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Barnett D, Thijs C, Mommers M, Endika M, Klostermann C, Schols H, Smidt H, Nauta A, Arts I, Penders J. Why do babies cry? Exploring the role of the gut microbiota in infantile colic, constipation, and cramps in the KOALA birth cohort study. Gut Microbes 2025; 17:2485326. [PMID: 40159147 PMCID: PMC11959906 DOI: 10.1080/19490976.2025.2485326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 02/17/2025] [Accepted: 03/18/2025] [Indexed: 04/02/2025] Open
Abstract
Gastrointestinal symptoms are common during infancy, including infantile colic. Colic can be loosely defined as prolonged and recurrent crying without obvious cause. The cause indeed remains unclear despite much research. Results on infant nutrition are inconclusive, but prior work has linked maternal mental health to infant crying. Recently, several small studies have described associations between gut microbiota and colic. We used a larger cohort to examine the role of the microbiota in infant gastrointestinal health, while also accounting for other biopsychosocial factors. Using fecal 16S rRNA gene amplicon sequencing data from 1,012 infants in the KOALA birth cohort, we examined associations between the 1-month gut microbiota and parent-reported functional gastrointestinal symptoms throughout infancy, including colic, constipation, and cramps. These analyses were adjusted for biopsychosocial factors that were associated with symptoms in a broader analysis involving 2,665 participants. In 257 infants, we also explored associations between breastmilk human milk oligosaccharides (HMOs) and gastrointestinal symptoms. Higher relative abundance of Staphylococcus at one month was associated with less constipation in the first three months of life. Conversely, Ruminococcus gnavus group abundance was associated with more colicky symptoms, particularly between four and seven months. Breastmilk concentrations of the HMOs lacto-N-hexaose (LNH) and lacto-N-neohexaose (LNnH) were associated with less constipation in the first three months. Our results support the conclusion that gut microbiota are relevant in infantile colic and constipation. However more work is needed to elucidate the underlying mechanisms, and explore their interplay with other relevant biopsychosocial factors such as maternal mental health.
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Affiliation(s)
- David Barnett
- Maastricht Centre for Systems Biology, Maastricht University, Maastricht, Netherlands
- NUTRIM School for Nutrition and Translational Research in Metabolism, Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Carel Thijs
- CAPHRI Care and Public Health Research Institute, Department of Epidemiology, Maastricht University, Maastricht, Netherlands
| | - Monique Mommers
- CAPHRI Care and Public Health Research Institute, Department of Epidemiology, Maastricht University, Maastricht, Netherlands
| | - Martha Endika
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands
| | - Cynthia Klostermann
- Department of Food Chemistry, Wageningen University & Research, Wageningen, Netherlands
| | - Henk Schols
- Department of Food Chemistry, Wageningen University & Research, Wageningen, Netherlands
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands
| | - Arjen Nauta
- FrieslandCampina Ingredients, FrieslandCampina, Amersfoort, Netherlands
| | - Ilja Arts
- Maastricht Centre for Systems Biology, Maastricht University, Maastricht, Netherlands
| | - John Penders
- NUTRIM School for Nutrition and Translational Research in Metabolism, Department of Medical Microbiology, Infectious Diseases and Infection Prevention, Maastricht University Medical Center+, Maastricht, Netherlands
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Gong S, Yu Z, Ding Y, Wang Y, Li X, Gu S. Characteristics of functional constipation and analysis of intestinal microbiota in children aged 0-4 in Zunyi region. BMC Pediatr 2025; 25:45. [PMID: 39825285 PMCID: PMC11748605 DOI: 10.1186/s12887-024-05383-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 12/30/2024] [Indexed: 01/20/2025] Open
Abstract
BACKGROUND Functional constipation (FC) significantly impacts children's health. This study investigates the prevalence and microbiota characteristics of FC in children aged 0-4 years in Zunyi area. METHODS From October to December 2023, 2039 children aged 0-4 years in Zunyi were selected using stratified sampling and cross-sectional survey methods. A questionnaire based on Rome IV diagnostic criteria was used. Twenty-nine children with FC were randomly selected as the functional constipation group (FCG), and 26 healthy children, matched for age, sex, and area, were selected as the control group (CG). RESULTS A total of 2051 questionnaires were collected, with 2039 valid responses. Among them, 151 children had FC, resulting in a prevalence rate of 7.4%. The prevalence rates in boys and girls were 6.6% and 8.5%, respectively, with no significant gender difference (P > 0.05). Alpha diversity analysis revealed higher richness and diversity of intestinal flora in the FCG compared to the CG. At the phylum level, Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes were dominant in both groups. The FCG showed a higher relative abundance of Firmicutes, Actinobacteria, and Proteobacteria compared to the CG (P < 0.05). CONCLUSIONS The prevalence of FC in children aged 0-4 years in Zunyi is 7.4%. Disease characteristics vary with age and living environment but are unrelated to gender. The gut microbiota of children with FC shows significant alterations, with higher diversity and specific phyla abundance.
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Affiliation(s)
- Shungang Gong
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Zhengbo Yu
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Yuan Ding
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Yue Wang
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Xi Li
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China
| | - Shengli Gu
- Department of Pediatric Surgery, The Third Affiliated Hospital of Zunyi Medical University, The First People's Hospital of Zunyi, No. 98, Feng Huang Road, Huichuan District, Zunyi, Guizhou, 563000, China.
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Di Stefano M. Fecal Microbiota Transplantation in the Treatment of Severe Constipation in Children: Is It the Future? Am J Gastroenterol 2024; 119:2187-2188. [PMID: 39150086 DOI: 10.14309/ajg.0000000000002985] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 07/22/2024] [Indexed: 08/17/2024]
Affiliation(s)
- Michele Di Stefano
- 1st Internal Medicine Unit, Department of Medicine, IRCCS "S.Matteo" Hospital Foundation, Pavia, Italy
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Yang WC, Zeng BS, Liang CS, Hsu CW, Su KP, Wu YC, Tu YK, Lin PY, Stubbs B, Chen TY, Chen YW, Shiue YL, Zeng BY, Suen MW, Hung CM, Wu MK, Tseng PT. Efficacy and acceptability of different probiotic products plus laxatives for pediatric functional constipation: a network meta-analysis of randomized controlled trials. Eur J Pediatr 2024; 183:3531-3541. [PMID: 38806862 PMCID: PMC11263257 DOI: 10.1007/s00431-024-05568-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 04/06/2024] [Accepted: 04/09/2024] [Indexed: 05/30/2024]
Abstract
The prevalence of pediatric constipation ranges from 0.7 to 29.6% across different countries. Functional constipation accounts for 95% of pediatric constipation, and the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. We aimed to compare the efficacy and acceptability of different probiotic supplements for pediatric functional constipation. The current frequentist model-based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children. The primary outcome was changes in bowel movement or stool frequency; acceptability outcome was all-cause discontinuation. Nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls). Most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments (SMD = 1.37, 95% CI: 0.32 to 2.43). All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments. Conclusion: The results of our NMA support the application of an advanced combination of probiotics and laxatives for pediatric functional constipation if there is no concurrent contraindication. Registration: PROSPERO (CRD42022298724). What is Known: • Despite of the high prevalence of pediatric constipation, which ranges from 0.7% to 29.6%, the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. The widely heterogeneous strains of probiotics let the traditional meta-analysis, which pooled all different strains into one group, be nonsense and insignificant. What is New: • By conducting a comprehensive network meta-analysis, we aimed to compare the efficacy and acceptability of different strains of probiotic supplements for pediatric functional constipation. Network meta-analysis of nine randomized controlled trials revealed that the most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives was associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments. All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.
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Affiliation(s)
- Wei-Chieh Yang
- Department of Pediatrics, Ping An Medical Clinic, Tainan, Taiwan
| | - Bing-Syuan Zeng
- Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Sung Liang
- Department of Psychiatry, Beitou Branch, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Wei Hsu
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuan-Pin Su
- Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan
- College of Medicine, China Medical University, Taichung, Taiwan
- An-Nan Hospital, China Medical University, Tainan, Taiwan
| | - Yi-Cheng Wu
- Department of Sports Medicine, Landseed International Hospital, Taoyuan, Taiwan
| | - Yu-Kang Tu
- Institute of Health Data Analytics & Statistics, College of Public Health, National Taiwan University, Taipei, Taiwan
- Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
| | - Pao-Yen Lin
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Institute for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Brendon Stubbs
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK
- Positive Ageing Research Institute (PARI), Faculty of Health, Social Care Medicine and Education, Anglia Ruskin University, Chelmsford, UK
| | - Tien-Yu Chen
- Department of Psychiatry, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei, Taiwan
- Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan
| | - Yen-Wen Chen
- Prospect Clinic for Otorhinolaryngology & Neurology, No. 252, Nanzixin Road, Nanzi District, Kaohsiung City, 81166, Taiwan
| | - Yow-Ling Shiue
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
- Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Bing-Yan Zeng
- Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Mein-Woei Suen
- Department of Psychology, College of Medical and Health Science, Asia University, 500, Lioufeng Rd., Wufeng, Taichung, 41354, Taiwan.
- Gender Equality Education and Research Center, Asia University, Taichung, Taiwan.
- Department of Medical Research, Asia University Hospital, Asia University, Taichung, Taiwan.
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
| | - Chao-Ming Hung
- Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.
- School of Medicine, College of Medicine, I-Shou University, No. 1, Sec. 1, Xuecheng Rd., Dashu Dist., Kaohsiung City, 840301, Taiwan.
| | - Ming-Kung Wu
- Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
| | - Ping-Tao Tseng
- Department of Psychology, College of Medical and Health Science, Asia University, 500, Lioufeng Rd., Wufeng, Taichung, 41354, Taiwan.
- Prospect Clinic for Otorhinolaryngology & Neurology, No. 252, Nanzixin Road, Nanzi District, Kaohsiung City, 81166, Taiwan.
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
- Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan.
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Noruzpour A, Gholam-Mostafaei FS, Looha MA, Dabiri H, Ahmadipour S, Rouhani P, Ciacci C, Rostami-Nejad M. Assessment of salivary microbiota profile as a potential diagnostic tool for pediatric celiac disease. Sci Rep 2024; 14:16712. [PMID: 39030381 PMCID: PMC11271620 DOI: 10.1038/s41598-024-67677-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 07/15/2024] [Indexed: 07/21/2024] Open
Abstract
The association between oral dysbiosis and celiac disease (CD) remains poorly understood, as does the impact of CD-associated dysbiosis on disease development or exacerbation. This study aims to investigate alterations in salivary microbial composition among children with CD. In this cross-sectional study, saliva samples from 12 children with active CD (A-CD group), 14 children with CD on a gluten-free diet (GFD), and 10 healthy control (HC) children were analyzed using DNA sequencing targeting the 16S ribosomal RNA. Both patients in A-CD and GFD groups showed a significant increase (p = 0.0001) in the Bacteroidetes phylum, while the Actinobacteria phylum showed a significant decrease (p = 0.0001). Notably, the Rothia genus and R.aeria also demonstrated a significant decrease (p = 0.0001) within the both CD groups as compare to HC. Additionally, the control group displayed a significant increase (p = 0.006) in R.mucilaginosa species compared to both CD patient groups. Distinct bacterial strains were abundant in the saliva of patients with active CD, indicating a unique composition of the salivary microbiome in individuals with CD. These findings suggest that our approach to assessing salivary microbiota changes may contribute to developing noninvasive methods for diagnosing and treating CD.
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Affiliation(s)
- Asal Noruzpour
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medial Science, Tehran, Iran
| | - Fahimeh Sadat Gholam-Mostafaei
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Azizmohammad Looha
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Dabiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medial Science, Tehran, Iran
| | - Shokoufeh Ahmadipour
- Pediatric Gastroenterologist, Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Pejman Rouhani
- Department of Pediatric Gastroenterology and Hepatology, Mofid Children's Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Carolina Ciacci
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - Mohammad Rostami-Nejad
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Kwiatkowska M, Gołębiewski M, Sikora M, Rycharska EŁ, Krogulska A. The oral cavity and intestinal microbiome in children with functional constipation. Sci Rep 2024; 14:8283. [PMID: 38594374 PMCID: PMC11004141 DOI: 10.1038/s41598-024-58642-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2023] [Accepted: 04/01/2024] [Indexed: 04/11/2024] Open
Abstract
Constipation is a widespread problem in paediatric practice, affecting almost 30% of children. One of the key causal factors of constipation may be disturbances in the homeostasis of the gastrointestinal microbiome. The aim of the study was to determine whether the oral and fecal microbiomes differ between children with and without constipation. A total of 91 children over three years of age were included in the study. Of these, 57 were qualified to a group with constipation, and 34 to a group without. The saliva and stool microbiomes were evaluated using 16S rRNA gene amplicon sequencing. Functional constipation was associated with characteristic bacterial taxa in the fecal microbiota. Statistically significant differences were found at the family level: Burkholderiaceae (q = 0.047), Christensenellaceae (q = 0.047), Chlostridiaceae (q = 0.047) were significantly less abundant in the constipation group, while the Tannerellaceae (q = 0.007) were more abundant. At the genus level, the significant differences were observed for rare genera, including Christensenellaceae r-7 (q = 2.88 × 10-2), Fusicatenibacter (q = 2.88 × 10-2), Parabacteroides (q = 1.63 × 10-2), Romboutsia (q = 3.19 × 10-2) and Subdoligranulum (q = 1.17 × 10-2). All of them were less abundant in children with constipation. With the exception of significant taxonomic changes affecting only feces, no differences were found in the alpha and beta diversity of feces and saliva. Children with functional constipation demonstrated significant differences in the abundance of specific bacteria in the stool microbiome compared to healthy children. It is possible that the rare genera identified in our study which were less abundant in the constipated patients (Christensellaceae r-7, Fusicatenibacter, Parabacteroides, Romboutsia and Subdoligranulum) may play a role in protection against constipation. No significant differences were observed between the two groups with regard to the saliva microbiome.
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Affiliation(s)
- Monika Kwiatkowska
- Department of Paediatrics, Allergology and Gastroenterology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100, Torun, Poland.
- , Bydgoszcz, Poland.
| | - Marcin Gołębiewski
- Department of Plant Physiology and Biotechnology, Nicolaus Copernicus University, 87-100, Torun, Poland
- Interdisciplinary Centre of Modern Technologies, Nicolaus Copernicus University, 87-100, Torun, Poland
| | - Marcin Sikora
- Interdisciplinary Centre of Modern Technologies, Nicolaus Copernicus University, 87-100, Torun, Poland
| | - Ewa Łoś Rycharska
- Department of Paediatrics, Allergology and Gastroenterology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100, Torun, Poland
| | - Aneta Krogulska
- Department of Paediatrics, Allergology and Gastroenterology, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, 87-100, Torun, Poland
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Fedele F, Fioretti MT, Scarpato E, Martinelli M, Strisciuglio C, Miele E. The ten "hard" questions in pediatric functional constipation. Ital J Pediatr 2024; 50:64. [PMID: 38649896 PMCID: PMC11036569 DOI: 10.1186/s13052-024-01623-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Accepted: 02/25/2024] [Indexed: 04/25/2024] Open
Abstract
Functional constipation is a common problem in childhood and has a great impact on social, physical, and emotional functioning of affected children and their caregivers. No organic cause of the constipation can be found in approximately 95% of children, defining the "so-called" chronic functional constipation. Its prevalence has been reported to range from 0.7 to 29.6%, with a median of 12%. The diagnosis of functional constipation is exclusively clinical based on the pediatric diagnostic Rome criteria for functional gastrointestinal disorders and does not routinely require laboratory and/or radiological investigations. In case of alarm signs and symptoms that may suggest organic diseases, further investigations can be required. The therapeutic management is based on non-pharmacological and pharmacological approaches. Education, demystification of constipation and reward-based toilet training represent the cornerstones of nonpharmacological management. Disimpaction, maintenance treatment and weaning of medication are all elements of pharmacological treatment. Osmotic laxatives, mainly polyethylene glycol (PEG), are considered the first-choice laxative for both disimpaction and maintenance treatment. The aim of this review is to provide pediatric gastroenterologists with a practical tool to support the clinical and therapeutic management of children and adolescents affected by chronic functional constipation.
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Affiliation(s)
- Flora Fedele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Maria Teresa Fioretti
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Elena Scarpato
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Massimo Martinelli
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.
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Cai R, Zhou C, Tang R, Meng Y, Zeng J, Li Y, Wen X. Current insights on gut microbiome and chronic urticaria: progress in the pathogenesis and opportunities for novel therapeutic approaches. Gut Microbes 2024; 16:2382774. [PMID: 39078229 PMCID: PMC11290762 DOI: 10.1080/19490976.2024.2382774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 07/12/2024] [Accepted: 07/17/2024] [Indexed: 07/31/2024] Open
Abstract
Chronic urticaria (CU) is a prevalent skin disorder greatly impacting the patients' life quality, in which immune dysregulation mediated by gut microbiome plays a significant role. Several studies have found the gut dysbiosis exists in patients with CU. In addition, infection may also be one of the causes of CU. The primary treatment currently used for CU is the second-generation non-sedating H1-antihistamines (nsAH). However, there are some limitations in current therapies. Based on the latest evidence, this review provides an updated overview of how the gut dysbiosis influences CU development, explores potential therapeutic approaches based on the gut microbiota and summarizes the interaction between gut microbiota and current treatment.
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Affiliation(s)
- Rui Cai
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Changhan Zhou
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Ruisi Tang
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yuanling Meng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Jumei Zeng
- West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yuqing Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Xiang Wen
- Department of Dermatology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Motoki N, Inaba Y, Toubou H, Hasegawa K, Shibazaki T, Tsukahara T, Nomiyama T. Impact of breastfeeding during infancy on functional constipation at 3 years of age: the Japan Environment and Children's Study. Int Breastfeed J 2023; 18:57. [PMID: 37926840 PMCID: PMC10626743 DOI: 10.1186/s13006-023-00592-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 10/13/2023] [Indexed: 11/07/2023] Open
Abstract
BACKGROUND There is a lack of large, nationwide, birth cohort studies in Japan that examine the relationships of initial feeding habits and breastfeeding period duration with offspring functional constipation at 3 years of age. This study assessed the impact of breastfeeding during infancy on early childhood functional constipation. METHODS The fixed data of 70,078 singleton births from the ongoing Japan Environment and Children's Study cohort study that commenced in 2011 were used to identify functional constipation as estimated by Rome III at 3 years of age. The exposure variables were breastfeeding period duration until 12 months of age (never, up to 6 months, or ≥ 7 months) as well as breastfeeding status at 1 month and 6 months of age (breastfeeding exclusively, partial breastfeeding, or infant formula feeding only). Multiple logistic regression analysis was employed to search for correlations for functional constipation development with breastfeeding period duration until 12 months of age and breastfeeding status during infancy. RESULTS We identified 8,118 toddlers (11.6%) who met the Rome III criteria at 3 years of age. After controlling for potential covariates, a breastfeeding period duration of 7 months or more was inversely related to functional constipation development (≥ 7 months: adjusted odds ratio [OR] [95% confidence interval (CI)] 0.76 [0.65, 0.88] versus never breastfed, P for trend < 0.001). Other initial feeding methods were significantly related to an increased risk of functional constipation as compared with breastfeeding exclusively at 1 month of age (partial breastfeeding: adjusted OR [95% CI] 1.17 [1.11, 1.23], formula feeding only: 1.23 [1.07, 1.40]) and 6 months of age (partial breastfeeding: adjusted OR [95% CI] 1.18 [1.12, 1.24], formula feeding only: adjusted OR [95% CI] 1.42 [1.20, 1.68]). CONCLUSION This large nationwide survey revealed a possible protective effect of a prolonged breastfeeding period duration and early exclusive breastfeeding in infancy on functional constipation at 3 years.
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Affiliation(s)
- Noriko Motoki
- Center for Perinatal, Pediatric, and Environmental Epidemiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
| | - Yuji Inaba
- Center for Perinatal, Pediatric, and Environmental Epidemiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
- Department of Neurology, Nagano Children's Hospital, Azumino, Nagano, Japan
- Life Science Research Center, Nagano Children's Hospital, Azumino, Nagano, Japan
| | - Hirokazu Toubou
- Department of Preventive Medicine and Public Health, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Kohei Hasegawa
- Department of Preventive Medicine and Public Health, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Takumi Shibazaki
- Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Teruomi Tsukahara
- Center for Perinatal, Pediatric, and Environmental Epidemiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
- Department of Preventive Medicine and Public Health, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
| | - Tetsuo Nomiyama
- Center for Perinatal, Pediatric, and Environmental Epidemiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan
- Department of Preventive Medicine and Public Health, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
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10
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Wan M, King L, Baugh N, Arslan Z, Snauwaert E, Paglialonga F, Shroff R. Gutted: constipation in children with chronic kidney disease and on dialysis. Pediatr Nephrol 2023; 38:3581-3596. [PMID: 36622442 PMCID: PMC10514126 DOI: 10.1007/s00467-022-05849-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/13/2022] [Accepted: 12/01/2022] [Indexed: 01/10/2023]
Abstract
Functional constipation is a common problem in otherwise healthy children. Children with chronic kidney disease (CKD) and on dialysis have additional disease-related risk factors including the uremic milieu, fluid and dietary restrictions, and decreased physical activity, as well as treatment-related risk factors such as dialysis therapy and polypharmacy that contribute to and compound the problem. Constipation causes significant distress for children and their caregivers. In children on peritoneal dialysis, severe constipation can impede catheter function and ultrafiltration. Accumulating evidence points to a possible bidirectional relationship between constipation and CKD, potentially mediated by gut dysbiosis with consequent increased generation of gut-derived uremic toxins and disruption of intestinal epithelium integrity leading to translocation of noxious luminal contents into the circulation inducing systemic inflammation. Effective management of constipation is required but there is little published data on the safety and effectiveness of treatments in adults or children with CKD. In this review, we discuss the diagnosis and epidemiology of functional constipation, provide an overview of its pathophysiology, summarize the therapeutic management, and reflect on the challenges in children with CKD.
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Affiliation(s)
- Mandy Wan
- Evelina Pharmacy Department, Evelina London Children's Hospital, NHS Foundation Trust, Guy's and St ThomasWestminster Bridge Road, London, SE1 7EH, UK.
- Institute of Pharmaceutical Science, King's College London, London, UK.
| | - Lillian King
- UCL Great Ormond Street Hospital for Children and Institute of Child Health, London, UK
| | - Natasha Baugh
- UCL Great Ormond Street Hospital for Children and Institute of Child Health, London, UK
| | - Zainab Arslan
- UCL Great Ormond Street Hospital for Children and Institute of Child Health, London, UK
| | | | - Fabio Paglialonga
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Rukshana Shroff
- UCL Great Ormond Street Hospital for Children and Institute of Child Health, London, UK
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11
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Yuan Y, Lu Y, Zhang Z, Cheng W, Yan K, Zheng Y, Jin Y, Liu Z. Characteristics of the Cajal interstitial cells and intestinal microbiota in children with refractory constipation. Microb Pathog 2023; 184:106373. [PMID: 37769855 DOI: 10.1016/j.micpath.2023.106373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 09/21/2023] [Accepted: 09/22/2023] [Indexed: 10/03/2023]
Abstract
BACKGROUND Children with refractory constipation experience intense and persistent symptoms that greatly diminish their quality of life. However, the underlying pathophysiological mechanism responsible for this condition remains uncertain. Our objective was to evaluate characteristics of colonic motor patterns and interstitial cells of Cajal (ICCs) to refractory constipation children, as well as intestinal microbiota compositions. METHODS Colonic manometry (CM) was conducted on a cohort of 30 patients with refractory constipation to assess colonic motility, and 7 of them underwent full-thickness colon biopsy specimens. Another 5 colonic specimens from nonconstipation patients were collected to identify the ICCs by immunohistochemistry. Fecal samples from 14 children diagnosed with refractory constipation and subjecting 28 age-matched healthy children to analysis using high-throughput sequencing of 16S rRNA. RESULTS According to CM results, dividing 30 children with refractory constipation into 2 groups: normal group (n = 10) and dysmotility group (n = 20). Dysmotility subjects showed lower colonic motility. Antegrade propagating pressure waves, retrograde propagating pressure waves, and periodic colonic motor activity were common in normal subjects and rare in dysmotility subjects (32.7 ± 8.9 vs 20.7 ± 13.0/17 h, P < 0.05, 11.5 ± 2.3 vs 9.6 ± 2.3/17 h, P < 0.05, and 5.2 ± 8.9 vs 3.5 ± 6.8 cpm, P < 0.005, respectively), whereas periodic rectal motor activity was more common in dysmotility subjects (3.4 ± 4.8 vs 3.0 ± 3.1 cpm, P < 0.05). Dysmotility subjects exhibited a significantly greater number of preprandial simultaneous pressure waves compared to the normal subjects (32.3 ± 25.0 vs 23.6 ± 13.2/1 h, P < 0.005). Dysmotility subjects displayed a notable decrease in postprandial count of antegrade propagating pressure waves and high amplitude propagating pressure waves when compared to normal subjects (3.9 ± 2.9 vs 6.9 ± 3.5/1 h and 2.3 ± 1.5 vs 5.4 ± 2.9/1 h, respectively, P < 0.05). The number, distribution, and morphology of ICCs were markedly altered in refractory constipation compared children to the controls (P < 0.05). Children diagnosed with refractory constipation displayed a distinct dissimilarity in composition of their intestinal microbiota comparing with control group (P < 0.005). In genus level, Bacteroidetes represented 34.34% and 43.78% in the refractory constipation and control groups, respectively. Faecalibacterium accounted for 3.35% and 12.56%, respectively (P < 0.005). Furthermore, the relative abundances of Faecalibacterium (P < 0.005), Lachnospira (P < 0.05), and Haemophilus (P < 0.05) significantly decreased, whereas those of Parabacteroides (P < 0.05), Alistipes (P < 0.005), Prevotella_2 (P < 0.005), [Ruminococcus]_torques_group (P < 0.005), Barnesiella (P < 0.05), Ruminococcaceae_UCG-002 (P < 0.005), and Christensensenellaceae_R-7_group (P < 0.05) were markedly increased in children with refractory constipation. CONCLUSIONS Dysmotility subjects showed lower colonic motility and an impaired postprandial colonic response. The decreased number and abnormal morphology of colonic ICCs may contribute to the pathogenesis of refractory constipation. Children with refractory constipation exhibited significant variations in microbiota composition across various taxonomic levels compared to the healthy control group. Our findings contribute valuable insights into pathophysiological mechanism underlying refractory constipation and provide evidence to support the exploration of novel therapeutic strategies for affected children.
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Affiliation(s)
- Yi Yuan
- Department of Pediatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China
| | - Yan Lu
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Zhihua Zhang
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Weixia Cheng
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Kunlong Yan
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Yucan Zheng
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Yu Jin
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
| | - Zhifeng Liu
- Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.
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12
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Yu X, Wei M, Yang D, Wu X, Wei H, Xu F. Lactiplantibacillus plantarum Strain FLPL05 Promotes Longevity in Mice by Improving Intestinal Barrier. Probiotics Antimicrob Proteins 2023; 15:1193-1205. [PMID: 35918623 DOI: 10.1007/s12602-022-09933-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/01/2022] [Indexed: 10/16/2022]
Abstract
This study aimed to evaluate the effect of oral administration of probiotic Lactiplantibacillus plantarum FLPL05 on the lifespan and intestinal barrier of aged mice. L. plantarum FLPL05 significantly prolonged the lifespan of naturally aged mice, maintained the integrity of intestinal mucosal barrier, and reduced the inflammation level. The analysis of intestinal microbiota revealed that L. plantarum FLPL05 increased the relative abundance of Firmicutes and decreased the abundance of Bacteroides, accompanied by the increased proportions of Lactobacillus and Desulfovibrio in intestinal microbiota as well as the reduced proportions of Roseburia and Parabacteroides. The intestinal proteomics revealed that the oral administration of L. plantarum FLPL05 significantly upregulated the tight junction and simultaneously inhibited the expression of apoptotic-related proteins. The immunohistochemistry results also indicated that L. plantarum FLPL05 promoted the expression of tight junction proteins (ZO-1 and occludin) and reduced the apoptosis of intestinal cells. In addition, L. plantarum FLPL05 and the fermented supernatant increased the activity of HT-29. L. plantarum FLPL05 prolonged the lifespan by improving the health of the intestinal tract after aging and may be a potential probiotic and nutritional supplement for the elderly people.
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Affiliation(s)
- Xiaomin Yu
- Jiangxi-Oai Joint Research Institute, Nanchang University, 235 Nanjing Donglu, Nanchang, 330047, People's Republic of China
- School of Basic Medical Sciences, Nanchang University, Nanchang, 330047, People's Republic of China
| | - Min Wei
- Jiangxi-Oai Joint Research Institute, Nanchang University, 235 Nanjing Donglu, Nanchang, 330047, People's Republic of China
| | - Dong Yang
- Jiangxi-Oai Joint Research Institute, Nanchang University, 235 Nanjing Donglu, Nanchang, 330047, People's Republic of China
| | - Xiaoli Wu
- College of Basic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, People's Republic of China
| | - Hua Wei
- Jiangxi-Oai Joint Research Institute, Nanchang University, 235 Nanjing Donglu, Nanchang, 330047, People's Republic of China.
| | - Feng Xu
- Jiangxi-Oai Joint Research Institute, Nanchang University, 235 Nanjing Donglu, Nanchang, 330047, People's Republic of China.
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13
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Tran DL, Sintusek P. Functional constipation in children: What physicians should know. World J Gastroenterol 2023; 29:1261-1288. [PMID: 36925458 PMCID: PMC10011959 DOI: 10.3748/wjg.v29.i8.1261] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 12/05/2022] [Accepted: 02/16/2023] [Indexed: 02/28/2023] Open
Abstract
Functional constipation (FC) is considered the most common functional gastrointestinal disorder in children with a pooled global prevalence of 14.4% (95% confidence interval: 11.2-17.6) when diagnosed based on the Rome IV criteria. Its pathophysiological mechanisms are thought be multifactorial and complicated, resulting in difficult management. Currently, the most effective medication, when used in parallel with toilet training, is osmotic laxatives. Children's adherence to medication and parental concern regarding long-term laxative use are the main contributors to treatment failure. Recently, novel therapies with a high safety profile have been developed, such as probiotics, synbiotics, serotonin 5-hydroxytryptamine 4 receptor agonists, chloride channel activators, and herbal and transitional medicines; nonetheless, well-designed research to support the use of these therapies is needed. This review aims to focus on multiple aspects of FC in children, including global prevalence, pathogenesis, diagnostic criteria, tools, as well as conventional and novel treatment options, such as non-pharmacological management, including adequate fiber and fluid intake, physiotherapy, or neuromodulators. We also report that in very difficult cases, surgical intervention may be required.
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Affiliation(s)
- Duc Long Tran
- Thailand and Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Bangkok, Thailand
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho City 9000, Viet Nam
| | - Palittiya Sintusek
- Thai Pediatric Gastroenterology, Hepatology and Immunology Research Unit, Division of Gastroenterology, Department of Pediatrics, King Chulalongkorn Memorial Hospital and Thai Red Cross, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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14
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Gholam-Mostafaei FS, Azimirad M, Naseri K, Nabavi-Rad A, Asadzadeh Aghdaei H, Shahrokh S, Ebrahimi Daryani N, Yadegar A, Zali MR. Intestinal microbiota changes pre- and post-fecal microbiota transplantation for treatment of recurrent Clostridioides difficile infection among Iranian patients with concurrent inflammatory bowel disease. Front Microbiol 2023; 14:1147945. [PMID: 36910213 PMCID: PMC9998922 DOI: 10.3389/fmicb.2023.1147945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 02/08/2023] [Indexed: 02/26/2023] Open
Abstract
INTRODUCTION Patients with inflammatory bowel disease (IBD) are at a greater risk for the recurrence of Clostridioides difficile infection (rCDI) that is triggered by intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) has emerged as a highly effective therapeutic option for this complication. However, little is known about the impact of FMT on intestinal microbiota alterations in rCDI patients suffering from IBD. In this study, we aimed to investigate post-FMT intestinal microbiota alterations in Iranian rCDI patients with underlying IBD. METHODS A total of 21 fecal samples were collected including 14 samples pre- and post-FMT and 7 samples from healthy donors. Microbial analysis was performed by quantitative real-time PCR (RT-qPCR) assay targeting the 16S rRNA gene. The pre-FMT profile and composition of the fecal microbiota were compared to the microbial changes of samples collected 28 days after FMT. RESULTS AND DISCUSSION Overall, the fecal microbiota profile of recipients was more similar to donor samples after the transplantation. We observed a significant increase in the relative abundance of Bacteroidetes post-FMT, compared to the pre-FMT microbial profile. Furthermore, there were remarkable differences between the microbial profile of pre-FMT, post-FMT, and healthy donor samples by PCoA analysis based on the ordination distance. This study demonstrates FMT as a safe and effective approach to restore the indigenous composition of the intestinal microbiota in rCDI patients and ultimately results in the treatment of concurrent IBD.
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Affiliation(s)
- Fahimeh Sadat Gholam-Mostafaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kaveh Naseri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi Daryani
- Department of Gastroenterology and Hepatology, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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15
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Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial. Pediatr Res 2022:10.1038/s41390-022-02289-0. [PMID: 36319696 DOI: 10.1038/s41390-022-02289-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 07/23/2022] [Accepted: 07/29/2022] [Indexed: 03/05/2023]
Abstract
BACKGROUND Oral microbial therapy has been studied as an intervention for a range of gastrointestinal disorders. Though research suggests that microbial exposure may affect the gastrointestinal system, motility, and host immunity in a pediatric population, data have been inconsistent, with most prior studies being in neither a randomized nor placebo-controlled setting. The aim of this randomized, placebo-controlled study was to evaluate the efficacy of a synbiotic on increasing weekly bowel movements (WBMs) in constipated children. METHODS Sixty-four children (3-17 years of age) were randomized to receive a synbiotic (n = 33) comprising mixed-chain length oligosaccharides and nine microbial strains, or placebo (n = 31) for 84 days. Stool microbiota was analyzed on samples collected at baseline and completion. The primary outcome was a change from baseline of WBMs in the treatment group compared to placebo. RESULTS Treatment increased (p < 0.05) the number of WBMs in children with low baseline WBMs, despite broadly distinctive baseline microbiome signatures. Sequencing revealed that low baseline microbial richness in the treatment group significantly anticipated improvements in constipation (p = 0.00074). CONCLUSIONS These findings suggest the potential for (i) multi-species-synbiotic interventions to improve digestive health in a pediatric population and (ii) bioinformatics-based methods to predict response to microbial interventions in children. IMPACT Synbiotic microbial treatment improved the number of spontaneous weekly bowel movements in children compared to placebo. Intervention induced an increased abundance of bifidobacteria in children, compared to placebo. All administered probiotic species were enriched in the gut microbiome of the intervention group compared to placebo. Baseline microbial richness demonstrated potential as a predictive biomarker for response to intervention.
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16
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Dargenio VN, Cristofori F, Dargenio C, Giordano P, Indrio F, Celano G, Francavilla R. Use of Limosilactobacillus reuteri DSM 17938 in paediatric gastrointestinal disorders: an updated review. Benef Microbes 2022; 13:221-242. [PMID: 35212258 DOI: 10.3920/bm2021.0151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Strains of lactobacilli are the most widely used probiotics and can be found in a large variety of food products and food supplements throughout the world. In this study, the evidence on Limosilactobacillus reuteri DSM 17938 (LR DSM 17938) has been reviewed. This species secretes reuterin and other substances singularly or in microvesicles, inhibiting pathogen growth and interacting with the intestinal microbiota and mucosa, restoring homeostasis. The use of LR DSM 17938 has been exploited in several pathological conditions. Preclinical research has shown that this probiotic can ameliorate dysbiosis and, by interacting with intestinal mucosal cells, can raise the pain threshold and promote gastrointestinal motility. These aspects are amongst the significant components in functional gastrointestinal disorders, such as colic and regurgitation in infants, functional abdominal pain and functional constipation in children and adolescents. This strain can decrease the duration of acute diarrhoea and hospitalization for acute gastroenteritis but does not seem to prevent nosocomial diarrhoea and antibiotic-associated diarrhoea. Because of its ability to survive in the gastric environment, it has been tested in Helicobacter pylori infection, showing a significant decrease of antibiotic-associated side effects and a tendency to increase the eradication rate. Finally, all these studies have shown the excellent safety of LR DSM 17938 even at higher dosages. In conclusion data from various clinical trials here reviewed can guide the clinician to find the correct dose, frequency of administration, and therapy duration.
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Affiliation(s)
- V N Dargenio
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
| | - F Cristofori
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
| | - C Dargenio
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
| | - P Giordano
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
| | - F Indrio
- Department of Paediatrics, University of Foggia, Via Pinto 1, 71100 Foggia, Italy
| | - G Celano
- Department of Soil, Plant and Food Science, University of Bari Aldo Moro, Via Amendola 265/a, 70126 Bari, Italy
| | - R Francavilla
- Interdisciplinary Department of Medicine, Paediatric Section. University of Bari Aldo Moro, Children's Hospital 'Giovanni XXIII', Via Amendola 207, 70126 Bari, Italy
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17
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Hartmann P. Editorial: The Microbiome in Hepatobiliary and Intestinal Disease. Front Physiol 2022; 13:893074. [PMID: 35492588 PMCID: PMC9044070 DOI: 10.3389/fphys.2022.893074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 12/12/2022] Open
Affiliation(s)
- Phillipp Hartmann
- Department of Pediatrics, University of California, San Diego, San Diego, CA, United States
- Division of Gastroenterology, Hepatology and Nutrition, Rady Children’s Hospital San Diego, San Diego, CA, United States
- *Correspondence: Phillipp Hartmann,
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18
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Hofman D, Kudla U, Miqdady M, Nguyen TVH, Morán-Ramos S, Vandenplas Y. Faecal Microbiota in Infants and Young Children with Functional Gastrointestinal Disorders: A Systematic Review. Nutrients 2022; 14:974. [PMID: 35267949 PMCID: PMC8912645 DOI: 10.3390/nu14050974] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/15/2022] [Accepted: 02/22/2022] [Indexed: 01/27/2023] Open
Abstract
Functional gastrointestinal disorders (FGIDs) refer to gastrointestinal tract issues that lack clear structural or biochemical causes. Their pathophysiology is still unclear, but gut microbiota alterations are thought to play an important role. This systematic review aimed to provide a comprehensive overview of the faecal microbiota of infants and young children with FGIDs compared to healthy controls. A systematic search and screening of the literature resulted in the inclusion of thirteen full texts. Most papers reported on infantile colic, only one studied functional constipation. Despite methodological limitations, data show alterations in microbial diversity, stability, and colonisation patterns in colicky infants compared to healthy controls. Several studies (eight) reported increases in species of (pathogenic) Proteobacteria, and some studies (six) reported a decrease in (beneficial) bacteria such as Lactobacilli and Bifidobacteria. In addition, accumulation of related metabolites, as well as low-grade inflammation, might play a role in the pathophysiology of infantile colic. Infants and toddlers with functional constipation had significantly lower levels of Lactobacilli in their stools compared to controls. Microbial dysbiosis and related changes in metabolites may be inherent to FGIDs. There is a need for more standardised methods within research of faecal microbiota in FGIDs to obtain a more comprehensive picture and understanding of infant and childhood FGIDs.
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Affiliation(s)
- Denise Hofman
- FrieslandCampina, Stationsplein 1, 3818 LE Amersfoort, The Netherlands;
| | - Urszula Kudla
- FrieslandCampina, Stationsplein 1, 3818 LE Amersfoort, The Netherlands;
| | - Mohamad Miqdady
- Ped. GI, Hepatology & Nutrition Division, Sheikh Khalifa Medical City, P.O. Box 51900, Abu Dhabi 51133, United Arab Emirates;
| | - Thi Viet Ha Nguyen
- Department of Pediatrics, Hanoi Medical University, Hanoi 116001, Vietnam;
| | - Sofía Morán-Ramos
- Unidad de Genomica de Poblaciones, Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico;
| | - Yvan Vandenplas
- Paediatric Gastro-Enterology and Nutrition, Vrije Universiteit Brussel, UZ Brussel, KidZ Health Castle, 1050 Brussels, Belgium;
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19
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Yüksekal G, Sevimli Dikicier B, Koku Aydın B, Yılmaz K, Altındiş M, Köroğlu M. Investigation of intestinal microbiome in chronic spontaneous urticaria patients. Int J Dermatol 2022; 61:988-994. [PMID: 35100439 DOI: 10.1111/ijd.16054] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 11/16/2021] [Accepted: 12/17/2021] [Indexed: 01/14/2023]
Abstract
BACKGROUND Chronic urticaria is a disorder characterized by itchy erythematous plaques with edema lasting 6 weeks or more. The prevalence is 1%, and two thirds of these cases are "chronic spontaneous urticaria (CSU)." Drugs, food, infections, and systemic diseases may be etiologic factors for CSU, although it may be idiopathic. OBJECTIVES The aim of this study was to compare the diversity and distribution of the intestinal microbiome in CSU patients with that of healthy individuals. The hypothesis was to determine the probable association of intestinal microbiome with CSU. METHODS This study was conducted in Sakarya University Training and Research Hospital, Department of Dermatology. In this study, 20 CSU patients and 10 healthy volunteers were included. Stool samples were collected from all participants. 16S RNA sequencing and bioinformatic analysis were performed after isolation of DNA isolation from all samples. RESULTS Diversity in microorganisms, stool pH averages, Bristol scores, and the ratio of Firmicutes/Bacteroidetes were the significant changes between the two groups. LIMITATIONS Due to high cost involved in microbiota studies, only a limited number of patients and volunteers participated. CONCLUSION The alteration in the intestinal microbiota (dysbiosis) may be an essential factor for CSU development and may explain idiopathic cases.
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Affiliation(s)
- Gülcan Yüksekal
- Department of Dermatology, Yenikent State Hospital, Sakarya, Turkey
| | | | - Büşra Koku Aydın
- Department of Dermatology, Sakarya University Medical School, Sakarya, Turkey
| | - Kerem Yılmaz
- Department of Medical Microbiology, Sakarya University Medical School, Sakarya, Turkey
| | - Mustafa Altındiş
- Department of Medical Microbiology, Sakarya University Medical School, Sakarya, Turkey
| | - Mehmet Köroğlu
- Department of Medical Microbiology, Sakarya University Medical School, Sakarya, Turkey
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20
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Abstract
Disturbances in the primary colonization of the infant gut can result in lifelong consequences and have been associated with a range of host conditions. Although early-life factors have been shown to affect infant gut microbiota development, our current understanding of human gut colonization in early life remains limited. To gain more insights into the unique dynamics of this rapidly evolving ecosystem, we investigated the microbiota over the first year of life in eight densely sampled infants (n = 303 total samples). To evaluate the gut microbiota maturation transition toward an adult configuration, we compared the microbiome composition of the infants to that of the Flemish Gut Flora Project (FGFP) population (n = 1,106). We observed the infant gut microbiota to mature through three distinct, conserved stages of ecosystem development. Across these successional gut microbiota maturation stages, the genus predominance was observed to shift from Escherichia over Bifidobacterium to Bacteroides. Both disease and antibiotic treatment were observed to be associated occasionally with gut microbiota maturation stage regression, a transient setback in microbiota maturation dynamics. Although the studied microbiota trajectories evolved to more adult-like constellations, microbiome community typing against the background of the FGFP cohort clustered all infant samples within the (in adults) potentially dysbiotic Bacteroides 2 (Bact2) enterotype. We confirmed the similarities between infant gut microbial colonization and adult dysbiosis. Profound knowledge about the primary gut colonization process in infants might provide crucial insights into how the secondary colonization of a dysbiotic adult gut can be redirected.
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Kittana M, Ahmadani A, Al Marzooq F, Attlee A. Dietary Fat Effect on the Gut Microbiome, and Its Role in the Modulation of Gastrointestinal Disorders in Children with Autism Spectrum Disorder. Nutrients 2021; 13:3818. [PMID: 34836074 PMCID: PMC8618510 DOI: 10.3390/nu13113818] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 10/23/2021] [Accepted: 10/24/2021] [Indexed: 12/19/2022] Open
Abstract
Children with autism spectrum disorder (ASD) report a higher frequency and severity of gastrointestinal disorders (GID) than typically developing (TD) children. GID-associated discomfort increases feelings of anxiety and frustration, contributing to the severity of ASD. Emerging evidence supports the biological intersection of neurodevelopment and microbiome, indicating the integral contribution of GM in the development and function of the nervous system, and mental health, and disease balance. Dysbiotic GM could be a contributing factor in the pathogenesis of GID in children with ASD. High-fat diets may modulate GM through accelerated growth of bile-tolerant bacteria, altered bacterial ratios, and reduced bacterial diversity, which may increase the risk of GID. Notably, saturated fatty acids are considered to have a pronounced effect on the increase of bile-tolerant bacteria and reduction in microbial diversity. Additionally, omega-3 exerts a favorable impact on GM and gut health due to its anti-inflammatory properties. Despite inconsistencies in the data elaborated in the review, the dietary fat composition, as part of an overall dietary intervention, plays a role in modulating GID, specifically in ASD, due to the altered microbiome profile. This review emphasizes the need to conduct future experimental studies investigating the effect of diets with varying fatty acid compositions on GID-specific microbiome profiles in children with ASD.
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Affiliation(s)
- Monia Kittana
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (M.K.); (A.A.)
| | - Asma Ahmadani
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (M.K.); (A.A.)
| | - Farah Al Marzooq
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates;
| | - Amita Attlee
- Department of Nutrition and Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain P.O. Box 15551, United Arab Emirates; (M.K.); (A.A.)
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Wang JK, Yao SK. Roles of Gut Microbiota and Metabolites in Pathogenesis of Functional Constipation. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:5560310. [PMID: 34603471 PMCID: PMC8481049 DOI: 10.1155/2021/5560310] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 09/09/2021] [Indexed: 02/05/2023]
Abstract
Functional constipation (FC), a condition characterized by heterogeneous symptoms (infrequent bowel movements, hard stools, excessive straining, or a sense of incomplete evacuation), is prevalent over the world. It is a multifactorial disorder and can be categorized into four subgroups according to different pathological mechanisms: normal transit constipation (NTC), slow transit constipation (STC), defecatory disorders (DD), and mixed type. Recently, growing evidence from human and animals has pointed that there was a strong association between gut microbiota and FC based on the brain-gut-microbiome axis. Studies have reported that the main characteristics of gut microbiota in FC patients were the relative decrease of beneficial bacteria such as Lactobacillus and Bifidobacterium, the relative increase of potential pathogens, and the reduced species richness. Gut microbiota can modulate gut functions through the metabolites of bacterial fermentation, among which short-chain fatty acids (SCFAs), secondary bile salts (BAs), and methane occupied more important positions and could trigger the release of gut hormones from enteroendocrine cells (EECs), such as 5-hydroxytryptamine (5-HT), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Subsequently, these gut hormones can influence gut sensation, secretion, and motility, primarily through activating specific receptors distributed on smooth muscle cells, enteric neurons, and epithelial cells. However, research findings were inconsistent and even conflicting, which may be partially due to various confounding factors. Future studies should take the associated confounders into consideration and adopt multiomics research strategies to obtain more complete conclusions and to provide reliable theoretical support for exploring new therapeutic targets.
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Affiliation(s)
- Jun-Ke Wang
- Department of Gastroenterology, Peking Union Medical College and Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shu-Kun Yao
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
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Impact of Infant Milk-Type and Childhood Eating Behaviors on Functional Constipation in Preschool Children. J Pediatr Gastroenterol Nutr 2021; 73:e50-e56. [PMID: 33938529 DOI: 10.1097/mpg.0000000000003163] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To investigate the association between functional constipation, infant feeding in early infancy and eating behavior in preschool children. METHODOLOGY A cross-sectional study was undertaken in public and private schools in the state of Sergipe (Northeast of Brazil). The sample calculation was based on a 25% estimate of constipation prevalence in Brazilian children, resulting in a sample size of 1051 children. Functional constipation was assessed using Rome IV criteria. Eating behavior was assessed using the Children's Eating Behavior Questionnaire. Adjusted odds ratios were estimated using a multivariate model. RESULTS The prevalence of functional constipation was 23%. After adjusting for water intake, children with food fussiness were >6 times likely to have constipation (odds ratio [OR] = 6.65; 95% confidence interval [CI] 5.19-8.52). Children who were fed with cow's milk in the first 6 months of age were up to 15.2 times more likely to have functional constipation. Bottle feeding at 0-6 months of age increased the risk of functional constipation at preschool age (whole cow's milk: OR = 17.02; 95% CI 7.33-39.51, infant formula: OR = 6.35; 95% CI 3.42-11.79, mixed breastfeeding: OR = 10.83; 95% CI 4.57-25.69). CONCLUSION Food fussiness and the use of cow's milk-based feeding bottles at 0-6 months of age were associated with functional constipation in preschool children.
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Briguglio M, Dell’Osso B, Porta M. Successful nutrition-based approach in Gilles de la Tourette syndrome heralding drug side effects: A case report and short review. NUTR CLIN METAB 2021. [DOI: 10.1016/j.nupar.2021.01.111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Ostadmohammadi S, Azimirad M, Houri H, Naseri K, Javanmard E, Mirjalali H, Yadegar A, Sadeghi A, Asadzadeh Aghdaei H, Zali MR. Characterization of the gut microbiota in patients with primary sclerosing cholangitis compared to inflammatory bowel disease and healthy controls. Mol Biol Rep 2021; 48:5519-5529. [PMID: 34304365 DOI: 10.1007/s11033-021-06567-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 07/13/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. Its etiology remains largely unknown, although frequent concomitant inflammatory bowel disease (IBD) hints towards common factors underlying intestinal and bile duct inflammation. Herein, we aimed to explore the relative abundance of fecal microbiota in PSC-IBD patients compared to IBD-only subjects and controls. METHODS AND RESULTS We included 14 PSC-IBD patients, 12 IBD-only patients, and 8 healthy controls (HCs). A quantitative real-time PCR (qPCR) assay was used to determine a selection of bacterial phyla, families, and genera. Relative abundance of taxa showed that Bacteroidetes was the most abundant phylum among the patients with PSC-IBD (29.46%) and also HCs (39.34%), whereas the bacterial species belonging to the phylum Firmicutes were the most frequent group in IBD-only subjects (37.61%). The relative abundance of the Enterobacteriaceae family in fecal samples of PSC-IBD patients was similar to those with IBD-only, which was significantly higher than HCs (p value = 0.031), and thus, could be used as a PSC-IBD or IBD-only associated microbial signature. CONCLUSIONS Our findings showed that intestinal microbiota composition in PSC-IBD patients was completely different from that of IBD-only patients. Further studies using large-scale cohorts should be performed to better describe the contribution of the gut microbiota to PSC pathogenesis with underlying IBD.
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Affiliation(s)
- Samaneh Ostadmohammadi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamidreza Houri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kaveh Naseri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ehsan Javanmard
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Mirjalali
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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García Contreras AA, Vásquez Garibay EM, Sánchez Ramírez CA, Fafutis Morris M, Delgado Rizo V. Factors associated with the stool characteristics of children with cerebral palsy and chronic constipation. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2021; 112:41-46. [PMID: 31830793 DOI: 10.17235/reed.2019.6313/2019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND chronic constipation is a common gastrointestinal problem in children with cerebral palsy and several factors can influence the stool frequency, consistency and pH in these cases. AIM to identify the association of dietary factors, use of anticonvulsants and family history of constipation with the stool characteristics of children with cerebral palsy and chronic constipation. METHODS an analytical cross-sectional study was performed of 45 children with cerebral palsy and chronic constipation that included 19 females and 26 males, aged 37 ± 13 months. Dietary factors, the use of anticonvulsants and family history were analyzed. Stool frequency, consistency (Bristol Stool Form Scale) and pH (using a pH-meter) were also determined. RESULTS there was a positive correlation between stool frequency and the consumption of oilseeds (r = 0.339, p = 0.023). There was a negative correlation between hard stools and fluid intake (r = -0.336, p = 0.042) and between stool pH and the consumption of cereals rich in insoluble fiber, high soluble fiber vegetables, carrots and potatoes (r = -0.339, p = 0.030; r = -0.308, p = 0.044; r = -0.336, p = 0.027; r = -0.307, p = 0.045, respectively). An association was also identified between the use of anticonvulsant polytherapy and hard stools (OR = 14.2 [95% CI 1.16-174], p = 0.038). There was no association between family history and constipation. CONCLUSIONS rich-fiber food consumption, fluids intake and anticonvulsant polytherapy were associated with the stool characteristics of children with cerebral palsy and chronic constipation.
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Affiliation(s)
- Andrea A García Contreras
- Instituto de Nutrición Humana, Hospital Civil de Guadalajara Dr. Juan I. Menchaca. Guadalajara, México
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Avelar Rodriguez D, Popov J, Ratcliffe EM, Toro Monjaraz EM. Functional Constipation and the Gut Microbiome in Children: Preclinical and Clinical Evidence. Front Pediatr 2021; 8:595531. [PMID: 33553067 PMCID: PMC7856458 DOI: 10.3389/fped.2020.595531] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2020] [Accepted: 12/21/2020] [Indexed: 12/22/2022] Open
Abstract
Functional constipation is a common condition in childhood with significant impact on patients' quality of life and on health care resources. Functional constipation is characterized by decreased bowel movements and/or hard stools, which cause significant distress for children and their caregivers. While the term "functional" may imply the absence of organic causes with a focus on behavioral aspects, 40% of children continue to have symptoms beyond conventional management with one in four children continuing to experience constipation into adulthood. The refractory and chronic nature of constipation highlights the importance of considering a range of pathophysiological mechanisms, including the potential role of the gut microbiome. In this review, we provide an overview of preclinical and clinical studies that focus on the potential mechanisms through which the gut microbiome might contribute to the clinical presentation of functional constipation in pediatrics.
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Affiliation(s)
- David Avelar Rodriguez
- Department of Pediatric Gastroenterology and Nutrition, Instituto Nacional de Pediatría, Mexico City, Mexico
- Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada
| | - Jelena Popov
- College of Medicine and Health, University College Cork, Cork, Ireland
| | - Elyanne M. Ratcliffe
- Division of Gastroenterology and Nutrition, Department of Pediatrics, McMaster University, Hamilton, ON, Canada
| | - Erick Manuel Toro Monjaraz
- Department of Pediatric Gastroenterology and Nutrition, Instituto Nacional de Pediatría, Mexico City, Mexico
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Jomehzadeh N, Javaherizadeh H, Amin M, Rashno M, Teimoori A. Quantification of Intestinal Lactobacillus Species in Children with Functional Constipation by Quantitative Real-Time PCR. Clin Exp Gastroenterol 2020; 13:141-150. [PMID: 32440191 PMCID: PMC7211309 DOI: 10.2147/ceg.s250755] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 04/17/2020] [Indexed: 12/12/2022] Open
Abstract
Background Functional constipation is a common and annoying gastrointestinal disorder among children worldwide in which the intestinal microbiota composition plays a fundamental role. This study aimed to compare the quantity of main intestinal Lactobacillus species in constipated children and healthy controls. Materials and Methods Fecal samples were collected from 40 children fulfilling Rome IV criteria for functional constipation and 40 healthy volunteers. Quantitative real-time polymerase chain reaction (qPCR) method with species-specific primers was used to investigate seven main Lactobacillus species in fecal samples. Results Lactobacillus strains of the patient group were different from the healthy controls, main differences being noticeable decrease in the population quantity of Lactobacillus reuteri (mean 102.61 CFU/gram feces) and lower abundance of Lactobacillus fermentum (p<0.0001). Conclusion Lactobacillus species might be quantitatively altered in childhood functional constipation. Our findings on the different species of Lactobacillus population showed significantly decreased quantity in the patient group compared with the healthy subjects.
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Affiliation(s)
- Nabi Jomehzadeh
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hazhir Javaherizadeh
- Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Khouzestan, Iran
| | - Mansour Amin
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.,Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohammad Rashno
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Teimoori
- Department of Virology, Faculty of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran
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Gomes DOVS, Morais MBD. GUT MICROBIOTA AND THE USE OF PROBIOTICS IN CONSTIPATION IN CHILDREN AND ADOLESCENTS: SYSTEMATIC REVIEW. ACTA ACUST UNITED AC 2019; 38:e2018123. [PMID: 31778407 PMCID: PMC6909257 DOI: 10.1590/1984-0462/2020/38/2018123] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 08/30/2018] [Indexed: 12/12/2022]
Abstract
Objective: To perform a systematic review of literature data on gut microbiota and the efficacy of probiotics for the treatment of constipation in children and adolescents. Data source: The research was performed in the PubMed, the Scientific Electronic Library Online (SciELO) and the Latin American and Caribbean Health Sciences Literature (LILACS) databases in English, Portuguese and Spanish. All original articles that mentioned the evaluation of the gut microbiota or the use of probiotics in children with constipation in their title and abstract were selected. Data synthesis: 559 articles were found, 47 of which were selected for reading. From these, 12 articles were included; they studied children and adolescents divided into two categories: a gut microbiota evaluation (n=4) and an evaluation of the use of probiotics in constipation therapy (n=8). The four papers that analyzed fecal microbiota used different laboratory methodologies. No typical pattern of gut microbiota was found. Regarding treatment, eight clinical trials with heterogeneous methodologies were found. Fifteen strains of probiotics were evaluated and only one was analyzed in more than one article. Irregular beneficial effects of probiotics have been demonstrated in some manifestations of constipation (bowel frequency or consistency of stool or abdominal pain or pain during a bowel movement or flatulence). In one clinical trial, a complete control of constipation without the use of laxatives was obtained. Conclusions: There is no specific pattern of fecal microbiota abnormalities in constipation. Despite the probiotics’ positive effects on certain characteristics of the intestinal habitat, there is still no evidence to recommend it in the treatment of constipation in pediatrics.
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Chen S, Ou Y, Zhao L, Li Y, Qiao Z, Hao Y, Ren F. Differential Effects of Lactobacillus casei Strain Shirota on Patients With Constipation Regarding Stool Consistency in China. J Neurogastroenterol Motil 2019; 25:148-158. [PMID: 30646486 PMCID: PMC6326197 DOI: 10.5056/jnm17085] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 07/11/2018] [Accepted: 07/31/2018] [Indexed: 12/12/2022] Open
Abstract
Background/Aims Probiotics are expected to confer benefits on patients with constipation, but how probiotics act on constipated patients with variable stool consistencies remains unclear. We investigated the effect of Lactobacillus casei strain Shirota (LcS) on constipation-related symptoms, especially stool consistency, of constipated patients. Methods Constipated patients meeting the Rome III criteria were divided into 3 groups according to the Bristol Stool Form Scale (BSFS): hard (hard stool [HS], BSFS < 3), normal (normal stool [NS], ≤ 3 BSFS ≤ 4), and soft (soft stool [SS], 4 < BSFS ≤ 5) stools. Subjects in each group consumed a probiotic beverage containing 1010 colony-forming units of LcS daily for 28 days. Results LcS intervention significantly alleviated constipation-related symptoms and increased defecation frequency in all subjects. Four weeks of LcS supplementation softened the hard stools in HS, hardened the soft stools in SS, and did not alter the ideal stool consistency in NS. The short-chain fatty acid (SCFA) concentrations were highest in SS, followed by NS and HS. LcS intervention increased the stool SCFA levels in HS but reduced or did not alter the levels in NS and SS. LcS intervention increased the Pseudobutyrivibrio and Roseburia abundances in HS and decreased the Pseudobutyrivibrio abundance in SS. Conclusions LcS supplementation improved the constipation-related symptoms in constipated subjects. Differences in baseline stool consistency could result in different anti-constipation effects of LcS intervention. LcS balanced the stool consistency—softened the HS and hardened the SS. These effects could be associated with modulation of the gut microbiota and SCFA production.
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Affiliation(s)
- Shanbin Chen
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China
| | - Yangwenshan Ou
- Beijing Laboratory for Food Quality and Safety, Beijing, China
| | - Liang Zhao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.,Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, Beijing, China
| | - Yang Li
- Science and Public Relations Office, Yakult (China) Corporation, Shanghai, China
| | - Zhenxing Qiao
- Science and Public Relations Office, Yakult (China) Corporation, Shanghai, China
| | - Yanling Hao
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.,Beijing Laboratory for Food Quality and Safety, Beijing, China.,Beijing Key Laboratory of Detection and Control of Spoilage Organisms and Pesticide Residues in Agricultural Products, Beijing University of Agriculture, Beijing, China
| | - Fazheng Ren
- Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.,Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, Beijing, China
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Mohamadkhani A. Gut Microbiota and Fecal Metabolome Perturbation in Children with Autism Spectrum Disorder. Middle East J Dig Dis 2018; 10:205-212. [PMID: 31049167 PMCID: PMC6488507 DOI: 10.15171/mejdd.2018.112] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 07/18/2018] [Indexed: 02/06/2023] Open
Abstract
The brain-intestinal axis concept describes the communication between the intestinal
microbiota as an ecosystem of a number of dynamic microorganisms and the brain. The
composition of the microbial community of the human gut is important for human health
by influencing the total metabolomic profile. In children with autism spectrum disorder
(ASD), the composition of the fecal microbiota and their metabolic products has a different
configuration of the healthy child. An imbalance in the metabolite derived from the microbiota
in children with ASD affect brain development and social behavior. In this article, we
review recent discoveries about intestinal metabolites derived from microbiota based on
high-yield molecular studies in children with ASD as part of the "intestinal brain axis"
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Affiliation(s)
- Ashraf Mohamadkhani
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Pinheiro I, Robinson L, Verhelst A, Marzorati M, Winkens B, den Abbeele PV, Possemiers S. A yeast fermentate improves gastrointestinal discomfort and constipation by modulation of the gut microbiome: results from a randomized double-blind placebo-controlled pilot trial. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 17:441. [PMID: 28870194 PMCID: PMC5584023 DOI: 10.1186/s12906-017-1948-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 08/24/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Constipation and symptoms of gastrointestinal discomfort such as bloating are common among otherwise healthy individuals, but with significant impact on quality of life. Despite the recognized contribution of the gut microbiome to this pathology, little is known about which group(s) of microorganism(s) are playing a role. A previous study performed in vitro suggests that EpiCor® fermentate has prebiotic-like properties, being able to favorably modulate the composition of the gut microbiome. Therefore, the aim of this study was to investigate the effects of EpiCor fermentate in a population with symptoms of gastrointestinal discomfort and reduced bowel movements and to evaluate its effect at the level of the gut microbiome. METHODS This pilot study was performed according to a randomized, double-blind, placebo-controlled parallel design. Eighty subjects with symptoms of gastrointestinal discomfort and constipation were allocated to one of two trial arms (placebo or EpiCor fermentate). Randomization was done in a stratified manner according to symptom severity, resulting in two subgroups of patients: severe and moderate. Daily records of gastrointestinal symptoms were assessed on a 5-point scale, and also stool frequency and consistency were documented during a 2-week run-in and a 6-week intervention phases. Averages over two-week intervals were calculated. Constipation-associated quality of life and general perceived stress were assessed at baseline and after 3 and 6 weeks of intervention. Fecal samples were also collected at these same time points. RESULTS EpiCor fermentate led to a significant improvement of symptoms such as bloating/distension (p = 0.033 and p = 0.024 after 2 and 4 weeks of intervention, respectively), feeling of fullness (p = 0.004 and p = 0.023 after 2 and 4 weeks of intervention, respectively) and general daily scores (p = 0.046 after 2 weeks of intervention) in the moderate subgroup. A significant improvement in stool consistency was observed for the total population (p = 0.023 after 2 weeks of intervention) as well as for the severe subgroup (p = 0.046 after 2 weeks of intervention), and a nearly significant increase in stool frequency was detected for the total cohort (p = 0.083 and p = 0.090 after 2 and 4 weeks of intervention, respectively). These effects were accompanied by an improvement in constipation-associated quality of life and general perceived stress, particularly in the moderate subgroup. Members of the families Bacteroidaceae and Prevotellaceae, two groups of bacteria that have been previously reported to be deficient in constipated patients, were found to increase with EpiCor fermentate in the severe subgroup. In the moderate subgroup, a significant increase in Akkermansia muciniphila was observed. CONCLUSIONS Despite the relatively low dose administered (500 mg/day), particularly when comparing to the high recommended doses for prebiotic fibers, EpiCor fermentate was able to modulate the composition of the gut microbiome, resulting in improvement of constipation-associated symptoms. Conversely, the reported increase in bowel movements may have altered the gut microbial community by increasing those groups of bacteria that are better adapted to a faster gastrointestinal transit time. TRIAL REGISTRATION NCT03051399 at ClinicalTrials.gov. Retrospectively registered. Registration date: 13 February 2017.
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Affiliation(s)
| | - Larry Robinson
- Embria Health Sciences, 2105 SE Creekview Dr, Ankeny, IA 50021 USA
| | - An Verhelst
- ProDigest, Technologiepark 3, 9052 Ghent, Belgium
| | - Massimo Marzorati
- Center of Microbial Ecology and Technology (CMET), University of Ghent, Coupure Links 653, 9000 Ghent, Belgium
| | - Björn Winkens
- Department of Methodology and Statistics, Faculty of Health Medicine and Life Sciences, University of Maastricht, Maastricht, 6200 MD The Netherlands
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Analysis of the Duodenal Microbiome in Autistic Individuals: Association With Carbohydrate Digestion. J Pediatr Gastroenterol Nutr 2017; 64:e110-e116. [PMID: 27811623 DOI: 10.1097/mpg.0000000000001458] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES There is evidence that symptoms of maldigestion or malabsorption in autistic individuals are related to changes in the indigenous microbiota. Analysis of colonic bacteria has revealed microbial dysbiosis in children with autism; however, characteristics of the duodenal microbiome are not well described. In the present study the microbiome of the duodenal mucosa of subjects with autism was evaluated for dysbiosis, bacteria overgrowth, and microbiota associated with carbohydrate digestion. The relationship between the duodenal microbiome and disaccharidase activity was analyzed in biopsies from 21 autistic subjects and 19 children without autism. METHODS Microbiota composition was determined by 16S ribosomal RNA gene sequencing, and disaccharidase activity via biochemical assays. RESULTS Although subjects with autism had a higher frequency of constipation (P < 0.005), there was no difference in disaccharidase activity between groups. In addition, no differences in microbiome diversity (species richness and evenness) were observed. Bacteria belonging to the genus Burkholderia were more abundant in subjects with autism, whereas members of the genus Neisseria were less abundant. At the species level, a relative decrease in abundance of 2 Bacteroides species and Escherichia coli was found in autistic individuals. There was a positive correlation between the abundance of Clostridium species, and disaccharidase activity, in autistic individuals. CONCLUSIONS There are a variety of changes at the genus and species level in duodenal microbiota in children with autism that could be influenced by carbohydrate malabsorption. These observations could be affected by variations in individual diets, but also may represent a more pervasive dysbiosis that results in metabolites that affect the behavior of autistic children.
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