Probiotics in gastroenteritis in children: A systematic review

Open Access IMC Journal of Medical Science Review Article Probiotics in gastroenteritis in children: A systematic review * Elizabeth A.K. Jones, Amal K. Mitra , Anamika Bisht, Precious Patrick Edet, Faith Iseguede, Ebele Okoye Department of Epidemiology & Biostatistics, Jackson State University, Jackson, MS, USA Abstract Background and objectives: Gastroenteritis is the second leading cause of death among children worldwide. It is a preventable and treatable disease, yet it affects 3 to 5 million children and is the cause of approximately 10% of hospitalizations globally. This systematic review aims to identify the effectiveness of probiotics in treating acute gastroenteritis in children globally and also to provide results of quality research to healthcare-related communities about possible therapies of the condition. Methods: This study follows the PRISMA guidelines for systematic reviews of 29 quantitative studies conducted between 2014-2023. A quality appraisal of the selected studies was conducted using CADIMA and a rating scale of 0 to 3 based on a few predetermined criteria. Results: Sample sizes varied from 29 to 1811, with a median of 200. Globally, there are mixed findings about the roles and benefits of probiotics to treat acute gastroenteritis in children. This is possibly due to the type of probiotic, the type of disease, and treatment adherence. Conclusions: Findings from this systematic review suggest that probiotics play a crucial role in improving children’s health outcomes. Therefore, it is important to promote and implement the use of probiotic therapies in the treatment of acute gastroenteritis conditions in children. IMC J Med Sci. 2023; 17(2):010. DOI: https://doi.org/10.55010/imcjms.17.020 Introduction Acute gastroenteritis is a serious illness prevalent among infants and children globally. Despite being a preventable and treatable disease, acute gastroenteritis remains a major cause of pediatric morbidity and mortality, especially in developing countries. Every year, around 3 to 5 billion children worldwide suffer from acute gastroenteritis resulting in approximately 12% of death in children aged 5 years or younger [1]. In addition, an estimated 10% of hospitalizations in children under 5 years were attributed to acute gastroenteritis globally [2]. Gastroenteritis causes a tremendous economic burden, and the cost of care could weigh heavily on affected families. According to Papadopoulos et al. [3], the five-year economic burden of acute gastroenteritis in Belgium was estimated to be €112 million in direct cost and €927 million (90% of the total costs) in indirect cost, totaling an average cost of €103 per case and €94 per person. Gastroenteritis in children is mostly caused by rotavirus and norovirus [4]. Both pathogens account for about 58% of all acute gastroenteritis cases in the United States [5]. Due to the high rates of acute gastroenteritis and severe outcomes associated with the illness, it is imperative to identify effective treatment therapies to improve health outcomes in children with acute gastroenteritis. Globally, the use of probiotics in treating acute gastroenteritis has been extensively studied by researchers. This has caused controversy and prompted questions about whether or not to use probiotics for treating gastroenteritis. Two clinical trials by Erdoğan et al. [6] and LaMont [7], conducted in Turkey and Europe, respectively, showed better health outcomes from probiotic use in gastroenteritis. Erdoğan et al. [6] reported that *Correspondence: Amal K. Mitra, Department of Epidemiology & Biostatistics, Jackson State University, 350 W. Woodrow Wilson Drive, Room 216 Jackson, MS 39213, USA. E-mail: [email protected] IMC J Med Sci 2023; 17(2): 010 2/11 Saccharomyces boulardii and Bifidobacterium lactis probiotics had an efficacious effect in treating gastroenteritis in children. Furthermore, Lamont [7] tested the effectiveness of probiotics in the treatment of acute gastroenteritis in children and revealed beneficial effects in the hosts or patients. Results from these clinical trials [6,7] suggest the use of probiotics as an important aspect of gastroenteritis research in treating severe outcomes associated with the condition. These outcomes include death, severe dehydration, etc. In contrast, Hojsak [8], a Croatian researcher, argued that “not all probiotic strains have the same efficacy for all clinical indications, therefore, only strains with proven efficacy and safety should be recommended”. This contradictory finding indicates a need for further investigation into the issue of probiotic use in treating gastroenteritis in children. hypothesize that probiotics are able to treat acute gastroenteritis in children. Gastroenteritis among children is the secondleading cause of death worldwide [5]. Due to the poor outcomes associated with gastroenteritis in children, it is crucial to review the effectiveness of probiotics in treating acute gastroenteritis in children. It is also vital to identify new or effective therapies to improve the health outcomes of children afflicted with gastroenteritis. Furthermore, improving children's health, safety, and well-being, a goal that aligns with Healthy People 2030 in the United States, can be achieved by providing adequate medications for children afflicted by diseases such as acute gastroenteritis [9,10]. We Search Guidelines The aim of the systematic review was to assess the effectiveness of probiotics in treating acute gastroenteritis conditions in children and to provide quality research data to healthcare-related communities about use of probiotics as a possible treatment option in childhood gastroenteritis. Materials and methods The systematic review included studies following the PRISMA guidelines [11]. The study focused on published primary articles associated with the impact of probiotics on acute gastroenteritis outcomes in children. Table-1 shows the inclusions and exclusions of the review. The primary search engines used to identify articles included in EBSCOhost, MEDLINE, APA PsychoInfo, APA Psych, Socindex, Google Scholar, and CINAHL. The studies were chosen for the review based on inclusion criteria, such as (1) articles being written in English; (2) being quantitative studies; (3) being scholarly papers; (4) using human participants between the ages of 0-17 years; (5) being associated with acute gastroenteritis; and (6) being associated with probiotics. The search was performed on 25 January 2023. The time limit for the studies was from 2008–2023. Table-2 shows the search string. Table-1: Inclusion and exclusion criteria. Inclusion criteria Quantitative studies Human studies Scholarly papers Age group: 0-17 years Acute gastroenteritis illness Research associated with Probiotics Exclusion criteria Studies that were not in English Studies that only involved ages 18 and older Review articles Not human studies Table-2: Research thread for all databases Search strategies Search terms used: ‘clinical trials’ OR ‘gastroenteritis’ OR ‘probiotics’ OR ‘children Total number of studies excluded based on eligibility criteria Total number of studies excluded due to being duplicates Total number of studies excluded because they were review articles Total number of studies accepted and reviewed No. of studies available 22,403 22,299 3 72 29 IMC J Med Sci 2023; 17(2): 010 3/11 Screening guidelines The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (2009) were used as a guide to record the review process [11]. Selected abstracts were reviewed to ensure eligibility. Full-text articles of eligible abstracts were retrieved and assessed on whether they answered the research questions and fulfilled the inclusion criteria. Studies were included if a consensus was reached by the researchers. Records identified through database searching (n = 22,403) Additional records identified through other sources (n = 0) Records after duplicates removed (n = 3) Eligibility Records screened (n = 22,400) Full-text articles assessed for eligibility (n = 101) Included Screening Identification Research Information System (RIS) formatted references were exported from the databases, where studies were automatically screened based on the inclusion criteria and then imported into CADIMA. Total studies imported into CADIMA were accessed based on title and abstracts. The researchers assessed the studies twice before discussing if the studies should be chosen for fulltext review. Conflicts were managed by group discussions between the researchers of the study. After the initial discussion, the researchers agreed that 104 studies should be selected for further screening using the inclusion criteria. During this second phase of screening for excluding review articles, the researchers independently screened the 104 articles twice for the second time. Conflicts were managed by group discussions. After Studies included in qualitative synthesis (n = 29) Records excluded (n = 22,299) Full-text articles excluded, with reasons: (n = 72) were review articles Figure-1: PRISMA flow chart showing inclusion and exclusion of studies [11] IMC J Med Sci 2023; 17(2): 010 discussion, 72 more articles were excluded because they were review articles, and 3 more articles were excluded because the articles were duplicated between the primary search engines and finally 29 articles were selected to be included in the systematic review. The PRISMA flow chart (Figure1) depicts the search and inclusion process for the systematic review. 4/11 The total sample size used in studies ranged from 29 to 1811, having a median sample size of 200 (Quartile-1 = 92 and Quartile-3 = 816); 3 out of 29 (10.3%) had sample sizes of more than 1000. In terms of standardized tools, all studies (100%) used standardized assessment tools. An average score of 3 out of 3, meant excellent in 3 studies (10.3%), 2 meant moderate/good in 25 studies (86.2%), and 01 meant poor in one study (3.4%). Quality Appraisal Studies were appraised for quality using CADIMA. Through CADIMA, standards for critical appraisal and the rating scale were defined. We followed the critical appraisal tools for systematic reviews developed by the University of Adelaide, South Australia [12]. A rating scale from 0 to 3 was based on the following criteria: (1) Study design— cross-sectional, case–control, or cohort study = 1, otherwise = 0; (2) Sample size—large = 1, small = 0; (3) Selection of participants—random selection or lack of bias = 1, non-random sample or convenience sample or presence of bias = 0 points. Based on the above-mentioned criteria, the researchers rated each of the 29 studies independently from a range of 0 to 3. Due to having no major inter-observer variations in the evaluation of the quality of the studies, an average of the three scores was presented in Table-3 under the quality appraisal section. Results A summary of the methodology, characteristics of findings, the impact of probiotics on acute gastroenteritis outcomes in children, quality appraisal, and the countries of the studies are presented in Table-3. Of the 29 studies reviewed, 5 were conducted in the United States, and Iran, 3 were conducted in Europe, 2 were conducted in Canada, India and Poland, and 1 each in Belgium, Romania, Turkey, Bangladesh, China, Uganda, Botswana, Mexico, Korea, and Canada/United States. All 29 studies were clinical trials [13-41]. All of the selected studies were conducted among children, ranging from infancy to adolescents/ teenagers. Benefits of probiotics in the treatment of acute gastroenteritis in children Of the 29 studies, 19 (65.5%) showed the benefits of probiotics in gastroenteritis treatment. Five studies supported the notion that probiotics improved acute gastroenteritis conditions in children [13-15, 26, 30]. Nocerino et al. found that probiotics lowered acute gastroenteritis in children [13]. Hesaraki et al. concluded that probiotics improved acute gastroenteritis conditions by improving recovery, reducing disease severity, and improving vital signs [14]. Lopetuso et al. have found probiotics to be effective in treating acute gastroenteritis [15]. Schnadower et al. showed the benefits of adherence to probiotic treatments when treating acute gastroenteritis in children, which resulted in better outcomes [26]. Mosaddek et al. also found improved outcomes for children with acute gastroenteritis after being prescribed probiotics [30]. Two studies by Schnadower et al. and Mosaddek et al. revealed that the use of probiotics in the treatment of gastroenteritis in children resulted in better outcomes in ambulatory settings and quicker recovery times [27, 30]. Eight studies also determined that probiotics reduced acute gastroenteritis in children [18, 25,28-29, 32, 35, 37, 40]. Three studies have shown that the use of probiotics reduced hospitalization rates for children with acute gastroenteritis [29, 32, 33, 38]. One study reported that probiotics significantly reduced the duration of rotaviral diarrhoea [20]. Two studies also concluded that probiotics improved outcomes for children diagnosed with special conditions associated with acute gastroenteritis, such as nosocomial infections [39] and hyperbilirubinemia [36]. IMC J Med Sci 2023; 17(2): 010 5/11 Lack of benefits of probiotics in the treatment of acute gastroenteritis in children Of the 29 studies, 8 (27.6%) failed to validate the benefits of probiotics in gastroenteritis in children. Those studies found no benefit or improvement in treating acute gastroenteritis in children with probiotics [17,19,21-24,31,41,]. One study by Ahmadipour et al. [31] even emphasized that zinc supplementation was more effective than probiotics in treating acute diarrhea. Another study by Freedman et al. [22] revealed that probiotics had no effect on immunoglobulin A modulation, which is the antibody that helps the body to fight infections. A study by Olek et al. [41] determined that probiotics had no impact on improving acute gastroenteritis symptoms, including diarrhea frequency or abdominal symptoms. Mixed results in treatment of acute gastroenteritis in children Of the 29 studies, 2 (6.9%) reported mixed results. One study by Szymanski and Szajewska [16] found that probiotics reduced hospitalizations from acute gastroenteritis but not the diarrheal symptoms. Another study by Bhat et al. [38] observed that probiotics reduced diarrheal output in patients receiving outpatient treatment for gastroenteritis but not in hospitalized patients. Table-3: Impact of Probiotics on Acute Gastroenteritis Outcomes in Children Author [Ref] Major Findings Treatment Impact of Probiotics on Acute GE in Children Quality Appraisal (Out of 3) Country of Study Nocerino et al. [13] n = 377; The proportion of children with acute gastroenteritis was lower in group A (13%) for children given daily cow’s milk and for group B (19.5%), who were given a probiotic (Lactobacillus paracasei) Positive 2-good Europe Hesaraki et al. [14] n = 84; Probiotic (kidilact) improved recovery, reduced disease severity, and improved vital signs in children with acute gastroenteritis Positive 2-good Iran Lopetuso et al. [15] n = 1811; Gelatin tannate and tyndallized probiotics were highly effective in the treatment of acute gastroenteritis Positive 3-excellent Europe Szymanski and Szajewska [16] n = 91; Probiotic (L. reuteri) did not reduce the duration of diarrhea, but it did reduce hospitalizations associated with acute gastroenteritis Positive/ No 2-good Poland Freedman et al. [17] n = 1565; In Canada and the U.S., probiotics did not benefit children with acute gastroenteritis No Refeey et al. [18] n = 160; Probiotic (L. acidophilus) reduced the severity of acute diarrhea associated with acute gastroenteritis in children Positive 3-excellent Canada & United States 2-good Iran IMC J Med Sci 2023; 17(2): 010 6/11 Freedman et al. [19] n = 886; Probiotics (Lactobacilli) did not prevent the development of moderate to severe acute gastroenteritis within the 14 days of the study’s enrollment No 2-good Canada Lee et al. [20] n = 29; Probiotic (L. acidophilus) was an effective treatment for acute rotaviral gastroenteritis Positive 2-good Korea Freedman et al. [21] n = 816; No evidence supported the benefits of routine probiotic administration to children with acute gastroenteritis regardless of infecting virus No 2-good United States Freedman et al. [22] n = 133; Probiotic had no effect on immunoglobulin A modulation in children with acute gastroenteritis No 2-good Canada Schnadower et al. [23] n = 813; Probiotic L. rhamnosis GG (LGG) did not improve outcomes in children with acute gastroenteritis No 2-good United States Schnadower et al. [24] n = 971; a 5-day course of L. rhamnosis GG did not lead to better outcomes among preschool children with acute gastroenteritis No 2-good United States Kluijfhout et al. [25] n = 46; Use of probiotics normalized stool consistency significantly or improved diarrhearelated acute gastroenteritis symptoms Positive 2-good Belgium Schnadower et al. [26] n = 971; Adherence to probiotic treatment for acute gastroenteritis resulted in better outcomes Positive 2-good United States Schnadower et al. [27] n = 970; there were benefits associated with probiotic (LGG) administration in ambulatory children presented to the emergency department with acute gastroenteritis Positive 2-good United States Condratovici et al. [28] n = 36; The use of xyloglucan (probiotic) resulted in faster onset of action and improvement of diarrheal symptoms associated with acute gastroenteritis Positive 2-good Romania Dinleyici et al. [29] n = 1200; Probiotics led to reduced rates of hospitalization and reduced diarrhea for children with acute gastroenteritis Positive 3-excellent Turkey Mosaddek et al. [30] n = 166; The use of probiotics resulted in quicker recovery from acute gastroenteritis (due to rotavirus, E. coli, multiorganisms, Campylobacter, Vibrio cholerae, Salmonella, Shigella, and Klebsiella Positive 1-poor Bangladesh IMC J Med Sci 2023; 17(2): 010 7/11 Ahmadipour et al. [31] n = 146; Zinc was more effective than probiotics in treating viral diarrhea associated with acute gastroenteritis in children No 2-good Iran Sudha et al. [32] n = 200; Probiotic (B. clausii) reduced diarrhea associated with acute gastroenteritis in children Positive 2-good India Chen et al. [33] n = 194; 3 probiotic strains (Bifidobacterium lactis Bi07, Lactobacillus rhamnosus HN001, and Lactobacillus acidophilus NCFM) resulted in shorter durations of diarrhea, hospitalizations, and improved health outcomes among children with acute gastroenteritis Positive 2-good China Grenov et al. [34] n = 400; Probiotics had no effect on diarrhea in children with acute gastroenteritis conditions that were associated with severe acute malnourishment duringhospitalization, but probiotics did reduce the number of days with diarrhea in children receiving outpatient treatment Positive/No 2-good Uganda GutierrezCastrellon et al. [35] n = 336; Probiotic reduced the frequency and duration of episodic diarrhea in children with acute gastroenteritis conditions Positive 2-good Mexico Torkamen et al. [36] n = 92; Probiotics were beneficial in the treatment of infants with hyperbilirubinemia associated with acute gastroenteritis Positive 2-good Iran Sharif et al. [37] n=200; Probiotics resulted in significantly lower days of diarrhea among children with acute gastroenteritis outcomes Positive 2-good Iran Bhat et al. [38] n = 120; The probiotic was effective in the reduction of diarrhea and hospitalizations in children with acute gastroenteritis Positive 2-good India Bruzzese et al. [39] n = 90; Probiotic (Lactobacillus GG) reduced the incidence of nosocomial infections associated with acute gastroenteritis in children Positive 2-good Europe Pernica et al. [40] n = 76; Probiotic resulted in lower odds of diarrhea from acute gastroenteritis conditions Positive 2-good Botswana Olek et al. [41] n = 438; Probiotic (Lactobacillus plantarum) did not reduce the incidence of diarrhea, the frequency of diarrhea, or the incidence of abdominal symptoms associated with acute gastroenteritis in children No 2-good Poland Note: GE = Gastroenteritis IMC J Med Sci 2023; 17(2): 010 Discussion Gastrointestinal benefits of probiotics In this systematic review, there was strong evidence to support probiotics' potential to improve acute gastroenteritis in children. Probiotics have been shown to improve acute gastroenteritis outcomes in children by reducing the severity of the conditions and improving recovery times [14,18,30]. Probiotics have also been shown to significantly reduce diarrheal symptoms associated with acute gastroenteritis [25,28,29,32]. Probiotics as an effective therapy for acute gastroenteritis illnesses in children lead to improved outcomes. This includes reductions in severe dehydration and death. This finding has been supported by two other studies, Hania et al. [42] and Guarino et al. [43]. These authors found significant relationships between probiotic use and improved outcomes for acute gastrointestinal symptoms in children. Hospitalizations and the use of probiotic therapies The duration and frequency of hospitalizations for children using probiotics as a treatment for gastroenteritis were further evaluated in this review. Findings have revealed that the use of probiotics as a treatment therapy for children with acute gastroenteritis conditions has also resulted in reduced hospitalization rates [16,29, 33]. The reduction of hospitalizations in children with acute gastroenteritis illnesses not only benefits the health of the affected children but also supports their emotional well-being. Children who are hospitalized have higher rates of psychological distress, resulting in trauma or stress [44]. This is a further example of how probiotic therapies can be beneficial. According to Dinleyici et al. and Guandalini et al., probiotic treatment for acute gastroenteritis conditions in children reduced hospitalizations, duration, and frequency [45,46]. No substantial benefits associated with the use of probiotics While the majority of the studies in the review revealed the benefits of using probiotics for treating childhood gastroenteritis, there are still some studies that found no benefits of probiotics. 8/11 In this review, 8 studies found no benefits to probiotics for gastroenteric illnesses in children. Three studies found that probiotics did not reduce gastroenteritis severity, or yield better outcomes [17,19,24]. Two studies found no clinical benefit, relief in clinical symptoms, or viral clearance when using probiotics to treat gastroenteritis conditions [21,23]. Two studies also found no reduction in the incidence of watery stool, the mean number of loose stools, or abdominal symptoms [22,41]. Finally, one study compared the use of probiotics to zinc supplementation for the treatment of gastroenteritis conditions. The study found that zinc supplementation improved outcomes in terms of reducing hospitalization or duration and causing fewer complications [31]. These findings could have differed from the majority of studies due to the type of probiotics used, the type of gastroenteritis condition being treated, the treatment course, and adherence to treatment by patients. Conclusions Globally, probiotics have played a significant role in improving acute gastroenteritis in children. Probiotics have improved recovery, reduced severity, reduced diarrheal-related symptoms, and reduced hospitalizations in children with acute gastroenteritis conditions. Revealing that children could benefit from probiotic therapies, it is very important to support the use of probiotic therapies in the treatment of acute gastroenteritis in children. Further research is needed to study the roles of innovative probiotic therapies in treating acute and chronic gastroenteritis of multiple etiologies in children. Author’s contribution AKM conceptualized the study. EAKJ extracted the data. AKM validated the study. EAKJ, AB, PPE, FI, and EO prepared the original draft. EAKJ and AKM reviewed and edited the manuscript. All authors have read and agreed to the published version of the manuscript. Competing interest No competing interest/conflict of interest. IMC J Med Sci 2023; 17(2): 010 Funding No funding sources. References 1. 2. 3. 4. Salami A, Fakih H, Chakkour M, Salloum L, Bahmad HF, Ghssein G. Prevalence, risk factors and seasonal variations of different Enteropathogens in Lebanese hospitalized children with acute gastroenteritis. BMC Pediatr. 2019; 19(1): 137. doi:doi.org/10.1186/s12887-019-1513-8. Oppong TB, Yang H, Amponsem-Boateng C, Kyere EKD, Abdulai T, Duan, G, et al. Enteric pathogens associated with gastroenteritis among children under 5 years in sub-Saharan Africa: a systematic review and meta-analysis. Epidemiol Infect. 2020; 148: e64. doi:doi.org/10.1017/S0950268820000618. Papadopoulos T, Klamer S, Jacquinet S, Catry B, Litzroth A, Mortgat L, et al. The health and economic impact of acute gastroenteritis in Belgium, 2010–2014. Epidemiol Infect. 2019; 147: e146. doi:10.1017/S095026881900044X. Afework, DT, Shumie MK, Endalew GF, Adugna AG, Tarekegn BG. Pooled prevalence and genetic diversity of norovirus in Africa: a systematic review and meta-analysis. Virol J. 2022; 19(115). doi:doi.org/10.1186/s12985-022-01835-w. 9/11 9. U.S. Department of Health and Human Services. Healthy People 2030. Place of Publication: Office of Disease Prevention and Health Promotion. USA. 10. U.S. National Library of Medicine. Probiotics in Children.Place of Publication: NCBI. National Center for Biotechnology Information; USA. 11. Moher D. Liberati A. Tetzlaff J, Altman DG. The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009; 6(7): e1000097. 12. Joanna Briggs Institute. JBI Critical Appraisal Tools. Place of Publication: The University of Adelaide, Adelaide, Australia. 13. Nocerino R, Paparo L, Terrin G, Pezzella V, Amoroso A, CosenzaL, et al. Cow's milk and rice fermented with Lactobacillus paracasei CBA L74 prevent infectious diseases in children: A randomized controlled trial. Clin Nutr (Edinburgh, Scotland). 2017; 36(1): 118125. doi: doi.org/10.1016/j.clnu.2015.12.004. 14. Hesaraki M. Effect of probiotic supplement (kidilact) on prevention of acute diarrhea in children: A double-blind randomized clinical trial. Int J Res Med Sci. 2017; 5(7): 2861-2864. doi: doi.org/10.18203/2320-6012.ijrms20172595. 5. Rivera-Dominguez G, Ward R. Pediatric Gastroenteritis. In: StatPearls [Internet]. 2023. PMID: 29763114. 15. Lopetuso L, Graziani C, Guarino A, Lamborghini A, Masi S, Stanghellini V. Gelatin tannate and tyndallized probiotics: a novel approach for the treatment of diarrhea. Eur Rev Med Pharmacol Sci. 2017; 21(4): 873–883. 6. Erdoğan O,Tanyeri B, Torun E, Gönüllü E, Arslan H, Erenberk U, et al. The comparison of the efficacy of two different probiotics in rotavirus gastroenteritis in children. J Trop Med. 2012; 2012: 787240. doi: doi.org/10.1155/2012/787240. 16. Szymaoski H, Szajewska H. Lack of efficacy of Lactobacillus reuteri DSM 17938 for the treatment of acute gastroenteritis: A randomized controlled trial. Pediatr Infect Dis J. 2019; 38(10): e237–e242. doi: doi.org/10.1097/INF.0000000000002355. 7. LaMont JT. Probiotics for children with gastroenteritis. N Engl J Med. 2018; 379(21): 2076–2077. doi:doi.org/10.1056/nejme1814089 8. Hojsak I. Probiotics in children: what is the evidence? Pediatr Gastroenterol Hepatol Nutr. 2017; 20(3): 139–146. doi:doi.org/10.5223/pghn.2017.20.3.139. 17. Freedman SB, Finkelstein Y, Pang XL, Chui L, Tarr PI, VanBuren JM, et al. Pathogen-specific effects of probiotics in children with acute gastroenteritis seeking emergency care: A randomized trial. Clin Infect Dis. 2022; 75(1)): 55–64. doi: doi.org/10.1093/cid/ciab876. 18. Rafeey M, Ostadrahimi A, Ghorashi Z, Boniadi, M. Lactobacillus acidophilus yogurt and IMC J Med Sci 2023; 17(2): 010 supplement in children with acute diarrhea: A clinical trial. Res J MedSci.2008; 2(1): 13-18. 19. Freedman SB, Williamson-Urquhart S, Farion KJ, Gouin S, Willan AR, Poonai N, Hurley K, et al. Multicenter Trial of a Combination Probiotic for Children with Gastroenteritis. N Eng J Med. 2018; 379(21): 2015-2026. doi: doi.org/10.1056/NEJMoa1802597. 20. Lee DK, Park JE, Kim MJ, Seo JG, Lee JH, Ha NJ. Probiotic bacteria, B. longum and L. acidophilus inhibit infection by rotavirus in vitro and decrease the duration of diarrhea in pediatric patients. Clin Res Hepatol Gastroenterol. 2015; 39(2): 237-244. doi: doi.org/10.1016/j.clinre.2014.09.006/. 21. Freedman SB, Xie J, Nettel-Aguirre A, Pang XL, Chui L, Williamson-Urquhart S, et al. Pediatric Emergency Research Canada Probiotic (PERC) Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) Trial Group. A randomized trial evaluating virus-specific effects of a combination probiotic in children with acute gastroenteritis. Nat Commun. 2020; 11(1): 2533. doi: doi.org/10.1038/s41467-020-16308-3. 22. Freedman SB, Horne R, Johnson-Henry K, Xie J, Williamson-Urquhart S, Chui L, et al. Pediatric Emergency Research Canada Probiotic Regimen for Outpatient Gastroenteritis Utility of Treatment (PROGUT) Trial Group. Probiotic stool secretory immunoglobulin A modulation in children with gastroenteritis: a randomized clinical trial. Am J Clin Nutr. 2021; 113(4): 905– 914. doi:doi.org/10.1093/ajcn/nqaa369. 23. Schnadower D, Sapien RE, Casper TC, Vance C, Tarr PI, O'Connell KJ, et al. Association between age, weight, and dose and clinical response to probiotics in children with acute gastroenteritis. J Nutr. 2021; 151(1): 65–72. doi: doi.org/10.1093/jn/nxaa313. 24. Schnadower D, Tarr, PI, Casper, TC, Gorelick, MH, Dean, JM, O'Connell, KJ, et al. Lactobacillus rhamnosus GG versus placebo for acute gastroenteritis in children. N Engl J Med. 2018; 379(21): 2002–2014. doi: doi.org/10.1056/NEJMoa1802598. 25. Kluijfhout S, Trieu TV, Vandenplas Y. Efficacy of the probiotic probiotical confirmed in acute 10/11 gastroenteritis. Pediatr Gastroenterol, Hepatol Nutr. 2020; 23(5): 464–471. doi: doi.org/10.5223/pghn.2020.23.5.464. 26. Schnadower D, Roskind CG, VanBuren JM, Powell EC, Norris JG, Tarr PI, et al. Factors associated with nonadherence in an emergency department-based multicenter randomized clinical trial of a probiotic in children with acute gastroenteritis. J Pediatr Gastroenterol Nutr. 2021; 72(1): 24-28. doi: doi.org/10.1097/MPG.0000000000002904. 27. Schnadower D, Tarr PI, Casper TC, Gorelick MH, Dean MJ, O'Connell KJ, et al. Randomized controlled trial of Lactobacillus rhamnosus (LGG) versus placebo in children presenting to the emergency department with acute gastroenteritis: the PECARN probiotic study protocol. BMJ open, 2017; 7(9): e018115. doi: doi.org/10.1136/bmjopen-2017-018115. 28. Pleșea Condratovici C, Bacarea V, Piqué N. Xyloglucan for the treatment of acute gastroenteritis in children: results of a randomized controlled clinical trial. Gastroenterol Res Pract. 2016; 2016: 6874207. doi:doi.org/10.1155/2016/6874207. 29. Dinleyici EC. Pre-, probiotics and synbioticsin infectious diarrhea. J Pediatr Gastroenterol Nutr. 2016; 63(1S): S50-S51. doi: 10.1097/01.mpg.0000489624.12936.04. 30. Mosaddek AS, Rizvi M, Akter R, Islam S, Hossain N, Iqbal, H, et al. Effect of probiotics in the treatment of acute watery diarrhoea in children admitted to a tertiary care hospital in Bangladesh: A non-randomized prospective clinical trial. Int J Collab Res Intern Med Public Health. 2022; 14(2): 01-07. 31. Ahmadipour S, Mohsenzadeh A, Alimadadi H, Salehnia M, Fallahi A. Treating viral diarrhea in children by probiotic and zinc supplements. Pediatr Gastroenterol Hepatol Nutr. 2019; 22(2): 162-170. doi: doi.org/10.5223/pghn.2019.22.2.162. 32. Sudha MR, Jayanthi N, Pandey DC, Verma AK. Bacillus clausii UBBC-07 reduces the severity of diarrheain children under 5 years of age: a double-blind placebo-controlled study. Benef Microbes. 2019; 10(2): 149-154. doi: doi.org/10.3920/BM2018.0094. IMC J Med Sci 2023; 17(2): 010 33. Chen K, Xin J, Zhang G, Xie H, Luo L, Yuan S, et al. A combination of three probiotic strains for treatment of acute diarrheain hospitalized children: an open-label, randomized controlled trial. Benef Microbes. 2020; 11(4): 339-346. doi: doi.org/10.3920/BM2020.0046. 34. Grenov B, Namusoke H, Lanyero B, NabukeeraBarungi N, Ritz C, Mølgaard C, et al. Effect of probiotics on diarrhea in children with severe acute malnutrition: A randomized controlled study in Uganda. J Pediatr Gastroenterol Nutr. 2017; 64(3): 396-403. doi:.org/10.1097/MPG.0000000000001515. 35. Gutierrez-Castrellon P, Lopez-Velazquez G, Diaz-Garcia L, Jimenez-Gutierrez C, MancillaRamirez J, Estevez-Jimenez J, et al. Diarrhea in preschool children and Lactobacillus reuteri: a randomized controlled trial. Pediatrics. 2014; 133(4): e904–e909. doi: doi.org/10.1542/peds.2013-0652. 36. Torkaman M, Mottaghizadeh F, Khosravi MH, Najafian B, Amirsalari S, Afsharpaiman S. The effect of probiotics on reducing hospitalization duration in infants with hyperbilirubinemia. Iranian J Pediatr. 2016; 27(1): e5096. doi: doi.org/10.5812/ijp.5096/. 37. Sharif MR, Kashani HH, Ardakani AT, Kheirkhah D, Tabatabaei F,Sharif A. The Effect of a yeast probiotic on acute diarrhea in children. Probiotics Antimicrob Proteins. 2016; 8(4): 211214. doi: doi.org/10.1007/s12602-016-9221-2. 38. Bhat S, Shreekrishna GN, Savio CD. Efficacy of probiotics in acute diarrheain children. Int J Contemp Pediatr. 2018; 5(4): 1646-1650. doi: doi.org/10.18203/2349-3291.ijcp20182582. 39. Bruzzese E, Fedele MC, Bruzzese D, Viscovo S, Giannattasio A, Mandato C, et al. Randomized clinical trial: a Lactobacillus GG and micronutrient-containing mixture is effective in reducing nosocomial infections in children, vs. placebo. Aliment Pharmacol Ther. 2016; 44(6): 568–575. doi: doi.org/10.1111/apt.13740. 40. Pernica JM, Steenhoff AP, Mokomane M, Moorad B, Lechiile K, Smieja M, et al. Rapid enteric testing to permit targeted antimicrobial therapy, with and without Lactobacillus reuteri probiotics, for pediatric acute diarrhoeal 11/11 disease in Botswana: A pilot, randomized, factorial, controlled trial. PloS One. 2017; 12(10): e0185177. doi:doi.org/10.1371/journal.pone.0185177. 41. Olek A, Woynarowski M, Ahrén IL, Kierkuś J, Socha P, Larsson N, et al. Efficacy and safety of Lactobacillus plantarum DSM 9843 (LP299V) in the prevention of antibiotic-associated gastrointestinal symptoms in children randomized, double-blind, placebo-controlled study. J Pediatr. 2017; 186: 82-86. doi:doi.org/10.1016/j.jpeds.2017.03.047/. 42. Hania S, Alfredo G, Iva H, Flavias I, Sanja K, Raanan S, et al. Use of probiotics for management of acute gastroenteritis: A position paper by the ESPGHAN Working Group Probiotics and Prebiotics. J Pediatr Gastroenterol Nutr. 2014; 58(4): 531-539. doi: 10.1097/MPG.0000000000000320. 43. Guarino A, Guandalini S, Lo Vecchio A. Probiotics for prevention and treatment of diarrhea. J Clin Gastroenterol. 2015; 49 Suppl 1: S37-45. doi: 10.1097/MCG.0000000000000349. 44. Li WHC, Chung JOK, Ho KY, Kwok BMC. Play interventions to reduce anxiety and negative emotions in hospitalized children. BMC Pediatr. 2016; 16(36). doi: doi.org/10.1186/s12887-016-0570-5. 45. Dinleyici EC, Dalgic N, Guven S, Ozen M, Kara A, Arica V, et al. The effect of a multispecies synbiotic mixture on the duration of diarrhea and length of hospital stay in children with acute diarrhea in Turkey: single-blinded randomized study. Eur J Pediatr. 2013; 172(4): 459-464. doi: 10.1007/s00431-012-1903-5. 46. Guandalini S. Probiotics for prevention and treatment of diarrhea. J Clin Gastroenterol. 2011; 45 Suppl: S149-153. doi: 10.1097/MCG.0b013e3182257e98. Cite this article as: Jones EAK, Mitra AK, Bisht A, Edet PP, Iseguede F, Okoye E. Probiotics in gastroenteritis in children: A systematic review. IMC J Med Sci. 2023; 17(2):010. DOI: https://doi.org/10.55010/imcjms.17.020