDI intestinal motility dysfunction.DisclosuresCirle A. Warren, MD, Adovate, LLC: Grant/Research Support|Ferring Pharmaceuticals, Inc.: Site PI for ROAR

The gut microbiome is a complex and dynamic ecosystem that plays a pivotal role in maintaining digestive health, immune function, metabolic regulation, and overall physiological homeostasis. Disruption of this microbial balance, known as dysbiosis, has been implicated in a wide range of gastrointestinal and systemic disorders. Probiotics and fermented foods have emerged as promising dietary strategies for modulating gut microbiota composition and function. This review provides an updated and comprehensive overview of the composition of the gut microbiome and critically examines the mechanisms by which probiotics and fermented foods exert their beneficial effects, including enhancement of intestinal barrier integrity, immunomodulation, competitive inhibition of pathogenic microorganisms, and production of bioactive metabolites. Clinical evidence supporting their use in gastrointestinal conditions such as irritable bowel syndrome, inflammatory bowel disease, antibiotic-associated diarrhea, and functional constipation is discussed, along with safety considerations and regulatory challenges. The review also highlights current research gaps and future perspectives, emphasizing the need for strain-specific validation, long-term clinical studies, and personalized microbiome-based interventions. Overall, probiotics and fermented foods represent valuable, evidence-based components of gut health-oriented nutritional strategies when applied judiciously.

Antibiotic-associated diarrhea (AAD) is known to be a common problem in children receiving antibiotic treatment. However, there is insufficient data in children hospitalized with a diagnosis of pneumonia. The aim of our study was to evaluate the incidence of AAD in children hospitalized with a diagnosis of pneumonia without known comorbidities and to investigate the protective effect of Bifidobacterium animalis ssp. lactis B94 against diarrhea. We conducted a retrospective preliminary observational study in children diagnosed with pneumonia who were admitted to the Department of General Pediatrics at a Tertiary Hospital in the Mediterranean Region of Turkey between January 2021 and December 2023. Children diagnosed with pneumonia who met the study criteria were included in the study. AAD was defined as ≥ 3 loose or watery stools per day for a minimum of 48h during antibiotic treatment. For patients with AAD, clinical data, antibiotic use, diarrhea incidence, and probiotic use were recorded. A total of 202 patients were enrolled. Of these, 116 (57.4%) were female, with a median age of 33.6 months. AAD developed in 14 patients (6.9%). AAD developed more frequently in children younger than 24 months (p = 0.004). Age and gender distribution were similar between the probiotic and control groups (p > 0.05). AAD developed significantly less in the probiotic group (2.9% vs. 11.0%, p = 0.022). After multivariate adjustment, probiotic use remained protective (adjusted OR: 2.435, 95% CI: [(1.464)-(2.717), p = 0.031]). Additionally, children given probiotics required less IV hydration (1.9% vs. 8.0%, p = 0.041). This preliminary observational study suggests the incidence of AAD is low among children hospitalized with pneumonia without comorbid diseases. Prophylactic use of Bifidobacterium animalis ssp. lactis B94 may reduce the risk of diarrhea, though larger prospective studies are needed for confirmation.

Probiotic effects are strain-specific; each strain needs to be assessed individually. In this review, we evaluated the effectiveness of Limosilactobacillus reuteri DSM 17938 in preventing antibiotic-associated diarrhoea (AAD) in children receiving systemic antibiotics. We searched the Cochrane Library, MEDLINE, EMBASE and trial registries (January 2016-July 2025) for randomized controlled trials (RCTs) comparing L. reuteri DSM 17938 with placebo, no treatment, or other probiotics in children. Risk of bias was assessed with Risk of Bias 2 (ROB-2), and certainty of evidence with Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Three RCTs (1070 randomized, 998 analysed) were included. No significant effect was observed with ≤14-day administration (two RCTs, n = 901; risk ratio [RR] 0.85, 95% confidence interval [CI]: 0.26-2.77; low certainty evidence), with interpretation limited by heterogeneity (I2 = 91%) and analytical differences. A regimen of up to 21 days reduced AAD risk (two RCTs, n = 751; RR: 0.50, 95% CI: 0.33-0.75; moderate certainty evidence). A post hoc analysis of trials with follow-up up to 56 days showed no significant effect (three RCTs, n = 998; RR: 0.85, 95% CI: 0.29-2.46; I2 = 83%). A subgroup analysis limited to children receiving amoxicillin-clavulanate showed benefit (two RCTs, n = 690; RR: 0.49, 95% CI: 0.32-0.76; I2 = 0%). L. reuteri DSM 17938 may reduce the risk of AAD in children when administered for up to 21 days or in those receiving amoxicillin-clavulanate. No benefit was found with shorter administration or extended follow-up. Further high-quality trials are needed before routine use can be recommended.

Antibiotic-associated diarrhea (AAD) is a common adverse effect of antibiotic therapy, primarily resulting from gut microbiota disruption. Probiotics have emerged as promising agents to restore intestinal microbial balance and support gastrointestinal health, yet uncertainties remain regarding their mechanisms, strain-specific efficacy, and clinical optimization. This review evaluates the role of probiotics in the prevention and management of AAD, analyzes their clinical efficacy, and explores microbial insights to guide future probiotic interventions. A systematic review of randomized controlled trials, meta-analyses, and microbiome-based studies was performed. Key parameters, including probiotic strain specificity, dosage, treatment duration, and safety, were assessed through data synthesis from clinical and microbiome analyses. Probiotics were found to restore gut microbial diversity, strengthen mucosal barrier function, and modulate immune responses. Evidence supports that Lactobacillus rhamnosus GG and Saccharomyces boulardii effectively reduce the incidence of AAD. Emerging approaches involving personalized probiotic therapy based on individual microbiota profiles demonstrate potential benefits, though heterogeneity in trial design and formulations remains a challenge. Probiotics represent an effective adjunct in AAD prevention and management. Future research should prioritize strain-specific, personalized clinical trials and develop standardized guidelines incorporating microbiome profiling to optimize probiotic selection and therapeutic outcomes.

Suppressive antibiotic therapy (SAT) is used to prevent recurrent prosthetic joint infections (PJI) among patients who undergo debridement, antibiotics, and implant retention (DAIR). We aimed to assess SAT outcomes among younger, immunocompetent patients. Retrospective cohort study. Immunocompetent patients <65 years of age who received DAIR for PJI of the hip, knee, or shoulder. Veterans Affairs hospitals. SAT was divided into short-term (oral antibiotics given for <3 months after guideline concordant therapy) and long-term SAT (>3 months to 5 years of oral antibiotics). The primary outcome was treatment failure (TF) and mortality combined. SAT was a time-dependent covariate in Cox proportional hazards models. Of the 938 patients, 15% received short-term SAT, 20% received long-term SAT, and 65% did not receive SAT. Short- and long-term SAT were significantly associated with decreased hazards of TF or mortality (short-term SAT adjusted hazard ratio (aHR) = 0.27; 95% confidence interval (CI): 0.11, 0.67; Long-term SAT aHR = 0.52; 95% CI: 0.30, 0.89). Short-term SAT was significantly associated with C. difficile infection (aHR: 3.47; 95% CI: 1.38, 8.74). Short-term SAT (aHR: 7.83; 95% CI: 4.80, 12.77) and long-term SAT (aHR: 1.68; 95% CI: 1.19, 2.38) were significantly associated with antibiotic-associated diarrhea. Long-term SAT was not significantly associated with TF alone (aHR = 0.61; 95% CI: 0.32, 1.16). SAT was significantly associated with decreased death or TF and increased side effects. Benefits and risks must be weighed before prescribing SAT to younger, immunocompetent patients.