Abstract
Acute diarrhoea in young children is very common and remains an important health problem. This study aimed to assess the effectiveness of a multistrain synbiotic compound in a drops formulation for treating acute diarrhoea of probable viral origin in children aged ≤2 years. A prospective, multicentre, randomised, open-label and controlled study was conducted in a cohort of 75 children (40 received a one-week treatment with a 7-multistrain synbiotic drops plus supportive therapy and 35 received supportive therapy alone). Based on the WHO definition of diarrhoea (≥3 loose/liquid stools/day) and the Bristol Stool Form Scale (BSFS) (stool consistency 5-7), a higher percentage of children in the synbiotic group experienced less diarrhoea (70%) vs controls (88.6%) (
1 Introduction
Diarrhoea defined as loose, watery stools three or more times a day is a very common health problem in children. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) defines acute gastroenteritis (diarrhoea) as a decrease in the consistency of stools (loose or liquid) and/or an increase in the frequency of evacuation (typically ≥3 in 24 h), with or without fever or vomiting. Despite improved hygienic conditions and effective interventions including rotavirus vaccine, young children may experience as many as 1 to 5 episodes of acute diarrhoea each year and according to the Global Burden of Disease Study in 2016, diarrhoea was the fifth leading cause of death among children younger than five years (GBD 2016 Diarrhoeal Disease Collaborators, 2018). Although most of these deaths occur in low and middle-income countries due to inequalities, lack of resources, malnutrition, unsafe water and poor sanitation, diarrhoea remains an important health problem in developed countries as it leads to frequent emergency room visits, admission to the hospital, high burden to society, families and economic costs for the healthcare systems (Elliott, 2017; Guarino et al., 2020; Pinzón-Rondón et al., 2015). However, implementation of an integrated approach of key interventions to effectively prevent and treat childhood diarrhoea still remains an unmet challenge in global child health (Mokomane et al., 2018; World Health Organization/The United Nations Children’s Fund (UNICEF), 2013).
Acute diarrhoea should be treated promptly and effectively to prevent severe dehydration, which can be life-threatening if untreated. Treatment is primarily supportive, particularly in viral gastroenteritis, based on the administration of oral rehydration solution, age-appropriate diet, limiting foods high in fat and simple sugars, etc. (Burkhart, 1999). Pharmacological treatment is not usually recommended in the management of diarrhoea in children (Burkhart, 1999). Imbalance and alterations in the composition of gut microbiota in children with diarrhoea, with significant decreases in Lacticaseibacillus, Lactobacillus, Bifidobacterium, and Enterococcus in the intestine have been the rationale for the use of probiotics, which can improve the intestinal microenvironment, promote immunity and enhance resistance. Systematic reviews and meta-analyses have provided a good body of evidence to support the efficacy and tolerability of probiotics and synbiotics (a mixture of probiotics and prebiotics) in the management of pediatric acute gastroenteritis (AGE) (Applegate et al., 2013; Florez et al., 2018; Li et al., 2021). Probiotic mixtures can include multiple strains of microorganisms, as it has been suggested that multi-species probiotic mixtures might be more beneficial for restoring the microbiome after dysbiosis has occurred. Advantages of multi-strain mixtures may include synergistic effects of different strains (increased adhesion, increased pathogen inhibition) and the combination of different mechanisms of action. Nonetheless, a systematic review concluded that multi-strain probiotics are not always more beneficial than single-strain ones. One mixture was superior for Helicobacter pylori eradication, but a single strain was superior for necrotizing enterocolitis prevention (McFarland, 2021). According to the International Scientific Association for Probiotics and Prebiotics (ISAPP), a synbiotic is defined as a mixture comprising live microorganisms and substrate(s) selectively utilised by host microorganisms that confers a health benefit on the host (Swanson, 2020). The overall benefits of synbiotics reported in clinical trials of acute diarrhoea in children include a rapid normalisation of the gastrointestinal microbiota, a reduction in the duration of diarrhoea, quicker improvement in stool frequency and consistency, lesser administration of additional medications, reduced length of hospitalisation and higher treatment satisfaction (Jog, 2019; Yang et al., 2019).
In clinical practice, the diversity of probiotics/synbiotics makes choosing an appropriate probiotic product challenging. Moreover, the benefits of probiotics should be assessed in well-defined human populations, with adequate scientific methodology, in a specific disease or indication, evaluating specific strains and using the quantities of the product that is marketed (Cucalón Arenal and Blay Cortés, 2020a,b).
Some published studies on the use of synbiotics with different compositions in the treatment of AGE in children have consistently shown faster resolution of diarrhoea, with reduced daily stool outputs, better stool consistency, and less concomitant medication used, when compared with placebo or supportive treatment only (Guarino et al., 2018; Gundogdu, 2013; Nocerino and Canani, 2012; Vandenplas and De Hert, 2011). Moreover, treatment with synbiotic is cost effective due to the reduction in add-on medical and extra consultations (Vandenplas and De Hert, 2012).
Previous randomised controlled trials with a multistrain synbiotic product based on the combination of seven probiotic species (L. casei, L. rhamnosus, Streptococcus thermophilus, B. breve, L. acidophilus, B. infantis, B. bulgaricus) and fructooligosaccharides as prebiotic (Prodefen®) showed a reduction in the duration of diarrhoea and number of watery stools (Allahverdi et al., 2010; Garcı́a-Menor et al., 2016). One of these studies was conducted in hospitalised Iranian children aged between 1 and 5 years (Allahverdi et al., 2010) and the other in children between 6 months and 12 years of age in the outpatient setting in Spain (Garcı́a-Menor et al., 2016). The use of this synbiotic product increased the proportion of patients without diarrhoea at all time points as compared with controls and reduced the duration of diarrhoea by two days in the subset of children aged 6 months to 2 years (Garcı́a-Menor et al., 2016). Following this line of research, the present randomised controlled trial, PRODINFANT study, was designed to assess the effectiveness of this multistrain synbiotic compound (with updated probiotic strains while maintaining its composition) in a new drops formulation for treating AGE of viral origin in a specific age group of children in the first two years of life. Maintaining the composition refers specifically to the preservation of the probiotic species and the prebiotic component (fructooligosaccharides), consistent with those used in the Garcı́a-Menor et al. (2016) study. The term updated probiotic strains denotes the inclusion of Lacticaseibacillus rhamnosus GG and modifications to the remaining strains.
One of the strains included in this new formulation, Lacticaseibacillus rhamnosus GG, is recommended as an active treatment adjunct to rehydration therapy according to 2020 update guidelines for the management of AGE in children of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases (ES-PGHAN/ESPID) (Szajewska et al., 2020). On the other hand, the strain Streptococcus thermophilus St-21 that is also part of this drops formulation has been investigated as a treatment for irritable bowel syndrome (IBS) in adults. In a multi-centre, randomised, double-blind, placebo-controlled trial involving 202 IBS patients, treatment with a symbiotic containing this strain resulted in stool normalisation 78.1% of IBS patients with diarrhoea and 96.2% of IBS patients with constipation after 12 weeks of treatment with this S. thermophilus St-21-containing synbiotic (Sommermeyer et al., 2024). Finally, in a study that evaluated the impact of an enteral probiotics supplementation protocol including Bifidobacterium infantis HA-116 on the incidence of necrotizing enterocolitis (NEC) in preterm infants, the introduction of this five-strain probiotic coincided with a significant 67% reduction in the incidence of definite NEC. The mechanisms through which these probiotic strains, including Bifidobacterium infantis HA-116, confer benefits may involve enhancing mucosal barrier integrity, competitive exclusion of pathogens, modifying host responses to microbial products, augmenting IgA mucosal responses, improving enteral nutrition, and up-regulating immune responses (Brown et al., 2022).
2 Material and methods
Design and participants
This was a multicentre, prospective, randomised, open-label and controlled clinical trial (PRODINFANT study; ISRCTN Registry identification number: ISRCTN10495554) carried out between September 2020 and November 2021 at 10 paediatric primary care consultations or emergency services throughout Spain. The primary objective of the study was to assess the additional benefit provided by a multi-strain synbiotic formulation as compared with diet and/or oral rehydration (standard treatment) in the resolution of diarrhoea in children with AGE of viral origin aged ≤2 years. Secondary objectives included the effect of the synbiotic compound on the incidence and/or duration of other associated symptoms, and tolerability, safety and acceptability of the product.
Eligible patients were children aged two years or younger who visited the paediatrician in the outpatient setting (primary or the emergency healthcare centre), presenting an acute diarrhoea episode lasting less than 48 h, with a probable viral origin, and in whom diet and/or oral rehydration were considered the most appropriate treatment. A probable viral origin was established because the patient’s history and the presenting symptoms were not correlated with clinical manifestations of gastroenteritis caused by bacterial infection or other type of gastroenteritis. Diarrhoea was defined according to criteria of the World Health Organization (WHO) as the passage of three or more loose or liquid stools per day (or more frequent passage than normal for the individual) (World Health Organization, 2023). Types 5 to 7 of the Bristol Stool Form Scale (BSFS) were used for the definition of loose or liquid (watery) stools (Lewis and Heaton, 1997). Exclusion criteria were as follows: presence of any disease that may cause diarrhoea, different from an infection such as inflammatory bowel disease, food allergy, lactose intolerance, etc., immunodeficiency or other chronic underlying diseases; severe dehydration or malnutrition; visible blood in stools; current pharmacological treatment for diarrhoea; use of antibiotics and/or probiotics within the previous seven days; milk protein allergy; and current participation in another study.
The study was conducted in accordance with the Declaration of Helsinki and approved by the Clinical Research Ethics Committee (CEIC) of Hospital Universitario Puerta de Hierro (Majadahonda, Madrid, Spain). Written informed consent was obtained from the parents or legal tutors of children participating in the study.
Intervention
Children who met the inclusion criteria were assigned a consecutive number at each study site according to the order of arrival, and then randomised to treatment with the synbiotic product (synbiotic group; odd number) or standard supportive measures (control group; even number). All participants regardless of their assigned group received supportive standard treatment with diet and/or oral rehydration therapy. Children randomised to the synbiotic group were administered daily recommended dosage (10 drops) of the synbiotic product (Prodefen® drops, ITALFARMACO, S.A., Alcobendas, Madrid, Spain), with or without food and preferably in the morning for seven consecutive days. The synbiotic product is composed of 1 × 109 colony-forming units (CFU) per daily dose (10 drops) of the following seven probiotic strains: Lacticaseibacillus rhamnosus GG (formerly Lactobacillus rhamnosus GG), Lacticaseibacillus casei HA-108 (formerly Lactobacillus casei HA-108), Lactobacillus acidophilus La-14, Lactobacillus bulgaricus Lb-87, Streptococcus thermophilus St-21, Bifidobacterium breve BB077 and Bifidobacterium infantis HA-116 in combination with 3 mg of fructooligosaccharides (prebiotic). Children assigned to the control group did not receive any other active treatment besides diet recommendations and/or oral rehydration therapy (standard supportive measures).
Study procedures
The study included a 7-day treatment period with 3 visits (1 in-person visit and 2 visits by phone) and a final safety follow-up phone call at day 10. Children visited the study centre (visit 1) where the inclusion criteria were confirmed, the signed informed consent was obtained, and they were assigned to the treatment group. The first dose of the synbiotic product was administered by the investigator at the study centre (day 1) and parents were provided with a drop bottle of the product for treatment during the subsequent six days. Parents of all participants were given a patient diary card in which all information of the study variables had to be recorded on a daily basis. The parents were contacted by phone on days 4 and 7, so that the investigator could collect information on the study variables related to the course of the disease. Data of acceptability and tolerability of treatment were collected on day 7. In addition, on day 10, 3 days after the end of the treatment, adverse events occurring during that period were recorded. If scheduled phones calls were foreseen during the weekend, a 2-day window period was allowed.
Study variables
Efficacy variables assessed from day one to the end of the study included the percentage of children who suffered diarrhoea according to several definitions, the WHO criteria, the Bristol Stool Form Scale (BSFS) criteria, both WHO and BSFS criteria, and the parents’ opinion regarding more stools per day or more fluid in consistency for at least 1, ≥2 or ≥3 consecutive days; number of days of diarrhoea (three or more passage of stools per day) and duration (days) of diarrhoea until the end of the study; percentage of children recovered from diarrhoea (two consecutive days without diarrhoea); characteristics of stool (frequency, consistency according to the BSFS, severity of diarrhoea); and associated symptoms (vomiting, nausea, fever, mucus in stools and abdominal pain), mean duration of symptoms and need for treatment. Other variables included number of visits to the primary care paediatrician or the emergency service as well as the need for concomitant medication. The administration of other probiotics including probiotic rich serum as a complement to the standard supportive measures (diet/oral rehydration) during the participation in the study was not allowed.
The BSFS classifies stool consistency into seven types as follows: type 1, separate hard lumps, like nuts difficult to pass; type 2, sausage-shaped but lumpy; type 3, like a sausage but with cracks on its surface; type 4, smooth and soft (average stool); type 5, soft blobs with clear cut edges; type 6, fluffy pieces with ragged edges, a mushy stool; and type 7, watery, no solid pieces entirely liquid (Lewis and Heaton, 1997). Types 1 and 2 indicate constipation, types 3 and 4 being ideal stools and types 5 to 7 indicating diarrhoea.
Tolerability of the synbiotic product and satisfaction with treatment (acceptability) were evaluated using a 5-point Likert scale, from ‘very good’ to ‘very bad’ and from ‘very satisfied’ to ‘not at all satisfied’, respectively. The impact of treatment on the quality of life and daily activities of the parents was assessed using a 5-point Likert scale (‘not at all affected’, ‘slightly affected’, ‘moderately affected’, ‘very affected’, ‘extremely affected’). Parents of children in the synbiotic group were asked whether they would administer the synbiotic product again in case their child had a similar episode of diarrhoea in the future. The level of adherence to diet/oral rehydration alone (control group) or combined with the study product (synbiotic group) was categorised as poor (<60%), moderate (≥60% to <80%), good (≥80% to <90%) and very good (≥90%). Safety variables included type, frequency and duration of adverse events (AEs).
Study endpoints
Study endpoints were the evolution of diarrhoea according to the WHO definition (≥3 loose or liquid stools/daily), parents’ criteria as more stools/day of a more fluid consistency than usual, and according to BSFS (types 5 to 7) during at least 1, 2, or 3 days; number of days with diarrhoea (≥3 stools for at least 1 day); rate of diarrhoea recovery; improvement in the characteristics of stools (frequency, consistency according to the BSFS, and severity of diarrhoea); disappearance of associated symptoms; the need for medical/treatment intervention (visits to pediatrician/emergency service) and the tolerability and acceptability of treatment.
Statistical analysis
The sample size was calculated based on data of a clinical trial reported by Francavilla et al. (2012) in which the mean duration of diarrhoea was 2.1 days in the synbiotic group and 3.3 in the placebo group. In order to detect a difference of 1.2 (0.4) days in the duration of diarrhoea between the synbiotic and the control groups, a sample of 37 children per treatment group would be required for a statistical power of 76% and a significance level of 5%, which was increased up to 40 children per group (total 80) with an estimation of 8% of children lost to follow-up.
Efficacy endpoints were analysed in the population dataset as treated i.e. children who received at least one day of the treatment prescribed and in whom some follow-up data were provided. The safety population included all randomised children who had received at least one day of the treatment prescribed.
Categorical variables are expressed as frequencies and percentages, and continuous variables as mean and SD or median and interquartile range (IQR) (25th-75th percentile). Differences in the distribution of variables in the two study groups were analysed according to normally or non-normally distribution of data sets, using the chi-square test or the Fisher’s exact test for categorical data, and Student’s t test (parametric test) or the Mann-Whitney U test (non-parametric test) for quantitative data. All analyses were two-tailed and statistical significance was set at
3 Results
Baseline characteristics of children
The study population included 75 children, 40 assigned to the synbiotic group and 35 to the control group. There were 47 (62.7%) males and 28 (37.3%) females, with a mean age of 14.5 (8.1) months. As shown in Table 1, there were no significant differences between the study groups in baseline data recorded at visit 1. Only 4 patients had received previous treatments in the last 7 days, especially analgesics and vitamins. The mean time elapsed from the first loose or liquid stool to visit 1 was 1.0 (0.6) days. Associated symptoms and the characteristics of stools were also similar, except for vomiting, which was more frequent in the control group (34.3% vs 10%,
Baseline characteristics of 75 children included in the study
Citation: Beneficial Microbes 2026; 10.1163/18762891-bja00104
Results of diarrhoea-related variables
Citation: Beneficial Microbes 2026; 10.1163/18762891-bja00104
Diarrhoea
A significantly lower percentage of children assigned to the synbiotic group suffered from diarrhoea for ≥3 consecutive days (based on WHO definition of ≥3 loose/liquid stools/day) as compared with the control group (80% vs 100%.
The median (IQR) days with diarrhoea defined as ≥3 bowel movements/day, was 4 (3-6.5) in the synbiotic group and 6 (5-7) in the control group (
The total duration of the diarrhoea episode was shorter in the synbiotic group (median 3 days, IQR 2-5) than in the control group (median 5, IQR 4-7) (
The mean number of bowel movement throughout the study showed differences in favour of the active treatment since day two until the end of treatment, with differences being statistically significant since day three of therapy (Figure 1). The higher percentage of infants without diarrhoea in the synbiotic group was already noticed on day two (Figure 2).
Mean number of bowel movements during the 7-day study period with significant differences from day 3 to the end of the study in favour of the active treatment group (*
Citation: Beneficial Microbes 2026; 10.1163/18762891-bja00104
Stool consistency
In relation to stool consistency according to BSFS type, there were significant differences between the study groups, with higher stool consistency in the active treatment group as compared with the control group on days 4 and 6 (Figure 3). On day 4, the mean values in the synbiotic group were 5.4 (1.0) and 5.7 (0.9) in the control group (
Associated symptoms, need for medical intervention and treatment
In relation to the duration of associated symptoms, visits to the pediatrician or emergency services or need for concomitant treatment, significant differences between the synbiotic and control groups were not found (Table 3), although for every single parameter the synbiotic group scored better.
Tolerability, acceptability and adherence
Tolerability and acceptability of diarrhoea treatment were higher in the synbiotic treatment group (Table 4). The percentage of the children’s parents who reported a tolerability of the study treatment as ‘very good’ or ‘good’ was significantly higher in the synbiotic group than in the control group (95% vs 69.7%). Also, the percentages of ‘very satisfied’ and ‘quite satisfied’ with the treatment were significantly higher among parents of children assigned to the active treatment (70% vs 39.4%). Ninety-five percent of parents reported the intention of using the synbiotic product in future similar diarrhoea episodes. The impact of the children’s diarrhoea on the quality of life of their parents was similar, but the percentages of ‘not at all affected’ were higher in the synbiotic treatment group.
In relation to compliance with treatment statistically significant differences were not observed. Overall, 57.3% of patients reported a very good level of compliance (≥90%) and 29.3% a poor level of compliance (<60%) regarding supportive treatment (diet and/or rehydration). In the synbiotic group, 100% adherence to the synbiotic product was recorded. The percentage of patients who followed dietary instructions from day 4 to day 6 was significantly higher in the control group (85.3%) than in the synbiotic group (62.5%) (
In all 75 children, 46 (32.0%) adverse events (AEs) were reported, 26 AEs in 12 of the 35 children (34.3%) from the control group and in 20 AEs in 12 of the 40 children (30.0%) from the synbiotic group (
Percentage of infants without diarrhoea (≥3 stools/day) for at least one day over the study period.
Citation: Beneficial Microbes 2026; 10.1163/18762891-bja00104
Changes in stool consistency according to the Bristol Stool Form Scale during the treatment period with significant differences on days 4 (
Citation: Beneficial Microbes 2026; 10.1163/18762891-bja00104
4 Discussion
This open-label randomised controlled study carried out in children of two years of age or younger presenting diarrhoea of probable viral origin showed that a combined treatment of a multistrain synbiotic product (Prodefen® drops) with diet recommendations and/or oral rehydration was more effective to improve the evolution of diarrhoea than standard supportive measures alone. Additional benefits of the use of the synbiotic product as compared with supportive measures included experiencing less diarrhoea with improvement in stool consistency, shortening diarrhoea by two days and decreasing the total duration of the diarrhoeal episode. The rapid effect of the synbiotic product, which was already observed from the second day of treatment and the reduction in the duration of the episode of diarrhoea by two days are relevant findings of the study from a clinical point of view. Furthermore, the use of the synbiotic product showed a very favourable safety and tolerability profile as well as a high level of acceptability by the children’s parents/tutors.
Duration of associated symptoms in the study groups and need for medical intervention and concomitant treatment
Citation: Beneficial Microbes 2026; 10.1163/18762891-bja00104
Tolerability, acceptability/satisfaction with treatment and level of adherence
Citation: Beneficial Microbes 2026; 10.1163/18762891-bja00104
Diarrhoea remains a leading cause of morbidity and mortality among children under five years of age, responsible for killing around 525,000 children every year (World Health Organization, 2023). Moreover, diarrhoea is a leading factor causing malnutrition in children younger than five years. Because of the relevance of this preventable disease, interventions to improve sanitation, personal and food hygiene and education are essential measures in the prophylaxis of diarrhoea. Acute diarrhoea can be caused by different pathogens, particularly enteric pathogens such as Rotavirus, Adenovirus, enterotoxigenic Escherichia coli, Salmonella and Giardia (Florez et al., 2020). Rotavirus is the most common aetiology and laboratory tests are not routinely required because they usually do not affect the management of the disease. Assessment of the hydration status is a key element in the approach of a child with diarrhoea, with oral rehydration therapy and diet recommendations as mainstay of treatment for paediatric diarrhoeal episodes. In a systematic review of diarrhoea duration and severity in children, it was estimated that among children under five years of age, 65% of diarrhoeal episodes were mild with a weighted mean duration of 4.3 days (95% confidence interval [CI] 4.3-4.4), whereas severe episodes showed a weighted mean duration of 8.4 days (95% CI 8.1-8.8) and caused dehydration in 85% of the cases (Lamberti et al., 2012). The goals of treatment are to prevent or reverse dehydration, to shorten the duration of the illness, and to reduce the period during which a person is infectious (Guarino et al., 2020).
The use of multispecies (multistrain) synbiotic mixtures in children with diarrhoea have shown beneficial effects, particularly in improving the course of the episode, reducing the duration of diarrhoea and length of hospital stay in children requiring in-patient care (Dinleyici et al., 2013). In multistrain synbiotic products, the probiotic effect is improved thanks to the combination of specific properties of the strains (additive and synergistic effect) (Pandey et al., 2015; Timmerman et al., 2004). In the present study, the synbiotic product was a 7-strain synbiotic available as drops to be administered over 7 consecutive days. Also, it is important to note the value of the prebiotic in the composition of the synbiotic product. The prebiotic contributes to the growth of the probiotic and the beneficial bacteria that inhabit the intestinal tract (Pandey et al., 2015; Timmerman et al., 2004).
The target population included children ≤2 years of age presenting with acute diarrhoea and associated symptoms of less than 48 h of evolution and of a probable viral aetiology. Treatment with the synbiotic product was added to standard treatment based on oral rehydration and/or diet and was compared to supportive treatment alone. In comparison with the control group, various benefits associated to the complementary use of the synbiotic product included a significantly lower percentage of children with diarrhoea (defined as ≥3 bowel movements during ≥3 consecutive days), reduction of two days in the duration of diarrhoea, decrease in the percentage of children with diarrhoea during each day over the study period from day three until the end of treatment, decrease in the days of diarrhoea as evaluated by the parents and higher diarrhoea recovery rate. The synbiotic demonstrated a rapid onset of effect, with differences in efficacy since day two of therapy, being statistically significant from day three until the end of treatment. The results of our study are consistent with shortened duration of diarrhoea with the use of probiotics as compared with placebo reported in systematic reviews and meta-analysis (Alsabri et al., 2025; Applegate et al., 2023; Li et al., 2021; Yang et al., 2019). Also, in a previous randomised clinical study of a sachet formulation of the synbiotic product administered to patients with diarrhoea aged 6 months to 12 years, there was a significant improvement in diarrhoea-related outcomes as compared with standard supportive treatment (Garcı́a-Menor et al., 2016). Also, in the group of children aged 6 months to 2 years, the duration of diarrhoea was shortened by two days (Garcı́a-Menor et al., 2016), which is consistent with results of the present study.
All these findings are clinically relevant in children younger than two years because of the vulnerability of toddlers at this age, who are more susceptible to dehydration and related symptoms than older children. On the other hand, a 2-day reduction in the duration of diarrhoea has an important social impact for parents and caregivers due to early nursery attendance, less days of childcare, and parenteral absenteeism to work. Likewise, effective interventions capable of reducing the duration of diarrhoea (and the need for hospitalisation) in special populations such as undernourished children would have an enormous impact in resource-poor settings (Kambale et al., 2021).
Compliance with the synbiotic drops was excellent and 95% of parents would recommend the product for the management of similar episodes of diarrhoea. There were no safety concerns and most common events were related to the gastrointestinal tract, such as vomiting, abdominal discomfort, and mucous stools.
The present results should be interpreted considering some limitations, such as the open-label design of the study. However, the use of a placebo instead of a synbiotic product could be an approach not easily accepted by parents at the time of providing consent. Children presented with diarrhoea of probable viral origin but the types of viral etiologies were not recorded. On the other hand, PRODINFANT study was a multicentre trial, following diarrhoea treatment aligned to real clinical practice disease management, which strengthens the generalisability of our findings. The results of PRODINFANT study are aligned to the benefits of synbiotic treatment already observed in Garcı́a-Menor E et al. (2016).
5 Conclusions
The 7-multistrain synbiotic formulation evaluated in PRODINFANT study, administered as oral drops, provided clinically relevant benefits to supportive measures (diet and/or oral rehydration) for improving diarrhoea-related outcomes in children of two years of age or younger. The use of the synbiotic product was associated with a rapid improvement of symptoms and reduction of duration of diarrhoea by two days, which is clinically relevant for the children themselves, as well as to the parents/tutors regarding absenteeism from work and other aspects of daily life. The synbiotic product also promoted a faster complete recovery. Synbiotic therapy significantly improved the evolution of the diarrhoea in children <2 years, providing additional benefit to standard supportive measures in the management of diarrhoea. These results along a very favourable safety and tolerability profile supports the use of this synbiotic in acute diarrhoea of probable viral etiology.
Corresponding author; e-mail: e.garcia@italfarmacogroup.com
Authors’ contribution
Conceptualisation, EGA; methodology, EGA; formal analysis, FGM, PCT, AMA, MAMC, MJLP, LPA, EGM and EGA; investigation, FGM, PCT, AMA, MAMC, MJLP, LPA, EGM and EGA; writing (original draft preparation), EGA; writing (review and editing), FGM, PCT, AMA, MAMC, MJLP, LPA, EGM and EGA. All authors have read and agreed to the published version of the manuscript. The authors decline the use of artificial intelligence, language models, machine learning, or similar technologies to create content or assist with writing or editing of the manuscript.
Conflict of interest
EGA is a full-time employee of ITF Research Pharma SLU. The rest of authors declare no conflict of interest.
Data availability
Study data are available from the corresponding author upon request.
Funding
This study was funded by ITF Research Pharma S.L.U.
Trial registration
ISRCTN10495554.
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