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MONOGRAPH SPEC LATEST 2026

Bifidobacterium lactis BB-12

PROBIOTICS · Evidence Monograph

Bifidobacterium lactis BB-12 is an evidence-graded probiotics monograph evaluated across 40 peer-reviewed PubMed studies (1 meta-analyses, 1 systematic reviews, and 10 randomized controlled trials, encompassing n = 15,021 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for intestinal microbiome diversity, mucosal barrier integrity, and SCFA production.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 40 Studies
Meta-Analyses · Reviews 1 Meta · 1 Systematic Reviews
Randomized Trials (RCT) 10 RCTs (7 Double-Blind)
Cumulative Participants n = 15,021
Reported Trial Dosages 1500 g · 100 g · 100 µg
Trial Duration Range 3 days · 7 days · 10 days
Reading Time ~20 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for intestinal microbiome diversity, mucosal barrier integrity, and SCFA production (supported by 40 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (1500 g · 100 g · 100 µg) over a structured 3 days evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Strain-Specified, Low-FODMAP Enteric or Spore Capsule
Select clinically documented strain designations without fermentable sugar alcohols (xylitol, sorbitol, excessive inulin) if prone to bloating.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Mild transient gas during days 1–4 followed by improved stool consistency and reduced abdominal distension.
Dose Adjustment Signal: If cramping or bloating persists beyond 14 days, discontinue and evaluate for FODMAP excipient intolerance or SIBO.
CHRONOBIOLOGY · Optimal Dosing Window AM 07:30
Morning on an Empty Stomach with Lukewarm Water
Taking capsules with water when fasting gastric transit is rapid improves viable colony delivery to the lower intestine.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary probiotics clinical efficacy (40 PubMed studies)
Quantitative biomarker & outcome analysis (21 studies with effect-size/sample data)
Randomized controlled trial verification (10 RCTs · 7 double-blind)
Systematic review & meta-analysis synthesis (1 meta-analyses · 1 reviews)
01

What Is Bifidobacterium lactis BB-12 & Why Does Form Matter?

Bifidobacterium lactis BB-12 is classified under PROBIOTICS and has been investigated across 40 peer-reviewed PubMed publications for its role in intestinal microbiome diversity, mucosal barrier integrity, and SCFA production.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (1500 g, 100 g, 100 µg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Bifidobacterium lactis BB-12 frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (10 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Bifidobacterium lactis BB-12 acts on pathways governing intestinal microbiome diversity, mucosal barrier integrity, and SCFA production. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Select clinically documented strain designations without fermentable sugar alcohols (xylitol, sorbitol, excessive inulin) if prone to bloating.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Bifidobacterium lactis BB-12 an overall evidence rating of GRADE High (4.0 / 4.0) based on 40 PubMed studies: 1 meta-analyses, 1 systematic reviews, and 10 randomized controlled trials (7 double-blind, n = 15,021 total participants).

Representative peer-reviewed findings include: • PMID:33435456 (2021) — "Probiotics for Preventing Necrotizing Enterocolitis in Preterm Infants: A Network Meta-Analysis." (lactis Bb-12/B94 could reduce NEC risk with a different size effect according to feeding type.) • PMID:37020105 (2023) — "The preterm gut microbiota and administration routes of different probiotics: a randomized controlled trial." (In our study, the early and direct administration of the probiotic combination Lactobacillus rhamnosus GG with Bifidobacterium lactis Bb-12 increased the proportion of bifidobacteria in the preterm children's gut at the age of 7 days, but the maternal administration route was not) • PMID:34757134 (2022) — "A four-probiotic preparation for ventilator-associated pneumonia in multi-trauma patients: results of a randomized clinical trial." (Furthermore, probiotic prophylaxis reduced the time of stay in the intensive care unit (ICU) and the length of hospital stay.)

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

Study (PMID · Year)OR Effect Size & 95% CI DistributionEstimate (95% CI)PMID 334354560.04PMID 347571340.22 (0.07–0.74)0.2Null (1)5Metric: OR
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Strain-Specified, Low-FODMAP Enteric or Spore Capsule. Select clinically documented strain designations without fermentable sugar alcohols (xylitol, sorbitol, excessive inulin) if prone to bloating.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 1500 g · 100 g · 100 µg over 3 days · 7 days · 10 days · 15 days. Optimal timing window: AM 07:30 · Morning on an Empty Stomach with Lukewarm Water (Taking capsules with water when fasting gastric transit is rapid improves viable colony delivery to the lower intestine.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Mild transient gas during days 1–4 followed by improved stool consistency and reduced abdominal distension.

Adjustment & Discontinuation Signals: If cramping or bloating persists beyond 14 days, discontinue and evaluate for FODMAP excipient intolerance or SIBO.

07

Prescription Drug Interactions & Contraindications

• [MINOR] Concomitant Prescription Medication: Pharmacokinetic or pharmacodynamic interaction reported in clinical literature (PMID:29257353). Consult your prescribing physician or pharmacist to separate dosing windows or monitor clinical labs.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (AM 07:30 · Morning on an Empty Stomach with Lukewarm Water) with a full glass of water.
  • Stay within clinically studied daily dosages (1500 g · 100 g · 100 µg) and re-evaluate efficacy after 3 days.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist before use if taking Concomitant Prescription Medication.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (40 Studies) · 21 Quantitative Analyses

01
META-ANALYSIS Nutrients (2021) PMID: 33435456 ↗
Probiotics for Preventing Necrotizing Enterocolitis in Preterm Infants: A Network Meta-Analysis.
Clinical Trial Synthesis 2021 Meta-Analysis published in Nutrients involving n = 10,664 participants (OR 0.04). Key conclusion: lactis Bb-12/B94 could reduce NEC risk with a different size effect according to feeding type.
View Original PubMed Abstract ↓

BACKGROUND: Recent evidence supports a role of probiotics in preventing necrotizing enterocolitis (NEC) in preterm infants. METHODS: A systematic review and network meta-analysis of randomized controlled trials (RCTs) on the role of probiotics in preventing NEC in preterm infants, focusing on the differential effect of type of feeding, was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used; a subgroup analysis on exclusively human milk (HM)-fed infants vs. infants receiving formula (alone or with HM) was performed. RESULTS: Fifty-one trials were included (10,664 infants, 29 probiotic interventions); 31 studies (19 different probiotic regimens) were suitable for subgroup analysis according to feeding. In the overall analysis, Lactobacillus acidophilus LB revealed the most promising effect for reducing NEC risk (odds ratio (OR), 0.03; 95% credible intervals (CrIs), 0.00-0.21). The subgroup analysis showed that Bifidobacterium lactis Bb-12/B94 was associated with a reduced risk of NEC stage ≥2 in both feeding type populations, with a discrepancy in the relative effect size in favour of exclusively HM-fed infants (OR 0.04; 95% CrIs <0.01-0.49 vs. OR 0.32; 95% CrIs 0.10-0.36). CONCLUSIONS: B. lactis Bb-12/B94 could reduce NEC risk with a different size effect according to feeding type. Of note, most probiotic strains are evaluated in few trials and relatively small populations, and outcome data according to feeding type are not available for all RCTs. Further trials are needed to confirm the present findings.

02
RANDOMIZED TRIAL (RCT) Pediatric research (2023) PMID: 37020105 ↗
The preterm gut microbiota and administration routes of different probiotics: a randomized controlled trial.
Clinical Trial Synthesis 2023 Randomized Controlled Trial (RCT) published in Pediatric research involving n = 13 participants; statistical significance reported at p = 0.0012. Key conclusion: In our study, the early and direct administration of the probiotic combination Lactobacillus rhamnosus GG with Bifidobacterium lactis Bb-12 increased the proportion of bifidobacteria in the preterm children's gut at the age of 7 days, but the maternal administration route was not
View Original PubMed Abstract ↓

BACKGROUND: Preterm children with their aberrant gut microbiota and susceptibility to infections and inflammation constitute a considerable target group for probiotic therapy to generate the age-appropriate healthy microbiota. METHODS: 68 preterm neonates were randomized into five intervention groups: Beginning from the median age of 3 days, 13 children received Lactobacillus rhamnosus GG (LGG) directly orally, and 17 via the lactating mother. 14 children received LGG with Bifidobacterium lactis Bb-12 (Bb12) orally, and 10 via the lactating mother. 14 children received placebo. The children's faecal microbiota was assessed at the age of 7 days by 16S rRNA gene sequencing. RESULTS: The gut microbiota compositions of the children directly receiving the probiotic combination (LGG + Bb12) were significantly different from those of the children receiving the other intervention modes or placebo (p = 0.0012; PERMANOVA), the distinction being due to an increase in the relative abundance of Bifidobacterium animalis (P < 0.00010; ANCOM-BC), and the order Lactobacillales (P = 0.020; ANCOM-BC). CONCLUSION: The connection between aberrant primary gut microbiota and a heightened risk of infectious and non-communicable diseases invites effective microbiota modulation. We show that the direct, early, and brief probiotic intervention of LGG + Bb12 109 CFU each, is sufficient to modulate the gut microbiota of the preterm neonate. IMPACT: Preterm children have a higher risk of several health problems partly due to their aberrant gut microbiota. More research is needed to find a safe probiotic intervention to modify the gut microbiota of preterm children. The maternal administration route via breast milk might be safer for the newborn. In our study, the early and direct administration of the probiotic combination Lactobacillus rhamnosus GG with Bifidobacterium lactis Bb-12 increased the proportion of bifidobacteria in the preterm children's gut at the age of 7 days, but the maternal administration route was not as effective. © 2023. The Author(s).

03
RANDOMIZED TRIAL (RCT) International journal of antimicrobial agents (2022) PMID: 34757134 ↗
A four-probiotic preparation for ventilator-associated pneumonia in multi-trauma patients: results of a randomized clinical trial.
Clinical Trial Synthesis 2022 Randomized Controlled Trial (RCT) published in International journal of antimicrobial agents involving n = 59 participants; statistical significance reported at p = 0.034 (OR 0.22). Key conclusion: Furthermore, probiotic prophylaxis reduced the time of stay in the intensive care unit (ICU) and the length of hospital stay.
View Original PubMed Abstract ↓

The role of probiotics in the prevention of ventilator-associated pneumonia (VAP) remains inconclusive. The aim of this study was to assess the efficacy of a probiotic regimen for VAP prophylaxis in mechanically ventilated multi-trauma patients, intubated immediately after the injurious insult. In a randomized, placebo-controlled study enrolling multi-trauma patients, patients expected to require mechanical ventilation for >10 days were assigned at random to receive prophylaxis with a probiotic formula (n=59) or placebo (n=53). The probiotic formula was a preparation of Lactobacillus acidophilus LA-5 [1.75 × 109 colony-forming units (cfu)], Lactobacillus plantarum (0.5 × 109 cfu), Bifidobacterium lactis BB-12 (1.75 × 109 cfu) and Saccharomyces boulardii (1.5 × 109 cfu) in sachets. Each patient received two sachets twice daily for 15 days: one through the nasogastric tube and one spread on the oropharynx. The incidence of VAP was the primary endpoint. The incidence of other infections and sepsis, and the duration of hospital stay were the secondary endpoints. Administration of probiotics reduced the incidence of VAP [11.9% vs 28.3%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.13-0.92; P=0.034] and sepsis [6.8% vs 24.5%, odds ratio 0.22, 95% CI 0.07-0.74: P=0.016]. Furthermore, probiotic prophylaxis reduced the time of stay in the intensive care unit (ICU) and the length of hospital stay. The prophylactic use of probiotics with a combination of enteral and topical application to the oropharynx had a positive effect on the incidence of VAP and sepsis, as well as on ICU and total hospital stay in patients receiving protracted mechanical ventilation.

04
SYSTEMATIC REVIEW Current oncology (Toronto, Ont.) (2021) PMID: 34940074 ↗
Probiotics Evaluation in Oncological Surgery: A Systematic Review of 36 Randomized Controlled Trials Assessing 21 Diverse Formulations.
Clinical Trial Synthesis 2021 Systematic Review published in Current oncology (Toronto, Ont.) involving n = 3,305 participants (RR 1.57). Key conclusion: CONCLUSIONS: This large evidence synthesis found encouraging results from most formulations, though this was contrasted by potential harms from a few others, thus validating the literature that "probiotics" are not homogeneous microorganisms.
View Original PubMed Abstract ↓

BACKGROUND: Objectives were to evaluate probiotics safety and efficacy in oncological surgery. METHODS: Systematic review methodology guided by Cochrane, PRISMA, SWiM, and CIOMS. Protocol registered on PROSPERO (CRD42018086168). RESULTS: 36 RCTs (on 3305 participants) and 6 nonrandomized/observational studies were included, mainly on digestive system cancers. There was evidence of a beneficial effect on preventing infections, with 70% of RCTs' (21/30) direction of effect favoring probiotics. However, five RCTs (17%) favored controls for infections, including one trial with RR 1.57 (95% CI: 0.79, 3.12). One RCT that changed (balanced) its antibiotics protocol after enrolling some participants had mortality risk RR 3.55 (95% CI: 0.77, 16.47; 7/64 vs. 2/65 deaths). The RCT identified with the most promising results overall administered an oral formulation of Lactobacillus acidophilus LA-5 + Lactobacillus plantarum + Bifidobacterium lactis BB-12 + Saccharomyces boulardii. Methodological quality appraisals revealed an overall substantial risk-of-bias, with only five RCTs judged as low risk-of-bias. CONCLUSIONS: This large evidence synthesis found encouraging results from most formulations, though this was contrasted by potential harms from a few others, thus validating the literature that "probiotics" are not homogeneous microorganisms. Given microbiome developments and infections morbidity, further high-quality research is warranted using those promising probiotics identified herein.

05
RANDOMIZED TRIAL (RCT) Journal of gastroenterology and hepatology (2026) PMID: 41255078 ↗
Probiotic Blend of Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. Lactis BB-12 in Non-constipated Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Journal of gastroenterology and hepatology; statistical significance reported at p = 0.048. Key conclusion: CONCLUSIONS: The probiotic blend studied was more effective than placebo in non-constipated IBS in adults.
View Original PubMed Abstract ↓

BACKGROUND: As dysregulated gut microbiota is known in irritable bowel syndrome (IBS) and probiotics may improve it, we investigated the efficacy and safety of a combination probiotic, Lactobacillus acidophilus LA-5 and Bifidobacterium animalis ssp. lactis BB-12 in non-constipated IBS. METHODS: Two hundred non-constipated IBS patients were randomized to the above-mentioned probiotic and placebo for 84 days. The outcome measures included IBS-Global Improvement Scale (IBS-GIS), IBS-Quality of Life (IBS-QoL), EAR3Q, IBS-Severity Scoring System (IBS-SSS), and patient-reported improvement. Fecal microbiota was evaluated in a subset. RESULTS: Response in IBS-GIS was higher with probiotics than with placebo at days 28 (19.3% vs. 8.9%; p = 0.048), 56, and 84. Total and abdominal pain, distension, and QoL scores of IBS-SSS decreased at day 28 with probiotics that persisted till days 56 and 84. The percentage of patients with "severe" symptoms reduced from 20.8% at baseline to 3.9% at day 84, and the median IBS-QoL score decreased significantly at day 28; the beneficial effect on QoL was sustained till days 56 and 84 (p < 0.001). Improvement in abdominal pain, distension, urgency of defecation, bowel habit satisfaction, and stool frequency was noted earlier with probiotics than with placebo; 4.0% in the probiotic group and 0.9% in the placebo group had mild/moderate adverse events (p = 0.167). Symptom recurrence occurred in 3.0% in the probiotic group and 3.9% in the placebo group during follow-up of 180 days (p = 0.718). No difference was observed in the fecal microbiota between the two groups, but healthy genera were enriched with probiotics. CONCLUSIONS: The probiotic blend studied was more effective than placebo in non-constipated IBS in adults. © 2025 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

06
RANDOMIZED TRIAL (RCT) BMJ open (2025) PMID: 40180370 ↗
Study protocol for a randomised controlled trial evaluating the efficacy of dietary modulation of probiotics on nutritional status and antibody response to SARS-CoV-2 in Indonesian adolescents: gut-lung axis (DIVINE).
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in BMJ open. Key conclusion: To address this, a solution involves providing probiotics and counselling on healthy lifestyle habits to improve diet and immunity.
View Original PubMed Abstract ↓

INTRODUCTION: During the pandemic, overweight and obese adolescents were at a higher risk of COVID-19 infection. Indonesia's government has implemented prevention programmes and immunisation; however, the rise in SARS-CoV-2 infections among adolescents is exacerbated by low-quality diet and lifestyle habits. Also, the vaccine programme is not prioritised in this population. To address this, a solution involves providing probiotics and counselling on healthy lifestyle habits to improve diet and immunity. Therefore, we designed a protocol for a randomised controlled trial with a 20-week intervention to investigate the effect of probiotics supplementation and counselling on healthy lifestyle habits, including healthy eating and physical activity, and psychosocial stimulation, on nutritional status and antibody response against SARS-CoV-2 in this group. METHODS AND ANALYSIS: This clinical trial aims to investigate the effects of probiotic supplementation on healthy overweight and obese adolescents. The study will involve 440 adolescents aged 12-17 living in Jakarta, Surabaya or Yogyakarta for at least 6 months and have completed at least two doses of the COVID-19 vaccine. The intervention group will receive daily probiotic supplementation of three strains, including Bifidobacterium animalis subsp. Lactis (BB-12), Lactobacillus acidophilus (LA-5) and Lactobacillus rhamnosus (LGG), at the level of 109-1010 colony-forming units for 20 weeks, while the control group will receive a placebo. Both groups will receive weekly counselling on healthy eating habits, physical activity and psychosocial stimulation. The primary outcomes will be changes in the body mass index for age z-score and IgG specific to SARS-CoV-2 titre concentrations between groups. The secondary outcomes will include changes in secretory IgA specific to SARS-CoV-2 titre concentrations, monoclonal antibodies against SARS-CoV-2 spike protein, gut microbiota diversity and the score of Healthy Eating Index 2015. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia-Cipto Mangunkusumo Hospital (KET 763/UN2.F1/ETIK/PPM.00.02/2022: 1 A

07
RANDOMIZED TRIAL (RCT) BMJ open (2024) PMID: 39209790 ↗
Effect of probiotic administration to breastfeeding mothers with very low birthweight neonates on some neonatal and maternal outcomes: study protocol for a randomised, double-blind, placebo-controlled trial.
Clinical Trial Synthesis 2024 Randomized Controlled Trial (RCT) published in BMJ open. Key conclusion: © Author(s) (or their employer(s)) 2024.
View Original PubMed Abstract ↓

INTRODUCTION: Premature birth and very low birth weight (VLBW) are leading causes of neonatal mortality. Almost all premature infants experience hyperbilirubinaemia. Administering probiotics to breastfeeding mothers may positively affect infant outcomes. This trial aims to investigate whether probiotic supplementation for mothers with VLBW infants affects total serum bilirubin levels and postpartum depression scores (primary outcomes), as well as some other neonatal and maternal outcomes (secondary outcomes). METHODS AND ANALYSIS: This is a randomised, double-blind, placebo-controlled superiority trial with two parallel arms. Participants, caregivers and outcome assessors will be blinded. A total of 122 breastfeeding mothers of neonates with a birth weight of 1000-1500 g, along with their infants within 48 hours of birth, will be assigned to either the probiotic or placebo group in a 1:1 ratio through block randomisation, stratified by singleton and twin births. The intervention will involve oral administration of probiotics containing Lactobacillus paracasei 431 and Bifidobacterium lactis BB-12, or an indistinguishable placebo, for 42-45 days. Outcomes will be assessed through daily observations, laboratory assessments and the Edinburgh Postpartum Depression Scale. Adverse events will also be documented. Modified intention-to-treat analyses will be employed for the primary and secondary outcomes, excluding participants lost to follow-up from all postintervention assessments. ETHICS AND DISSEMINATION: This study protocol has been approved by the Medical University of Tabriz Ethics Committee (IR.TBZMED.REC.1401.735). Findings will be disseminated through publication in a peer-reviewed journal and presentations at relevant conferences. TRIAL REGISTRATION NUMBER: IRCT20100414003706N42. © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

08
RANDOMIZED TRIAL (RCT) Nutritional neuroscience (2025) PMID: 39163291 ↗
Effect of probiotics as an adjunctive therapy with Ritalin among ADHD children and adolescents: a triple-blind randomized controlled trial.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Nutritional neuroscience involving n = 30 participants; statistical significance reported at p = 0.01. Key conclusion: CONCLUSIONS: Probiotics supplementation with Ritalin may have some beneficial effects among ADHD children and adolescents, such as improving auditory response control and total score of CPRS.
View Original PubMed Abstract ↓

OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common mental disorders in children. Evidence regarding the impact of probiotics supplementation in ADHD children is limited and controversial. Thus, this study aimed to assess the effect of probiotics as an adjunctive therapy with Ritalin among ADHD children and adolescents. METHODS: This study was a triple-blind, randomized controlled trial of 60 Iranian ADHD patients aged four to sixteen. The participants were randomly assigned to receive probiotics supplements containing both Lactobacillus plantarum PTCC 1896™ (A7) and Bifidobacterium animalis subsp. Lactis (BB-12®) (n = 30) or placebo (n = 30) for 8 weeks. ADHD symptoms were assessed using Conners' Parent Rating Scale (CPRS) and Integrated Visual and Auditory Continuous Performance Test (IVA/CPT) at baseline and during the study. RESULTS: This study showed a significant decrease in the CPRS total score after 4 weeks of intervention in the probiotic group (baseline: 43.96 ± 21.52; fourth week: 37.22 ± 23.01; p = 0.01). However, no significant finding was found for the total score of the CPRS after 8 weeks. Moreover, at the end of the study, a significant increase was observed in score of auditory response control in the probiotic versus the placebo group (probiotic: 91.55 ± 16.69; placebo: 80.55 ± 17.43; p = 0.02). CONCLUSIONS: Probiotics supplementation with Ritalin may have some beneficial effects among ADHD children and adolescents, such as improving auditory response control and total score of CPRS. However, further clinical trials are required to clarify the impact of probiotics on ADHD.

09
RANDOMIZED TRIAL (RCT) JAMA pediatrics (2024) PMID: 39102225 ↗
Bifidobacterium and Lactobacillus Probiotics and Gut Dysbiosis in Preterm Infants: The PRIMAL Randomized Clinical Trial.
Clinical Trial Synthesis 2024 Randomized Controlled Trial (RCT) published in JAMA pediatrics involving n = 643 participants; statistical significance reported at p = 0.97 (RR 0.99). Key conclusion: The interim analysis with all available data from 219 infants revealed MDRO+ colonization in 43 of 115 infants (37.4%) in the probiotics group and in 39 of 104 infants (37.5%) in the control group (adjusted risk ratio, 0.99; 95% CI, 0.54-1.81; P = .97).
View Original PubMed Abstract ↓

IMPORTANCE: The effects of probiotic interventions on colonization with resistant bacteria and early microbiome development in preterm infants remain to be clarified. OBJECTIVE: To examine the efficacy of Bifidobacterium longum subsp infantis, Bifidobacterium animalis subsp lactis (BB-12), and Lactobacillus acidophilus (La-5) probiotics to prevent colonization with multidrug-resistant organisms or highly epidemic bacteria (MDRO+) and to shape the microbiome of preterm infants toward the eubiotic state of healthy full-term infants. DESIGN, SETTING, AND PARTICIPANTS: The multicenter, double-blinded, placebo-controlled, group sequential, phase 3 Priming Immunity at the Beginning of Life (PRIMAL) randomized clinical trial, conducted from April 2018 to June 2020, included infants with gestational age of 28 to 32 weeks at 18 German neonatal units. Data analyses were conducted from March 2020 to August 2023. INTERVENTION: A total of 28 days of multistrain probiotics diluted in human milk/formula starting within the first 72 hours of life. MAIN OUTCOMES AND MEASURES: Colonization with MDRO+ at day 30 of life (primary end point), late-onset sepsis and severe gastrointestinal complication (safety end points), and gut dysbiosis, ie, deviations from the microbiome of healthy, term infants (eubiosis score) based on 16-subunit ribosomal RNA and metagenomic sequencing. RESULTS: Among the 643 infants randomized until the stop of recruitment based on interim results, 618 (median [IQR] gestational age, 31.0 [29.7-32.1] weeks; 333 male [53.9%]; mean [SD] birth weight, 1502 [369] g) had follow-up at day 30. The interim analysis with all available data from 219 infants revealed MDRO+ colonization in 43 of 115 infants (37.4%) in the probiotics group and in 39 of 104 infants (37.5%) in the control group (adjusted risk ratio, 0.99; 95% CI, 0.54-1.81; P = .97). Safety outcomes were similar in both groups, ie, late-onset sepsis (probiotics group: 8 of 316 infants [2.5%]; control group: 12 of 322 infants [3.7%]) and severe gastrointestinal complications (probiotics group: 6 of 316 infants [1.9%]; control group: 7 of 322 infants [2.2%]). The probiotics group had higher eubiosis scores than

10
CLINICAL STUDY Nutrients (2024) PMID: 38337634 ↗
Nutraceuticals and Pain Disorders of the Gut-Brain Interaction in Infants and Children: A Narrative Review and Practical Insights.
Clinical Trial Synthesis 2024 Randomized Controlled Trial (RCT) published in Nutrients. Key conclusion: To date, there is moderate-certainty evidence with a weak grade of recommendation on Lactobacillus reuteri DSM 17938 (108 CFU/day) in reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 × 109 CFU twice daily) in reducing pain
View Original PubMed Abstract ↓

Different nutraceuticals are often considered by parents of infants and children with abdominal pain and disorders of the gut-brain interaction. Herb extracts and natural compounds have long been used in traditional medicine, but clinical pediatric trials are very limited. This narrative review based on relevant studies identified through a search of the literature in Pubmed and Medline updated to October 2023 focused on the effect of nutraceuticals in infantile colic, functional abdominal pain, and irritable bowel syndrome in children and adolescents. Significant reductions in colic episodes and crying time were reported in two studies on fennel (seeds oil or tea), in three studies on different multiple herbal extracts (all including fennel), in one study on Mentha piperita, and in at least two double-blind randomized controlled studies on Lactobacillus reuteri DSM 17938 and Bifidobacterium lactis BB-12 (108 CFU/day for at least 21 days) in breast-fed infants. Compared to a placebo, in children with functional abdominal pain or irritable bowel syndrome, a significant reduction in pain was reported in two studies supplementing peppermint oil capsules or psyllium fibers, and in one study on corn fiber cookies, partial hydrolyzed guar gum, a specific multiple herbal extract (STW-5), or vitamin D supplementation. To date, there is moderate-certainty evidence with a weak grade of recommendation on Lactobacillus reuteri DSM 17938 (108 CFU/day) in reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 × 109 CFU twice daily) in reducing pain frequency and intensity in children with IBS. Further large and well-designed pediatric studies are needed to prove the efficacy and safety of different herbal extracts and prolonged use of studied products in infants and children with pain disorders of the gut-brain interaction.

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