Next Article in Journal
The Effect of Intradialytic Exercise Using Virtual Reality on the Body Composition of Patients with Chronic Kidney Disease
Next Article in Special Issue
The Effectiveness of Heat-Killed Pediococcus acidilactici K15 in Preventing Respiratory Tract Infections in Preterm Infants: A Pilot Double-Blind, Randomized, Placebo-Controlled Study
Previous Article in Journal
Diet Quality and Risk of Bladder Cancer in the Multiethnic Cohort Study
Previous Article in Special Issue
Limosilactobacillus vaginalis Exerts Bifidogenic Effects: A Novel Postbiotic Strategy for Infant Prebiotic Supplementation
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Nutrients
Volume 16
Issue 12
10.3390/nu16121967
nutrients-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Effects of Bifidobacterium longum 35624 in Children and Adolescents with Irritable Bowel Syndrome

by
Sylvia Cruchet Muñoz
1,
Sandra Verbeke Palma
2,*,
Lydia Lera Marqués
3,
María Nelly Espinosa Pizarro
4,5,
Jacqueline Malig Mechasqui
6 and
Katy Sorensen
7
1
Instituto de Nutrición y Tecnología de los Alimentos “Dr. Fernando Monckeberg”, Área Nutrición Humana, Universidad de Chile, El Líbano 5524, Macul, Santiago 7830490, Chile
2
Escuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Campus Santiago, Chile. Av. Ejército 146, Santiago 8370003, Chile
3
Faculty of Graduate Business and Education Programs, Keiser University eCampus, 1900 West Commercial Boulevard. Ste 100, Ft. Lauderdale, FL 33309, USA
4
Facultad de Medicina, Universidad de los Andes, Monseñor Álvaro del Portillo 12455, Las Condes, Santiago 7620001, Chile
5
Hospital Militar de Santiago, Av. Fernando Castillo Velasco 9100, La Reina, Santiago 7880047, Chile
6
Clínica Red Salud Vitacura de Santiago, Tabancura 1141, Vitacura, Santiago 7650018, Chile
7
Medical Affairs, Novozymes A/S, Krogshøjvej 36, 2880 Bagsvaerd, Denmark
*
Author to whom correspondence should be addressed.
Nutrients 2024, 16(12), 1967; https://doi.org/10.3390/nu16121967
Submission received: 28 May 2024 / Revised: 14 June 2024 / Accepted: 17 June 2024 / Published: 20 June 2024
(This article belongs to the Special Issue Probiotics and Prebiotics in Pediatrics)
Browse Figures
Versions Notes

Highlights

  • Probiotic supplementation with Bifidobacterium longum 35624 reduced IBS symptoms and impact on daily life, indicating positive effects on quality of life.
  • There was a high response rate of participants to probiotic supplementation, with >93% experiencing clinically significant improvements in IBS-SSS.
  • The distribution of IBS severity categories changed during probiotic supplementation, with decreases in the proportion of participants with severe or moderate symptoms and increases in those with mild symptoms or in remission.
  • Following cessation of probiotic supplementation, composite IBS-SSS scores significantly increased, suggesting that a longer intake period may be necessary to maintain beneficial results.

Abstract

:
Irritable bowel syndrome (IBS) and vitamin D deficiency are common among children in Latin America. Previous studies show that Bifidobacterium longum 35624TM improves IBS symptoms in adults. This real-world, single-arm, open-label study conducted in Chile investigated the effects of B. longum 35624 (1 × 109 colony-forming units, 12 weeks) on gastrointestinal symptoms (adapted IBS severity scoring system [IBS-SSS]; adapted Questionnaire on Pediatric Gastrointestinal Symptoms [QPGS], and Bristol Stool Form Scale) in 64 children and adolescents (8–18 years) and explored the relationship with baseline vitamin D status. Improvements in all IBS-SSS domains and composite score were observed at week 6 and 12 (p < 0.0007 versus baseline), with 98.3% of participants experiencing numerical improvements in ≥3 domains. Clinically meaningful improvement was seen in 96.6% of participants. The distribution of IBS-SSS severity categories shifted from moderate/severe at baseline to mild/remission (p < 0.0001). Improvements were not maintained during the two-week washout. Low baseline serum vitamin D levels did not correlate to IBS severity or probiotic response. QPGS significantly decreased from baseline to week 6 (p = 0.0005) and 12 (p = 0.02). B. longum 35624 may improve IBS symptoms in children and adolescents, even those with vitamin D deficiency. A confirmatory randomized controlled trial and further exploration of probiotic response and vitamin D status are needed.

1. Introduction

Disorders of gut–brain interaction (DGBI), formerly referred to as functional gastrointestinal disorders (FGIDs), are characterized by recurrent gastrointestinal (GI) symptoms unrelated to organic disease [1]. Often presenting concurrently in childhood [2], DGBI may affect 22% of children worldwide [3] and 12–48% in Latin America [4]. Irritable bowel syndrome (IBS) is among the most common DGBI in children over four years of age [3].
IBS is characterized by recurrent abdominal pain associated with defecation and/or changes in stool form or frequency [5]. Its etiology is complex, involving gut dysmotility, visceral hypersensitivity, altered mucosal and immune responses, central nervous system processing, and gut microbiota composition [1]. Mucosal inflammation triggered by infectious gastroenteritis may induce the de novo onset of IBS in some cases (post-infection IBS; PI-IBS) [1,6]. PI-IBS provides a paradigm for how microbiome–host interactions may play a role in IBS, in general. Serum vitamin D levels have been found to be lower in people with IBS than those without, with a high incidence of deficiency in IBS populations. resulting, perhaps, in a pro-inflammatory state given the anti-inflammatory properties of this vitamin [7]. Whilst the immunoregulatory activity of some microorganisms has prompted growing interest in the use of probiotics in IBS [8], effects are likely strain-specific [9,10].
Bifidobacterium longum 35624 has been shown to survive gastrointestinal transit, inhibit the growth of pathogenic organisms, prevent bacterial translocation, and exert anti-inflammatory effects [11,12]. Double-blind, placebo-controlled trials found that this strain reduced GI symptoms in adults with IBS [11,13]. Anecdotal reports from South America suggest that supplementation with this strain occurs in pediatric clinical practice. Whilst its safety has been confirmed in a pediatric population [14], data demonstrating its effectiveness among children with IBS has not been published. This real-world, open-label study conducted in Chile aimed to investigate the effects of Bifidobacterium longum 35624 on GI symptoms in children and adolescents with IBS and explore the relationship with baseline vitamin D status.

2. Materials and Methods

Ethical approval for this open-label, single-arm clinical study was obtained from the Scientific Ethics Committee of the Institute of Nutrition and Food Technology, University of Chile, and registered on clinicaltrials.gov (NCT04922476). Potential participants were identified in gastroenterology clinics by their managing physician and referred to the study physician. Children and adolescents aged 8–18 years old residing in Santiago and Coyhaique, Chile, were considered for inclusion if they met the Rome IV diagnostic criteria [5] for IBS (with or without other DGBI), reported at least two episodes of abdominal pain per week, and had moderate to severe disease severity according to the IBS severity scoring system (IBS-SSS) [15,16]. Individuals were excluded if they had systemic, organic or metabolic disease (including celiac disease), history of previous major abdominal surgery, immunosuppression, or a known allergy to any ingredients of the probiotic supplement; were pregnant or lactating; used proton-pump inhibitors, histamine type-2 receptor antagonists, fermented foods or dietary supplements containing probiotics within two weeks before the baseline visit, or antibiotics within three months before the baseline visit; or had participated in a clinical study involving an investigational product within the last two months.
Written informed consent was obtained for each potentially eligible participant from their parent or guardian. Screening assessment included documenting demographic characteristics (age, sex, height, and weight), performing a clinical history and physical examination, and obtaining blood for celiac serology (anti-endomysial and anti-transglutaminase antibodies), with clinically abnormal results leading to exclusion. Patients were also tested to define their vitamin D status (excluding those who had recently been supplemented). Participants were contacted via telephone by a research nurse one week after the baseline visit and following the review of laboratory results to confirm their participation in the study, provide instructions on taking the study product, and arrange the Week 6 and Week 12 study visits.
Participants were given the study product by the study physician (Alflorex®, produced for PrecisionBiotics Group Ltd., Cork, Ireland) containing 1 × 109 colony-forming units of Bifidobacterium longum 35624 per capsule, to be stored at room temperature and taken once each morning with a cold drink for 12 weeks. Compliance with intake was monitored by counting the remaining capsules during the study visits at Weeks 6 and 12. This was followed by a two-week washout period during which the study product was not taken. Participants were instructed to maintain their usual dietary intake and avoid foods or other supplements containing probiotics throughout the study.
The study schematic is presented in Figure 1. Participants’ IBS symptoms were measured by the study physician at baseline (one week before the intervention period), halfway through the intervention period (Week 6 of the intervention period), at the end of the intervention period (Week 12), and at follow-up (Week 14, two weeks after the intervention period, by telephone). An adapted IBS-SSS [15,16] measured five domains: abdominal pain frequency (number of days with pain), abdominal pain severity, abdominal distension severity, bowel habit satisfaction, and impact to life, on a scale of 0–10. The Wong–Baker FACES® and numeric pain rating scales [17] were used to facilitate children’s responses. Favorable changes were indicated by decreases in abdominal pain, abdominal distension, and impact to life domain scores, and by an increase in bowel habit satisfaction score. To calculate the composite IBS-SSS score, the sum of the 0–10 values for each domain was calculated and multiplied by 10. Participant diaries were provided in the local language to record parent and child perspectives on the number of IBS symptoms present during the intervention period. Questions which were suitable to be answered by both parent and child adapted from the Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS) [18] were included, relating to pain/discomfort in the upper abdomen, bowel habits, other symptoms (nausea/vomiting), and those causing restriction of activities. Stool consistency (Bristol Stool Form Scale; BSFS [19]) was recorded daily during the intervention period in the participants’ diaries. The data entered during Week 1 were treated as baseline, and weekly average stool type categories were calculated for Weeks 6 and 12 as the mean of these average daily scores.
Data were analyzed primarily using an intention-to-treat (ITT) approach, with per-protocol sensitivity analysis. Descriptive statistics were calculated for the baseline characteristics, along with the proportion of participants who experienced a clinical improvement (change of ≥50 points) in composite IBS-SSS, or a numerical improvement (change of ≥1 point) in one or more IBS-SSS domains, during the intervention period. Regional differences (between study sites) in baseline vitamin D status were analyzed using an independent t-test, and the association between baseline vitamin D status and composite IBS-SSS with linear regression. Changes from baseline in the distribution of IBS-SSS severity categories were analyzed with a generalized linear mixed model using cumulative logits. Linear mixed-effects models were constructed to analyze the changes in composite IBS-SSS, the association between IBS-SSS treatment response and baseline vitamin D status, and the mean number of QPGS reported during the study. The distributions of average stool type categories at the same timepoints were analyzed using a generalized linear mixed model using multinominal logits. For linear mixed models, missing data were handled with restricted maximum likelihood, assuming the data were missing at random. Data are presented as mean and standard deviation (±) and percentage (%) of participants. The results of the analyses for the intention to treat population are presented. Statistical significance was set at p < 0.05.

3. Results

3.1. Intention to Treat Analysis

3.1.1. Participant Characteristics

Between 1 August 2021 and 30 November 2022, 65 children/adolescents were included in the study. Of these, one was excluded due to a diagnosis of celiac disease, six dropped out before Week 6 of the study (n = 5 lost to follow-up; n = 1 unrelated adverse event: reaction to ibuprofen), and 58 completed the study and took the study product as directed (per protocol population). Baseline characteristics are presented in Table 1. In terms of vitamin D status, the majority of participants were found to be deficient (<20 ng/mL; 54.1%) or had low levels (20–30 ng/mL; 40.5%) of vitamin D. Mean vitamin D status was similar between regions (Coyhaique 17.5 ± 6.22; Santiago 20.4 ± 6.55); however, more participants from Coyhaique were deficient (77.8%) compared to Santiago (46.4%) (p = 0.35 not significant). All participants had IBS (mostly severe) with no significant correlation between IBS severity and vitamin D status (p = 0.59). Most participants had other concurrent pediatric DGBI, predominantly functional abdominal pain not otherwise specified, functional dyspepsia, and functional constipation, with a small number having non-retentive fecal incontinence. Additionally, the symptoms of bloating and nausea and the identification of a palpable bowel loop on physical examination, affected 12.5%, 1.5%, and 28.1% of participants, respectively.

3.1.2. IBS Symptom Severity

During the 12-week supplementation period, there was a significant decrease in composite IBS-SSS score from baseline (334.4 ± 76.67) to Week 6 (104.3 ± 92.36, p < 0.0001) and Week 12 (57.6 ± 71.26, p < 0.0001). The mean IBS-SSS domain scores for abdominal pain frequency, abdominal pain severity, abdominal distension severity, and impact to life significantly decreased (all p < 0.0001 for Week 6 and Week 12 versus baseline) (Figure 2). The IBS-SSS domain score for bowel habit satisfaction significantly increased (p < 0.0007 for Week 6 versus baseline; p < 0.0001 for Week 12 versus baseline) (Figure 2). A clinically significant improvement in composite IBS-SSS was experienced by 93.1% of participants at Week 6, and 96.6% at Week 12. By Week 12, numerical improvements were experienced by all (100.0%) participants in at least two IBS-SSS domains; 98.3% in at least three domains; 91.4% in at least four domains; and 56.9% in all five domains.
During the two-week follow-up between Weeks 12 and 14, there were increases in IBS-SSS composite score (+43.21, p = 0.0011), abdominal pain frequency (+0.30, p = 0.16 not significant), abdominal pain severity (+0.97, p = 0.0006), abdominal distension severity (+0.91, p = 0.0077), and impact to life (+0.35, p = 0.26 not significant), and a decrease in bowel habit satisfaction (−1.82, p = 0.0018).
The distribution of IBS severity categories changed from baseline to Week 12, with decreases in the proportion of participants with severe or moderate symptoms and increases in those with mild symptoms or in remission (p < 0.0001) (Figure 3).

3.1.3. Relationship between Baseline Vitamin D Status and IBS-SSS Treatment

There was no statistically significant correlation between baseline serum vitamin D level and the change in composite IBS-SSS score from baseline to Week 6, Week 12, or Week 14 (p = 0.79).

3.1.4. Parent and Child Perspectives of IBS Symptoms

The mean number of symptoms reported by both parent and child with the QPGS reduced from 9.6 ± 4.9 at Baseline to 6.9 ± 4.9 at Week 6 (p = 0.0005) and 6.9 ± 5.4 at Week 12 (p = 0.02).

3.1.5. Stool Consistency

There was a small numerical increase in the proportion of participants who experienced ‘normal’ (BSFS stool type 3–5) weekly average stool types, which appeared to correspond to a small decrease in those experiencing constipation and, to a lesser extent, diarrhea; however, the differences between visits were not statistically significant.

3.2. Per Protocol Sensitivity Analysis

As the six participants who were excluded from the per-protocol analysis (9.4% of the ITT population) were all early drop-outs with insufficient outcome data beyond the baseline, the results of the per-protocol sensitivity analysis were similar to the ITT results.

4. Discussion

This real-world, open-label study conducted in Chile showed significant reductions in the severity and prevalence of IBS symptoms in children and adolescents with IBS and concurrent DGBI during 12 weeks of supplementation with B. longum 35624. The findings provide evidence to support the effectiveness of this immunoregulatory probiotic strain in a vitamin D-deficient population.
This is the first study to report on the effectiveness of this specific probiotic strain in a pediatric IBS population. Few published studies from Latin America have investigated the action of other probiotic strains in children with IBS, reporting contradictory findings regarding their effects on GI symptom severity [20,21]. The clinical features of the pediatric population in this region warrant specific investigation, with a higher prevalence of childhood constipation in South America than in other countries [22], accounting for one-third of pediatric gastroenterology consultations in Chile [23]. Disease overlap between IBS and functional defecation disorders is common and has been associated with increased symptom severity and decreased quality of life [24]. In the present study, the majority of participants had other DGBI including two-thirds with functional constipation, in addition to moderate or severe IBS at baseline, yet the probiotic proved to be highly effective.
During the 12-week intervention with B. longum 35624, there were significant improvements in all IBS-SSS domain scores, including abdominal pain severity and frequency, abdominal distension severity, and bowel habit satisfaction, with a high proportion of participants experiencing improvements across multiple domains. This culminated in a clinically significant decrease in IBS-SSS composite score, and a distributional shift towards less severe IBS-SSS severity categories, reflecting the findings of published literature from adult IBS populations [11,13,25]. Although the IBS-SSS bowel habit satisfaction score improved, statistically significant changes in stool consistency were not observed. Similar findings from randomized, placebo-controlled trials of B. longum 35624 in adults with IBS have suggested that the effectiveness of this Bifidobacterium strain may be applicable to all patients with IBS, irrespective of stool pattern [11,13].
The prevalence of a broader range of GI symptoms reported by both parents and children/adolescents also improved during the study, with significantly fewer QPGS affecting participants after the probiotic intervention compared to baseline. This offers an important insight, as research has found that patient and doctor perspectives of IBS severity and its impact to life differ, which may compromise quality of life [26]. In children, IBS is known to impair physical, social, emotional, and school functioning [27] and quality of life [28], indicating the need for targeted approaches to address these aspects of well-being. In the present study, improvements in IBS symptoms were accompanied by a significant decrease in the impact of IBS to daily life, which is consistent with published real-world data demonstrating reductions in symptom severity and increased QoL in adults with IBS following a four-week intake of B. longum 35624 [25].
The observed improvements in IBS-SSS scores were evident from week six and peaked at week 12, reflecting recent real-world data trends from an adult IBS population in Russia, which showed cumulative improvements with B. longum 35624 over a 12 week period, and persistence of these effects for up to one month after probiotic intervention [29]. Conversely, randomized placebo-controlled trials have demonstrated that the positive effects of this strain on IBS symptoms were not maintained long after the cessation of intake. Similar results were observed in the present study, with statistically significant increases in IBS-SSS scores during the two-week washout period. This may suggest that this microorganism may not permanently colonize the bowel, with continuous intake required for long-term effects [11,13].
Another interesting finding of this study was the high prevalence of vitamin D deficiency in this cohort. A high prevalence of vitamin D deficiency has been reported among children in Chile, which has been attributed to the use of sunscreen, indoor activity, diet, and obesity in this region [30]. Although previous studies have shown a higher incidence of deficiency and lower serum levels of vitamin D in IBS populations, the relationship between vitamin D status and symptom severity is unclear [7]. The present study detected no correlation between baseline vitamin D status and the severity of IBS symptoms. Despite its immunoregulatory and anti-inflammatory properties and its impact on the gut microbiome, a recent meta-analysis reported significant improvements in quality of life but not symptom severity with vitamin D supplementation in people with IBS [7].
Additionally, no statistically significant correlation between baseline vitamin D status and probiotic response was detected in the present study. B. longum 35624 has been shown to bypass the inflammatory nuclear factor-kappa B pathway which typifies immune response to a pathogen, instead engaging with dendritic cells to initiate an anti-inflammatory, regulatory T-cell pathway [31]. The clinical significance of this has been demonstrated by reductions in C-reactive protein and pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in adults with inflammatory conditions [32], and restoration of a favorable IL-10:IL-12 ratio which accompanied symptom improvements in adults with IBS [11]. In this study of children and adolescents with IBS, significant improvements in GI symptoms were observed in those with adequate and low serum vitamin D levels at baseline, confirming the effectiveness of B. longum 35624 in a vitamin D deficient population. Further research is required to determine whether other probiotic strains are also effective in individuals with low vitamin D levels, and the extent to which vitamin D status influences probiotic activity in the host.
The absence of a comparator group was a key limitation of this open-label study. A notable placebo effect has been reported in IBS studies [33], with an average decrease in composite IBS-SSS score of 30 points with placebo having been reported [34]. However, the size of the reduction in composite IBS-SSS score in the current study, exceeding 270 points, the high proportion of participants who experienced a 50-point or more reduction, which has been validated as a reliable indicator of clinical improvement [15], and the consistency of these results with those of double-blind, placebo-controlled trials of B. longum 35624 in adult IBS populations [11,13] are suggestive of a true probiotic effect. Although there was a nine percent drop-out rate and missing data partly due to the impact of the 2019 coronavirus pandemic that inhibited the analysis of exploratory outcomes, the use of ITT analysis resulted in a conservative estimation of probiotic effect on the IBS symptom scores. As potential participants were identified and referred by clinicians from study sites in Santiago and Coyhaique, the study population can be considered representative of the local pediatric gastroenterology population. A randomized placebo-controlled trial with a larger sample size may be required to confirm the generalizability of the findings.

5. Conclusions

The findings of this real-world study contributed to the evidence base for the use of B. longum 35624 in the management of IBS symptoms, confirming its effectiveness in a pediatric population even in the presence of vitamin D deficiency. Future well-designed studies in a larger cohort are warranted to confirm these findings.

Author Contributions

Conceptualization, S.C.M. and S.V.P.; Methodology, S.C.M. and S.V.P.; Validation, S.C.M., S.V.P. and K.S.; Formal Analysis, S.C.M., S.V.P., L.L.M. and K.S.; Investigation, S.C.M. and S.V.P.; Resources, S.C.M., S.V.P., M.N.E.P. and J.M.M.; Data Curation, S.C.M., S.V.P., L.L.M. and K.S.; Writing—Original Draft Preparation, K.S., S.C.M. and S.V.P.; Writing—Review and Editing, K.S., S.C.M. and S.V.P.; Visualization, S.C.M., S.V.P. and K.S.; Project Administration, S.C.M.; Funding Acquisition, S.C.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research was sponsored and funded by PrecisionBiotics Group Ltd. since acquired by Novozymes A/S. Additional funding and study product was provided free of charge to the research group by Axon Pharma.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of the Institute of Nutrition and Food Technology, University of Chile (protocol code PCT 002A, approved 2 June 2021).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.

Acknowledgments

The authors thank the collaboration of Marisol Cayazzo (field nurse), Julia Abbate (secretary), and Jeannette Lara (data entry). We also appreciate the participation of the following doctors: Elías Acevedo, Bernarda Contreras, Gabriela Klapp, Jorge Saba, Mario Cuellar, Andrés Vives, Lezzy Fernández, Carlos Roa, Rossana Faundez, Paula Urrutia, and Jaime Cisneros for referring patients to us.

Conflicts of Interest

This study was sponsored by PrecisionBiotics Group Ltd. since acquired by Novozymes A/S, who manufacture the probiotic strain Bifidobacterium longum 35624TM. Additional funding and the study product was provided free of charge to the research group by Axon Pharma. Katy Sorensen is employed by Novozymes A/S. Sylvia Cruchet Muñoz, Sandra Verbeke Palma, Lydia Lera Marqués, María Nelly Espinosa Pizarro, and Jacqueline Malig Mechasqui have no conflicts of interest to declare.

References

  1. Drossman, D.A. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features, and Rome IV. Gastroenterology 2016, 150, 1262–1279. [Google Scholar] [CrossRef] [PubMed]
  2. Hyams, J.S.; Di Lorenzo, C.; Saps, M.; Shulman, R.J.; Staiano, A.; van Tilburg, M. Functional Disorders: Children and Adolescents. Gastroenterology 2016, 150, 1456–1468. [Google Scholar] [CrossRef] [PubMed]
  3. Vernon-Roberts, A.; Alexander, I.; Day, A.S. Systematic Review of Pediatric Functional Gastrointestinal Disorders (Rome IV Criteria). J. Clin Med. 2021, 10, 5087. [Google Scholar] [CrossRef] [PubMed]
  4. Velasco-Benítez, C.A.; Chanis, R.; Játiva, E.; Mejia, M.; Moreno, J.; Ramírez-Hernández, C.R.; Villamarín-Betancourt, E.A.; Gómez-Urrego, J.F. Coexistencia de trastornos gastrointestinales funcionales en lactantes y preescolares latinoamericanos. Rev. Colomb. Gastroenterol. 2019, 34, 370–375. [Google Scholar] [CrossRef]
  5. Schmulson, M.J.; Drossman, D.A. What Is New in Rome IV. J. Neurogastroenterol. Motil. 2017, 23, 151–163. [Google Scholar] [CrossRef] [PubMed]
  6. Sadeghi, A.; Biglari, M.; Nasseri Moghaddam, S. Post-infectious Irritable Bowel Syndrome: A Narrative Review. Middle East J. Dig. Dis. 2019, 11, 69–75. [Google Scholar] [CrossRef] [PubMed]
  7. Bin, Y.; Kang, L.; Lili, Y. Vitamin D status in irritable bowel syndrome and the impact of supplementation on symptoms: A systematic review and meta-analysis. Nutr. Hosp. 2022, 39, 1144–1152. [Google Scholar] [PubMed]
  8. Quigley, E.M.; Fried, M.; Gwee, K.A.; Khalif, I.; Hungin, A.P.; Lindberg, G.; Abbas, Z.; Fernandez, L.B.; Bhatia, S.J.; Schmulson, M.; et al. World Gastroenterology Organisation Global Guidelines Irritable Bowel Syndrome: A Global Perspective Update September 2015. J. Clin. Gastroenterol. 2016, 50, 704–713. [Google Scholar] [CrossRef] [PubMed]
  9. Hill, C.; Guarner, F.; Reid, G.; Gibson, G.R.; Merenstein, D.J.; Pot, B.; Morelli, L.; Canani, R.B.; Flint, H.J.; Salminen, S.; et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014, 11, 506–514. [Google Scholar] [CrossRef] [PubMed]
  10. Cruchet, S.; Furnes, R.; Maruy, A.; Hebel, E.; Palacios, J.; Medina, F.; Ramirez, N.; Orsi, M.; Rondon, L.; Sdepanian, V.; et al. The use of probiotics in pediatric gastroenterology: A review of the literature and recommendations by Latin-American experts. Paediatr. Drugs 2015, 17, 199–216. [Google Scholar] [CrossRef] [PubMed]
  11. O’Mahony, L.; McCarthy, J.; Kelly, P.; Hurley, G.; Luo, F.; Chen, K.; O’sullivan, G.C.; Kiely, B.; Collins, J.K.; Shanahan, F.; et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles. Gastroenterology 2005, 128, 541–551. [Google Scholar] [CrossRef] [PubMed]
  12. Lyseng-Williamson, K. Bifidobacterium infantis 35624 as a probiotic dietary supplement: A profile of its use. Drugs Ther. Perspect. 2017, 33, 368–374. [Google Scholar] [CrossRef]
  13. Whorwell, P.J.; Altringer, L.; Morel, J.; Bond, Y.; Charbonneau, D.; O’Mahony, L.; Kiely, B.; Shanahan, F.; Quigley, E.M.M. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am. J. Gastroenterol. 2006, 101, 1581–1590. [Google Scholar] [CrossRef] [PubMed]
  14. Hoy-Schulz, Y.E.; Jannat, K.; Roberts, T.; Zaidi, S.H.; Unicomb, L.; Luby, S.; Parsonnet, J. Safety and acceptability of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 in Bangladeshi infants: A phase I randomized clinical trial. BMC Complement. Altern. Med. 2016, 16, 44. [Google Scholar] [CrossRef] [PubMed]
  15. Francis, C.Y.; Morris, J.; Whorwell, P.J. The irritable bowel severity scoring system: A simple method of monitoring irritable bowel syndrome and its progress. Aliment. Pharmacol. Ther. 1997, 11, 395–402. [Google Scholar] [CrossRef] [PubMed]
  16. Almansa, C.; García-Sánchez, R.; Barceló, M.; Díaz-Rubio, M.; Rey, E. Translation, cultural adaptation and validation of a Spanish version of the Irritable Bowel Syndrome Severity Score. Rev. Esp. Enferm. Dig. 2011, 103, 612–618. [Google Scholar] [CrossRef] [PubMed]
  17. Baker, C.M.; Wong, D.L. QUEST: A process of pain assessment in children (continuing education credit). Orthop. Nurs. 1987, 6, 11–21. [Google Scholar] [CrossRef] [PubMed]
  18. Ruiz Díaz, M.A.; Suárez Parga, J.M.; Pardo Merino, A.; García Vargas, M.; Pascual Renedo, V. Adaptación cultural al español y validación de la escala GSFQ (Gastrointestinal Short Form Questionnaire). Gastroenterol. Y Hepatol. 2009, 32, 9–21. [Google Scholar] [CrossRef] [PubMed]
  19. Mínguez Pérez, M.; Benages Martínez, A. The Bristol scale-A useful system to assess stool form? Rev. Esp. Enferm. Dig. 2009, 101, 305–311. [Google Scholar] [PubMed]
  20. Vázquez-Frias, R.; Consuelo-Sánchez, A.; Acosta-Rodríguez-Bueno, C.P.; Blanco-Montero, A.; Robles, D.C.; Cohen, V.; Márquez, D.; Perez, M. Efficacy and Safety of the Adjuvant Use of Probiotic Bacillus clausii Strains in Pediatric Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study. Paediatr. Drugs. 2023, 25, 115–126. [Google Scholar] [CrossRef] [PubMed]
  21. Barraza-Ortiz, D.A.; Pérez-López, N.; Medina-López, V.M.; Minero-Alfaro, J.I.; Zamarripa-Dorsey, F.; Fernández-Martínez, N.d.C.; Llorente-Ramón, A.; Ramos-Aguilar, G.A. Combination of a Probiotic and an Antispasmodic Increases Quality of Life and Reduces Symptoms in Patients with Irritable Bowel Syndrome: A Pilot Study. Dig. Dis. 2021, 39, 294–300. [Google Scholar] [CrossRef] [PubMed]
  22. Rajindrajith, S.; Devanarayana, N.M.; Crispus Perera, B.J.; Benninga, M.A. Childhood constipation as an emerging public health problem. World J. Gastroenterol. 2016, 22, 6864–6875. [Google Scholar] [CrossRef]
  23. Guiraldes, E. Pediatric Gastroenterology in Chile—A Personal Perspective. J. Pediatr. Gastroenterol. Nutr. 2001, 33, 231–232. [Google Scholar] [PubMed]
  24. Kaplan, A.I.; Mazor, Y.; Prott, G.M.; Sequeira, C.; Jones, M.P.; Malcolm, A. Experiencing multiple concurrent functional gastrointestinal disorders is associated with greater symptom severity and worse quality of life in chronic constipation and defecation disorders. Neurogastroenterol. Motil. 2023, 35, e14524. [Google Scholar] [CrossRef] [PubMed]
  25. Sabaté, J.M.; Iglicki, F. Effect of Bifidobacterium longum 35624 on disease severity and quality of life in patients with irritable bowel syndrome. World J. Gastroenterol. 2022, 28, 732–744. [Google Scholar] [CrossRef] [PubMed]
  26. Hulme, K.; Chilcot, J.; Smith, M.A. Doctor-patient relationship and quality of life in Irritable Bowel Syndrome: An exploratory study of the potential mediating role of illness perceptions and acceptance. Psychol. Health Med. 2018, 23, 674–684. [Google Scholar] [CrossRef] [PubMed]
  27. Varni, J.W.; Lane, M.M.; Burwinkle, T.M.; Fontaine, E.N.; Youssef, N.N.; Schwimmer, J.B.; Pardee, P.E.; Pohl, J.F.; Easley, D.J. Health-related quality of life in pediatric patients with irritable bowel syndrome: A comparative analysis. J. Dev. Behav. Pediatr. 2006, 27, 451–458. [Google Scholar] [CrossRef] [PubMed]
  28. Cassar, G.E.; Youssef, G.J.; Knowles, S.; Moulding, R.; Austin, D.W. Health-Related Quality of Life in Irritable Bowel Syndrome: A Systematic Review and Meta-analysis. Gastroenterol. Nurs. 2020, 43, E102–E122. [Google Scholar] [CrossRef] [PubMed]
  29. Solovyeva, O.; Nekrasova, A.; Topalova, I.; Ponomarenko, V.A.; Tsurtsumiia, D.B.; Ilyashevich, I.G. Long-term probiotic administration for irritable bowel syndrome: A legal need. Ter. Arkhiv. 2023, 95, 7. [Google Scholar] [CrossRef] [PubMed]
  30. Pérez-Bravo, F.; Duarte, L.; Arredondo-Olguín, M.; Iñiguez, G.; Castillo-Valenzuela, O. Vitamin D status and obesity in children from Chile. Eur. J. Clin. Nutr. 2022, 76, 899–901. [Google Scholar] [CrossRef]
  31. Giron, F.; Quigley, E.M.M. Pharmabiotic Manipulation of the Microbiota in Gastrointestinal Disorders: A Clinical Perspective. J. Neurogastroenterol. Motil. 2018, 24, 355–366. [Google Scholar] [CrossRef] [PubMed]
  32. Groeger, D.; O’Mahony, L.; Murphy, E.F.; Bourke, J.F.; Dinan, T.G.; Kiely, B.; Shanahan, F.; Quigley, E.M. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes 2013, 4, 325–339. [Google Scholar] [CrossRef] [PubMed]
  33. Weerts, Z.; Vork, L.; Mujagic, Z.; Keszthelyi, D.; Hesselink, M.A.M.; Kruimel, J.; Leue, C.; Muris, J.W.; Jonkers, D.M.A.E.; Masclee, A.A.M. Reduction in IBS symptom severity is not paralleled by improvement in quality of life in patients with irritable bowel syndrome. Neurogastroenterol. Motil. 2019, 31, e13629. [Google Scholar] [CrossRef] [PubMed]
  34. Martoni, C.J.; Srivastava, S.; Leyer, G.J. Lactobacillus acidophilus DDS-1 and Bifidobacterium lactis UABla-12 Improve Abdominal Pain Severity and Symptomology in Irritable Bowel Syndrome: Randomized Controlled Trial. Nutrients 2020, 12, 363. [Google Scholar] [CrossRef] [PubMed]
Nutrients 16 01967 g001
Figure 1. Schematic diagram of study design.
Figure 1. Schematic diagram of study design.
Nutrients 16 01967 g001
Nutrients 16 01967 g002
Figure 2. Adapted IBS-SSS domain scores during the probiotic supplementation period. IBS-SSS: irritable bowel syndrome severity scoring system; ±: standard deviation; AP-F: abdominal pain frequency; AP-S: abdominal pain severity; AD-S: abdominal distension severity; BH-S: bowel habit satisfaction; ITL: impact to life. Week 6 all p < 0.0001 versus baseline except BH-S (p < 0.0007); Week 12 all p < 0.0001.
Figure 2. Adapted IBS-SSS domain scores during the probiotic supplementation period. IBS-SSS: irritable bowel syndrome severity scoring system; ±: standard deviation; AP-F: abdominal pain frequency; AP-S: abdominal pain severity; AD-S: abdominal distension severity; BH-S: bowel habit satisfaction; ITL: impact to life. Week 6 all p < 0.0001 versus baseline except BH-S (p < 0.0007); Week 12 all p < 0.0001.
Nutrients 16 01967 g002
Nutrients 16 01967 g003
Figure 3. IBS-SSS severity category by timepoint (percentage of participants). IBS-SSS: irritable bowel syndrome severity scoring system.
Figure 3. IBS-SSS severity category by timepoint (percentage of participants). IBS-SSS: irritable bowel syndrome severity scoring system.
Nutrients 16 01967 g003
Table 1. Baseline characteristics of participants.
Table 1. Baseline characteristics of participants.
Characteristicn = 64
Demographics
Female, n (%) 42 (65.6)
Age (years), mean ± SD12.3 ± 2.9
Resident of Santiago, n (%)47 (73.4)
Resident of Coyhaique, n (%)17 (26.6)
Anthropometrics, mean ± SD
Weight (kg)45.7 ± 15.3
Height (cm)148.1 ± 15.1
BMI (kg/m2)20.3 ± 4.0
Biochemistry, mean ± SD
Serum vitamin D *, ng/mL (sufficiency ≥ 30 ng/mL)19.7 ± 6.50
Concurrent pediatric DGBI (Rome IV criteria [5]), n (%)
H2. Functional abdominal pain disorders64 (100.0)
H2a. Functional dyspepsia45 (70.3)
H2b. Irritable bowel syndrome (IBS)64 (100.0)
H2c. Abdominal migraine0 (0.0)
H2d. Functional abdominal pain not otherwise specified60 (93.8)
H3. Functional defecation disorders60 (93.8)
H3a. Functional constipation43 (67.2)
H3b. Non-retentive fecal incontinence9 (14.1)
Functional defecation disorder not otherwise specified8 (12.5)
IBS severity
Participants in IBS remission (IBS-SSS < 75), n (%)0 (0.0)
Participants with mild IBS (IBS-SSS 75–175), n (%)2 (3.1)
Participants with moderate IBS (IBS-SSS 176–300), n (%)19 (29.7)
Participants with severe IBS (IBS-SSS > 300), n (%)43 (67.2)
±SD: standard deviation; BMI: body mass index; DGBI: disorders of gut–brain interaction; IBS-SSS: irritable bowel syndrome severity scoring system. * n = 37.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Cruchet Muñoz, S.; Verbeke Palma, S.; Lera Marqués, L.; Espinosa Pizarro, M.N.; Malig Mechasqui, J.; Sorensen, K. Effects of Bifidobacterium longum 35624 in Children and Adolescents with Irritable Bowel Syndrome. Nutrients 2024, 16, 1967. https://doi.org/10.3390/nu16121967

AMA Style

Cruchet Muñoz S, Verbeke Palma S, Lera Marqués L, Espinosa Pizarro MN, Malig Mechasqui J, Sorensen K. Effects of Bifidobacterium longum 35624 in Children and Adolescents with Irritable Bowel Syndrome. Nutrients. 2024; 16(12):1967. https://doi.org/10.3390/nu16121967

Chicago/Turabian Style

Cruchet Muñoz, Sylvia, Sandra Verbeke Palma, Lydia Lera Marqués, María Nelly Espinosa Pizarro, Jacqueline Malig Mechasqui, and Katy Sorensen. 2024. "Effects of Bifidobacterium longum 35624 in Children and Adolescents with Irritable Bowel Syndrome" Nutrients 16, no. 12: 1967. https://doi.org/10.3390/nu16121967

APA Style

Cruchet Muñoz, S., Verbeke Palma, S., Lera Marqués, L., Espinosa Pizarro, M. N., Malig Mechasqui, J., & Sorensen, K. (2024). Effects of Bifidobacterium longum 35624 in Children and Adolescents with Irritable Bowel Syndrome. Nutrients, 16(12), 1967. https://doi.org/10.3390/nu16121967

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop