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Wei Y, Chen S, Ling Y, Wang W, Huang Y. Multi-omics revealed that the postbiotic of hawthorn-probiotic alleviated constipation caused by loperamide in elderly mice. Front Nutr 2025; 12:1498004. [PMID: 40070478 PMCID: PMC11895004 DOI: 10.3389/fnut.2025.1498004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 02/05/2025] [Indexed: 03/14/2025] Open
Abstract
BackgroundConstipation is a prevalent and recurrent gastrointestinal disorder causing significant discomfort. However, current treatments often prove ineffective. Previous research indicates that the postbiotic derived from a combination of hawthorn and probiotics can alleviate constipation. This study aimed to investigate its mechanisms using loperamide-induced constipation in aged KM mice.MethodsConstipated mice were divided into groups receiving 10% lactulose (Y), hawthorn extract (S), probiotics (F), and the postbiotic of hawthorn-probiotic (FS). UPLC–MS metabolomics identified constituents of F, S, and FS. Network pharmacological analysis identified targets affected by FS. RT-qPCR assessed target expression in mouse colons, along with IL-6 and IL-17A levels. Molecular docking with AutoDock Tools1.5.6 evaluated interactions between FS components and targets. ex vivo colonic organ culture and RT-qPCR assessed target changes. Molecular dynamics analysis further scrutinized interactions. Targeted metabolomics measured short-chain fatty acid levels in mouse stool.ResultsUPLC–MS metabolomics revealed distinct profiles for F, S, and FS, with FS showing decreased toxic substances and increased beneficial ones compared to S. Network pharmacology identified 20 cross-targets of FS in constipation. RT-qPCR showed decreased NR1I2 and SULT1A1 and increased GLP-2r in FS-treated mice. Inflammatory cytokines IL-6 and IL-17A were also reduced. ex vivo colonic organ culture and molecular docking identified effective combinations such as TNF-Baicalin and AQP3-Quinacridone. RMSD, RMSF, and RG analyses indicated favorable interactions between small molecules and targets. Targeted metabolomics revealed differing short-chain fatty acid contents in feces among groups.ConclusionThe postbiotic of hawthorn-probiotic alleviates constipation by regulating intestinal water and sodium metabolism, maintaining the intestinal barrier and gut flora, promoting epithelial cell proliferation, reducing inflammatory responses, and improving short-chain fatty acid metabolism.
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Affiliation(s)
- Yu Wei
- Guangzhou University of Chinese Medicine, Guangzhou, China
- Basic Medical Science College, Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shuai Chen
- Yunnan University of Chinese Medicine, Kunming, China
| | - Ying Ling
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wei Wang
- Guangzhou University of Chinese Medicine, Guangzhou, China
- The First Clinical Medical School, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yali Huang
- Guangzhou University of Chinese Medicine, Guangzhou, China
- Basic Medical Science College, Guangzhou University of Chinese Medicine, Guangzhou, China
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Cosier DJ, Lambert K, Neale EP, Probst Y, Charlton K. The effect of oral synbiotics on the gut microbiota and inflammatory biomarkers in healthy adults: a systematic review and meta-analysis. Nutr Rev 2025; 83:e4-e24. [PMID: 38341803 PMCID: PMC12086677 DOI: 10.1093/nutrit/nuae002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/13/2024] Open
Abstract
CONTEXT Prior research has explored the effect of synbiotics, the combination of probiotics and prebiotics, on the gut microbiota in clinical populations. However, evidence related to the effect of synbiotics on the gut microbiota in healthy adults has not been reviewed to date. OBJECTIVE A systematic review and meta-analysis was conducted to comprehensively investigate the effect of synbiotics on the gut microbiota and inflammatory markers in populations of healthy adults. DATA SOURCES Scopus, PubMed, Web of Science, ScienceDirect, MEDLINE, CINAHL, and The Cochrane Library were systematically searched to retrieve randomized controlled trials examining the primary outcome of gut microbiota or intestinal permeability changes after synbiotic consumption in healthy adults. Secondary outcomes of interest were short-chain fatty acids, inflammatory biomarkers, and gut microbiota diversity. DATA EXTRACTION Weighted (WMD) or standardized mean difference (SMD) outcome data were pooled in restricted maximum likelihood models using random effects. Twenty-seven articles reporting on 26 studies met the eligibility criteria (n = 1319). DATA ANALYSIS Meta-analyses of 16 studies showed synbiotics resulted in a significant increase in Lactobacillus cell count (SMD, 0.74; 95% confidence interval [CI], 0.15, 1.33; P = 0.01) and propionate concentration (SMD, 0.22; 95% CI, 0.02, 0.43; P = 0.03) compared with controls. A trend for an increase in Bifidobacterium relative abundance (WMD, 0.97; 95% CI, 0.42, 2.52; P = 0.10) and cell count (SMD, 0.82; 95% CI, 0.13, 1.88; P = 0.06) was seen. No significant differences in α-diversity, acetate, butyrate, zonulin, IL-6, CRP, or endotoxins were observed. CONCLUSION This review demonstrates that synbiotics modulate the gut microbiota by increasing Lactobacillus and propionate across various healthy adult populations, and may result in increased Bifidobacterium. Significant variations in synbiotic type, dose, and duration should be considered as limitations when applying findings to clinical practice. SYSTEMATIC REVIEW REGISTRATION PROSPERO no. CRD42021284033.
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Affiliation(s)
- Denelle J Cosier
- School of Medicine, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia
| | - Kelly Lambert
- School of Medicine, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia
| | - Elizabeth P Neale
- School of Medicine, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia
| | - Yasmine Probst
- School of Medicine, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia
| | - Karen Charlton
- School of Medicine, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia
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Magistrelli L, Contaldi E, Visciglia A, Deusebio G, Pane M, Amoruso A. The Impact of Probiotics on Clinical Symptoms and Peripheral Cytokines Levels in Parkinson's Disease: Preliminary In Vivo Data. Brain Sci 2024; 14:1147. [PMID: 39595910 PMCID: PMC11592242 DOI: 10.3390/brainsci14111147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/11/2024] [Accepted: 11/14/2024] [Indexed: 11/28/2024] Open
Abstract
Introduction. Previous studies have shown that probiotics have positive effects on both motor and non-motor symptoms in Parkinson's disease (PD). Additionally, in preclinical settings, probiotics have demonstrated the ability to counteract neuronal loss and alpha-synuclein aggregation, important pathological hallmarks of PD. Notably, preliminary in vitro studies have revealed the immunomodulatory properties of probiotics. This study aims to evaluate the impact of probiotics on symptoms and peripheral cytokines levels in PD patients compared to placebo. Methods. Patients were enrolled and blindly randomized to receive either active probiotics (comprising Bifidobacterium animalis subsp. lactis BS01 LMG P-21384, Bifidobacterium longum BL03 DSM 16603, Bifidobacterium adolescentis BA02 DSM 18351, Fructo-oligosaccharides and Maltodextrin-Group A) or placebo (Maltodextrin-Group B). Clinical evaluations and plasma levels cytokines (TNF-α, IFN-γ, IL-6, and TGF-β) were also assessed at enrollment and after 12 weeks. Anti-parkinsonian therapy remained stable throughout the study. Results. Forty PD patients were recruited. After 12 weeks, Group A showed significant improvement in motor symptoms (UPDRS III: 13.89 ± 4.08 vs. 12.74 ± 4.57, p = 0.028) and non-motor symptoms (NMSS: 34.32 ± 21.41 vs. 30.11 ± 19.89, p = 0.041), with notable improvement in the gastrointestinal sub-item (3.79 ± 4.14 vs. 1.89 ± 2.54, p = 0.021). A reduction of IFN-γ levels was observed in both groups, but group A also showed a significant decrease in IL-6 and a slight increase in the anti-inflammatory cytokine TGF-β. Conclusions. Our data suggest that probiotics may modulate peripheral cytokines levels and improve clinical symptoms in PD patients. Probiotics may, therefore, represent a valuable adjunctive therapy to conventional anti-parkinsonian drugs.
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Affiliation(s)
- Luca Magistrelli
- Parkinson Institute Milan, ASST G.Pini-CTO, Via Bignami 1, 20126 Milan, Italy;
| | - Elena Contaldi
- Parkinson Institute Milan, ASST G.Pini-CTO, Via Bignami 1, 20126 Milan, Italy;
| | - Annalisa Visciglia
- Probiotical Research S.r.l., Via Mattei 3, 28100 Novara, Italy; (A.V.); (G.D.); (M.P.); (A.A.)
| | - Giovanni Deusebio
- Probiotical Research S.r.l., Via Mattei 3, 28100 Novara, Italy; (A.V.); (G.D.); (M.P.); (A.A.)
| | - Marco Pane
- Probiotical Research S.r.l., Via Mattei 3, 28100 Novara, Italy; (A.V.); (G.D.); (M.P.); (A.A.)
| | - Angela Amoruso
- Probiotical Research S.r.l., Via Mattei 3, 28100 Novara, Italy; (A.V.); (G.D.); (M.P.); (A.A.)
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Wei Y, Huang N, Ye X, Liu M, Wei M, Huang Y. The postbiotic of hawthorn-probiotic ameliorating constipation caused by loperamide in elderly mice by regulating intestinal microecology. Front Nutr 2023; 10:1103463. [PMID: 37006920 PMCID: PMC10061020 DOI: 10.3389/fnut.2023.1103463] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 02/22/2023] [Indexed: 03/18/2023] Open
Abstract
Background Constipation is common gastrointestinal disorder with high prevalence and recurrence, making people suffering. However, the treatment for constipation remains ineffectual. We aimed to the study the effects and mechanisms of postbiotic of hawthorn-probiotic on loperamide modeled old KM mice. Methods Constipated mice were grouped and treated with 10% lactulose (Y), hawthorn group (S), probiotic group (F) and postbiotic of hawthorn-probiotic (FS). Fecal changes were observed. AQP3 and Enac-γ were measured by RT-qPCR and Western blotting, intestinal barrier by H&E and immunofluorescence staining, cell proliferation and apoptosis by CCK8 and flow cytometry. Gut microbiota was further determined by 16 s rRNA sequence of feces. Results Postbiotic of hawthorn-probiotic improved intestinal movement and pathomorphology, elevated AQP3, Enac-γ and mucin-2 expression, accompanied by decreased serum TNF-α and cell apoptosis, but increased proliferation. Furthermore, it modified the gut microbiota of constipated mice, featured by upregulation of Lactobacillaceae. Conclusion Postbiotic of hawthorn-probiotic relieved constipation by combined effects of regulating intestinal water and sodium metabolism, maintain intestinal barrier and gut microflora.Graphical Abstract.
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Affiliation(s)
- Yu Wei
- Basic Medical Science College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Na Huang
- The Eighth School of Clinical Medicine (Foshan Hospital of TCM), Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Xinyu Ye
- Basic Medical Science College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Meng Liu
- Basic Medical Science College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Meilian Wei
- Basic Medical Science College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Yali Huang
- Basic Medical Science College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
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Araújo MM, Botelho PB. Probiotics, prebiotics, and synbiotics in chronic constipation: Outstanding aspects to be considered for the current evidence. Front Nutr 2022; 9:935830. [PMID: 36570175 PMCID: PMC9773270 DOI: 10.3389/fnut.2022.935830] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 11/14/2022] [Indexed: 12/13/2022] Open
Abstract
This integrative aimed to evaluate the effects and the potential mechanism of action of prebiotics, probiotics, and synbiotics on constipation-associated gastrointestinal symptoms and to identify issues that still need to be answered. A literature search was performed in the PubMed database. Animal models (n = 23) and clinical trials (n = 39) were included. In animal studies, prebiotic, probiotic, and synbiotic supplementation showed a decreased colonic transit time (CTT) and an increase in the number and water content of feces. In humans, inulin is shown to be the most promising prebiotic, while B. lactis and L. casei Shirota probiotics were shown to increase defecation frequency, the latter strain being more effective in improving stool consistency and constipation symptoms. Overall, synbiotics seem to reduce CTT, increase defecation frequency, and improve stool consistency with a controversial effect on the improvement of constipation symptoms. Moreover, some aspects of probiotic use in constipation-related outcomes remain unanswered, such as the best dose, duration, time of consumption (before, during, or after meals), and matrices, as well as their effect and mechanisms on the regulation of inflammation in patients with constipation, on polymorphisms associated with constipation, and on the management of constipation via 5-HT. Thus, more high-quality randomized control trials (RCTs) evaluating these lacking aspects are necessary to provide safe conclusions about their effectiveness in managing intestinal constipation.
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Almutairi R, Basson AR, Wearsh P, Cominelli F, Rodriguez-Palacios A. Validity of food additive maltodextrin as placebo and effects on human gut physiology: systematic review of placebo-controlled clinical trials. Eur J Nutr 2022; 61:2853-2871. [PMID: 35230477 PMCID: PMC9835112 DOI: 10.1007/s00394-022-02802-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 01/06/2022] [Indexed: 01/16/2023]
Abstract
PURPOSE Maltodextrin (MDX) is a polysaccharide food additive commonly used as oral placebo/control to investigate treatments/interventions in humans. The aims of this study were to appraise the MDX effects on human physiology/gut microbiota, and to assess the validity of MDX as a placebo-control. METHODS We performed a systematic review of randomized-placebo-controlled clinical trials (RCTs) where MDX was used as an orally consumed placebo. Data were extracted from study results where effects (physiological/microbial) were attributed (or not) to MDX, and from study participant outcomes data, before-and-after MDX consumption, for post-publication 're-analysis' using paired-data statistics. RESULTS Of two hundred-sixteen studies on 'MDX/microbiome', seventy RCTs (n = 70) were selected for analysis. Supporting concerns regarding the validity of MDX as a placebo, the majority of RCTs (60%, CI 95% = 0.48-0.76; n = 42/70; Fisher-exact p = 0.001, expected < 5/70) reported MDX-induced physiological (38.1%, n = 16/42; p = 0.005), microbial metabolite (19%, n = 8/42; p = 0.013), or microbiome (50%, n = 21/42; p = 0.0001) effects. MDX-induced alterations on gut microbiome included changes in the Firmicutes and/or Bacteroidetes phyla, and Lactobacillus and/or Bifidobacterium species. Effects on various immunological, inflammatory markers, and gut function/permeability were also documented in 25.6% of the studies (n = 10/42). Notably, there was considerable variability in the direction of effects (decrease/increase), MDX dose, form (powder/pill), duration, and disease/populations studied. Overall, only 20% (n = 14/70; p = 0.026) of studies cross-referenced MDX as a justifiable/innocuous placebo, while 2.9% of studies (n = 2/70) acknowledged their data the opposite. CONCLUSION Orally-consumed MDX often (63.9% of RCTs) induces effects on human physiology/gut microbiota. Such effects question the validity of MDX as a placebo-control in human clinical trials.
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Affiliation(s)
- Rawan Almutairi
- Department of Pathology, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH, 44106, USA
| | - Abigail Raffner Basson
- Department of Medicine and Division of Gastroenterology & Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Pamela Wearsh
- Department of Pathology, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH, 44106, USA
| | - Fabio Cominelli
- Department of Medicine and Division of Gastroenterology & Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
- University Hospitals Research and Education Institute, University Hospital Cleveland Medical Center, Cleveland, OH, USA
| | - Alexander Rodriguez-Palacios
- Department of Medicine and Division of Gastroenterology & Liver Diseases, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
- Digestive Health Research Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
- Germ-Free and Gut Microbiome Core, Cleveland Digestive Diseases Research Core Center, Case Western Reserve University, 2109 Adelbert Road, Cleveland, OH, USA.
- University Hospitals Research and Education Institute, University Hospital Cleveland Medical Center, Cleveland, OH, USA.
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Ascanelli S, Bombardini C, Chimisso L, Carcoforo P, Turroni S, D’Amico F, Caniati ML, Baldi E, Tugnoli V, Morotti C, Valpiani G, Bazzocchi G. Trans-anal irrigation in patients with multiple sclerosis: Efficacy in treating disease-related bowel dysfunctions and impact on the gut microbiota: A monocentric prospective study. Mult Scler J Exp Transl Clin 2022; 8:20552173221109771. [PMID: 35832690 PMCID: PMC9272186 DOI: 10.1177/20552173221109771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2022] [Accepted: 06/10/2022] [Indexed: 11/17/2022] Open
Abstract
Background Constipation and faecal incontinence are not so uncommon in patients with multiple sclerosis, impairing quality of life. The gut microbiota is altered in multiple sclerosis patients and likely contributes to disease pathogenesis. Trans-anal irrigation has been proven to allow treatment of neurogenic bowel dysfunction and may affect gut microbiota. Objectives The primary outcome was trans-anal irrigation effectiveness on constipation and faecal incontinence. The secondary outcome was gut microbiota profiling compared to healthy subjects and during trans-anal irrigation adoption. Methods We conducted a prospective cohort study on multiple sclerosis patients, screened with Patient Assessment of Constipation Quality of Life questionnaire before undergoing constipation and faecal incontinence scoring, abdomen X-ray for intestinal transit time, compilation of food and evacuation diaries and faecal sample collection for gut microbiota analysis before and after 4 weeks of trans-anal irrigation. Results and Conclusions Eighty patients were screened of which nearly half had intestinal symptoms. The included population (n = 37) was predominantly composed of women with significantly longer disease duration, higher mean age and disability than the excluded one ( p < 0.05). Twelve patients completed the trans-anal irrigation phase, which led to significant improvement of bowel dysfunction symptom-related quality of life, increase in gut microbiota diversity and reduction of the proportions of pro-inflammatory taxa ( p < 0.05). Trans-anal irrigation was safe, satisfactory and could help counteract multiple sclerosis-related dysbiosis.
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Affiliation(s)
| | | | | | - Paolo Carcoforo
- Department of Morphology, Surgery and Experimental Medicine, Colorectal Unit, Section General Surgery, University Hospital of Ferrara, Ferrara, Italy
| | - Silvia Turroni
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Federica D’Amico
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | | | - Valeria Tugnoli
- Department of Neuroscience Rehabilitation, Multiple Sclerosis Center, Unit of Neurology, University Hospital of Ferrara, Ferrara, Italy
| | | | - Giorgia Valpiani
- Accreditation Office Quality Research Innovation, University Hospital of Ferrara, Ferrara, Italy
| | - Gabriele Bazzocchi
- Montecatone Rehabilitation Institute, University of Bologna, Imola, Italy
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Effects of Lactobacillus plantarum P9 Probiotics on Defecation and Quality of Life of Individuals with Chronic Constipation: Protocol for a Randomized, Double-Blind, Placebo-Controlled Clinical Trial. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:4144321. [PMID: 35733625 PMCID: PMC9208957 DOI: 10.1155/2022/4144321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 03/25/2022] [Accepted: 04/23/2022] [Indexed: 11/17/2022]
Abstract
Background Although probiotics have been shown to improve constipation-related symptoms, a clear consensus on the use of probiotics as a constipation-relieving agent has not been reached, which is attributed to the limited available evidence and inconsistent protocols used in existing studies. Method A randomized, double-blind, placebo-controlled clinical trial is designed to study the efficiency and possible mechanism of action of probiotics for chronic constipation, in which 200 eligible volunteers with chronic constipation will be randomly assigned to a probiotic group (oral Lactobacillus plantarum P9 probiotic powder, 100 billion colony-forming units (CFUs)/day) or a placebo group. Volunteers, treatment distributors, data collectors, and data analysts will be blinded. The primary outcome is the weekly mean frequency of complete spontaneous bowel movements (CSBMs), and secondary outcomes include weekly mean frequency of CSBMs ≥3, weekly mean frequency of spontaneous bowel movements (SBMs), weekly mean stool appearance score, weekly mean difficulty of passing stool score, weekly percentage of volunteers who use auxiliary measures to assist with defecation (WPUAMA), quality-of-life (QOL) score, emotional status score, gut microbiome, and faecal metabolome. Each outcome measure will be assessed at the time points of preadministration (day 0), administration (day 14 and/or 28), and postadministration (day 42) to identify inter- and intragroup differences. Adverse events will be recorded to evaluate the safety of L. plantarum P9. Discussion. The protocol will provide methodological guidance for other similar studies, avoiding methodological bias and ultimately facilitating the formulation of consensus on the use of probiotics as a constipation-relieving agent. In addition, the results are more comprehensive than those of existing studies and may objectively and scientifically reflect the effectiveness of L. plantarum P9 on constipation. If the expected study findings are obtained, L. plantarum P9, taken as a probiotic, may become a complementary choice for chronically constipated patients. This trial is registered with Chinese Clinical Trial Registry (ChiCTR) (no. ChiCTR2000038396) registered on November 22, 2020, https://www.chictr.org.cn/showproj.aspx?proj=54024.
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Zhang S, Wang R, Li D, Zhao L, Zhu L. Role of gut microbiota in functional constipation. Gastroenterol Rep (Oxf) 2021; 9:392-401. [PMID: 34733524 PMCID: PMC8560038 DOI: 10.1093/gastro/goab035] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 05/06/2021] [Accepted: 07/18/2021] [Indexed: 12/19/2022] Open
Abstract
Functional constipation (FC) is common, yet the etiology is not clear. Accumulating evidence suggests an association between FC and abnormal gut microbiota. The relationship between the gut microbiota and the gut transit is likely bidirectional. This review summarizes the current evidence regarding the impact of gut microbiota on the pathogenesis of FC. By modulating the colonic motility, secretion, and absorption, gut microbiota may contribute to the development of FC through microbial metabolic activities involving bile acids, short-chain fatty acids, 5-hydroxytryptamine, and methane. In support of the key roles of the gut microbiota in FC, treatment with probiotics, prebiotics, synbiotics, and traditional Chinese medicine often result in compositional and functional changes in the gut microbiota. Further studies on the pathogenesis of FC and the therapeutic mechanism of microecological agents will provide a knowledge base for better management of FC.
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Affiliation(s)
- Shengsheng Zhang
- Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, P. R. China
| | - Ruixin Wang
- Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, P. R. China
| | - Danyan Li
- Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, P. R. China
| | - Luqing Zhao
- Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, P. R. China
| | - Lixin Zhu
- Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Zhang Q, Zhong D, Sun R, Zhang Y, Pegg RB, Zhong G. Prevention of loperamide induced constipation in mice by KGM and the mechanisms of different gastrointestinal tract microbiota regulation. Carbohydr Polym 2020; 256:117418. [PMID: 33483010 DOI: 10.1016/j.carbpol.2020.117418] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 11/02/2020] [Accepted: 11/16/2020] [Indexed: 12/18/2022]
Abstract
Constipation is one of the most prevalent gastrointestinal tract diseases. Konjac glucomannan (KGM) dietotherapy can effectively relieve the clinical symptoms of patients with constipation. However, the causal relationship among KGM, constipation and different gastrointestinal microbiome (i.e., the stomach {St}, small intestine {S}, and large intestine {L}) remains poorly understood. In this study, constipated mice were treated with KGM (75, 150, 300 mg/kg bw). Results showed that KGM treatment improved the general physiological state, fecal character, small intestinal propulsive rate, gastric emptying rate, MTL and AchE activities, ET-1, 5-HT, and NO levels, and SCFA concentrations. KGM in the diets of constipated mice reduced the diversity of St and S microbiota, while increased those in the L. The KGM intervention regulated the microbiota profile, which afterwards was closer to the normal mouse group: confirmation was provided by different changes of bacteria like Lactobacillus, Bifidobacterium and Allobaculum spp et al.
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Affiliation(s)
- Qi Zhang
- College of Food Science, Southwest University, Chongqing, 400715, China
| | - Dian Zhong
- Department of Food Science and Technology, University of Georgia, Athens, 30602, United States
| | - Rui Sun
- College of Food Science, Southwest University, Chongqing, 400715, China
| | - Yang Zhang
- College of Food Science, Southwest University, Chongqing, 400715, China
| | - Ronald B Pegg
- Department of Food Science and Technology, University of Georgia, Athens, 30602, United States.
| | - Geng Zhong
- College of Food Science, Southwest University, Chongqing, 400715, China.
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Talebi S, Karimifar M, Heidari Z, Mohammadi H, Asbaghi O, Hadi A, Marx W, Askari G. The effect of synbiotic supplementation on anthropometric indices, appetite, and constipation in people with hypothyroidism: A randomized, double-blind, placebo-controlled trial. Phytother Res 2020; 34:2712-2720. [PMID: 32363616 DOI: 10.1002/ptr.6710] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 04/02/2020] [Accepted: 04/10/2020] [Indexed: 12/25/2022]
Abstract
Hypothyroidism and obesity are two highly prevalent conditions that appear to be closely related. Hypothyroidism is correlated with weight gain, loss of appetite, constipation, and a higher incidence of obesity. The present study aimed to investigate the effects of synbiotic supplementation on anthropometric indices, appetite, and constipation in subjects with hypothyroidism. Sixty subjects with hypothyroidism were assigned into two groups to receive either 500 mg/day of synbiotic (n = 30) or a placebo (n = 30) per day for 8 weeks. Anthropometric indices, appetite, and constipation were assessed at study baseline and end of the trial. At the end of trial, waist-to-hip ratio was significantly decreased in the synbiotic group (p = .030), whereas there were no significant differences between groups. We did not observe any statistically significant change in appetite or other anthropometric indices (p > .05). Compared with the placebo synbiotic supplementation led to a significant reduction in constipation (p = .048). The results of the present trial indicated that synbiotic supplementation may have favorable results in constipation among subjects with hypothyroidism for 8 weeks. Further studies with larger sample size and longer duration are needed to confirm our findings.
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Affiliation(s)
- Sepide Talebi
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.,Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mozhgan Karimifar
- Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zahra Heidari
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamed Mohammadi
- Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Omid Asbaghi
- Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Amir Hadi
- Halal Research Center of IRI, FDA, Tehran, Iran
| | - Wolfgang Marx
- iMPACT, School of Medicine, Deakin University, Melbourne, Victoria, Australia
| | - Gholamreza Askari
- Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
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12
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Brusciano L, Gualtieri G, Gambardella C, Terracciano G, Tolone S, Del Genio G, Lucido FS, Docimo L. Pelvic floor dyssynergia: the new iceberg syndrome. Tech Coloproctol 2020; 24:393-394. [PMID: 32112246 DOI: 10.1007/s10151-020-02164-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 02/06/2020] [Indexed: 11/29/2022]
Affiliation(s)
- L Brusciano
- U.O.C General and Obesity Surgery, University of Study of Campania "Luigi Vanvitelli" Naples, Naples, Italy.
| | - G Gualtieri
- U.O.C General and Obesity Surgery, University of Study of Campania "Luigi Vanvitelli" Naples, Naples, Italy
| | - C Gambardella
- U.O.C General and Obesity Surgery, University of Study of Campania "Luigi Vanvitelli" Naples, Naples, Italy.,Department of Cardiothoracic Sciences, School of Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - G Terracciano
- U.O.C General and Obesity Surgery, University of Study of Campania "Luigi Vanvitelli" Naples, Naples, Italy
| | - S Tolone
- U.O.C General and Obesity Surgery, University of Study of Campania "Luigi Vanvitelli" Naples, Naples, Italy
| | - G Del Genio
- U.O.C General and Obesity Surgery, University of Study of Campania "Luigi Vanvitelli" Naples, Naples, Italy
| | - F S Lucido
- U.O.C General and Obesity Surgery, University of Study of Campania "Luigi Vanvitelli" Naples, Naples, Italy
| | - L Docimo
- U.O.C General and Obesity Surgery, University of Study of Campania "Luigi Vanvitelli" Naples, Naples, Italy
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13
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Valentini Neto J, Chella TP, Rudnik DP, Ribeiro SML. EFFECTS OF SYNBIOTIC SUPPLEMENTATION ON GUT FUNCTIONING AND SYSTEMIC INFLAMMATION OF COMMUNITY-DWELLING ELDERS - SECONDARY ANALYSES FROM A RANDOMIZED CLINICAL TRIAL. ARQUIVOS DE GASTROENTEROLOGIA 2020; 57:24-30. [PMID: 32294732 DOI: 10.1590/s0004-2803.202000000-06] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 10/27/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Aging is a complex process marked by alterations on gut functioning and physiology, accompanied by an increase on the inflammatory status, leading to a scenario called "inflammaging". OBJECTIVE To evaluate the effects of a synbiotic substance on systemic inflammation, gut functioning of community-dwelling elders. METHODS This is a secondary analysis from a randomized clinical trial, lasting 24 weeks, including 49 elders, distributed into two groups: SYN (n=25), which received a synbiotic substance (Frutooligossacaride 6g, Lactobacillus paracasei LPC-31 109 to 108 UFC, Lactobacillus rhamnosus HN001 109 to 108 UFC, Lactobacillus acidophilus NCFM 109 to 108 UFC e Bifidobacterium lactis HN019 109 to 108 UFC), or PLA (n=24), receiving placebo. The evaluations consisted of serum IL-10 e TNF-α (after overnight fasting), evaluation of chronic constipation (by Rome III Criteria) and faeces types (by Bristol Stool Form Scale). Data were compared before and after the supplementation time, and between groups. RESULTS No significant differences were found between baseline and final values of serum inflammatory markers. Some subtle beneficial changes were observed in SYN, concerning both gut functioning and faeces types. CONCLUSION From our data, synbiotic supplementation showed a subtle benefit in gut functioning in apparently healthy community-dwelling elders. Our findings can suggest that the benefits in healthy individuals were less expressive than the ones presented in studies with individuals previously diagnosed as dysbiosis. Future studies, comparing elders with and without gut dysbiosis can confirm our findings.
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Affiliation(s)
- João Valentini Neto
- Universidade de São Paulo, Faculdade de Saúde Pública, Departamento de Nutrição, São Paulo, SP, Brasil
| | - Terezinha Perricci Chella
- Universidade de São Paulo, Faculdade de Saúde Pública, Departamento de Nutrição, São Paulo, SP, Brasil
| | - Danielle Panipucci Rudnik
- Universidade de São Paulo, Faculdade de Saúde Pública, Departamento de Nutrição, São Paulo, SP, Brasil
| | - Sandra Maria Lima Ribeiro
- Universidade de São Paulo, Faculdade de Saúde Pública, Departamento de Nutrição, São Paulo, SP, Brasil
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Ohkusa T, Koido S, Nishikawa Y, Sato N. Gut Microbiota and Chronic Constipation: A Review and Update. Front Med (Lausanne) 2019; 6:19. [PMID: 30809523 PMCID: PMC6379309 DOI: 10.3389/fmed.2019.00019] [Citation(s) in RCA: 212] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 01/21/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Chronic constipation, including functional constipation and constipation-type irritable bowel syndrome, is a prevalent, multifactorial gastrointestinal disorder, and its etiology and pathophysiology remain poorly understood. Recently studies using 16S rRNA-based microbiota profiling have demonstrated dysbiosis of gut microbiota in chronic constipation. Aims: To provide an overview of recent studies for microbiota in chronic constipation and treatments for chronic constipation using probiotics, prebiotics, synbiotics, antibiotics and fecal microbiota transplantation (FMT). Methods: PubMed searches were performed up to 1 August 2018 using keywords: “IBS,” “IBS-C,” “irritable bowel syndrome,” “irritable bowel syndrome with constipation,” “functional constipation,” “chronic constipation” in combination with “gut microbiota,” “dysbiosis,” “gut microflora” for microbiota in chronic constipation, and in combination with “probiotics,” “prebiotics,” “synbiotics,” “antibiotics,” and “fecal microbiota transplantation.” Results: The findings of gut microbiota in functional constipation are inconsistent, and currently no consensus exists. Although no clear consensus exists, compared with healthy subjects, IBS-C patients have a lower level of Actinobacteria, including Bifidobacteria, in their fecal samples and a higher level of Bacteroidetes in their mucosa. In most randomized controlled and parallel-group trials, probiotics, prebiotics, synbiotics, antibiotics, and FMT therapy for chronic constipation were effective with few side effects. However, there are many studies in a small number and the types of probiotics are different, it is difficult to evaluate the effect. Conclusions: Evidence indicates that dysbiosis of gut microbiota may contribute to functional constipation and constipation-type irritable bowel syndrome. Targeting treatments for the dysbiosis of constipation by probiotics, prebiotics, synbiotics, antibiotics, and FMT may be a new option, especially for refractory constipation to conventional therapies.
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Affiliation(s)
- Toshifumi Ohkusa
- Department of Microbiota Research, Juntendo University Graduate School of Medicine, Tokyo, Japan.,Department of Gastroenterology and Hepatology, The Jikei University Kashiwa Hospital, Kashiwa, Japan
| | - Shigeo Koido
- Department of Gastroenterology and Hepatology, The Jikei University Kashiwa Hospital, Kashiwa, Japan
| | - Yuriko Nishikawa
- Department of Microbiota Research, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Nobuhiro Sato
- Department of Microbiota Research, Juntendo University Graduate School of Medicine, Tokyo, Japan
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15
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Zheng H, Chen Q, Chen M, Wu X, She TW, Li J, Huang DQ, Yue L, Fang JQ. Nonpharmacological conservative treatments for chronic functional constipation: A systematic review and network meta-analysis. Neurogastroenterol Motil 2019; 31:e13441. [PMID: 30125427 DOI: 10.1111/nmo.13441] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Revised: 06/12/2018] [Accepted: 07/06/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Patients with functional chronic constipation (CFC) often select nonpharmacological treatments. We aimed to examine the comparative effectiveness of nonpharmacological conservative treatments in treating CFC. METHODS We searched MEDLINE, EMBASE, Cochrane library, CINAHL, AMED, ISI web of knowledge, and conference proceedings from January 2000 to June 2016. Randomized controlled trials comparing nonpharmacological conservative treatments with placebo, sham interventions, or conventional treatments were included. Nonpharmacological conservative treatments were defined as interventions without involvement of medication or surgery. We extracted trial data in duplicate and assessed the risk of bias. We pooled continuous data using standard mean differences (SMDs) and binary data using risk ratios (RRs), and we provided their 95% confidence intervals. KEY RESULTS We included 33 trials (4324 participants and 8 nonpharmacological treatments). Compared with placebo interventions, TENS (SMD 1.60, 95% CI 0.28-2.92), probiotic (SMD 1.40, 95% CI 0.94-1.86), and acupuncture (SMD 1.00, 95% CI 0.39-1.60) had significantly larger effect on stool frequency; acupuncture (RR 1.56, 95% CI 1.14-2.14) had significantly higher responder rate; and moxibustion (SMD 2.50, 95% CI 0.05-4.95) had significant larger effect on Bristol score. Compared with laxative, acupuncture had significantly larger effect on stool frequency (RR 2.01, 95% CI 1.16-3.49) and had lower rate of adverse events (RR 0.38, 95% CI 0.18-0.80). CONCLUSIONS TENS and acupuncture relatively ranked the best in managing CFC, but the results should be interpreted with caution due to small study effects. Registration number: PROSPERO CRD42014006686.
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Affiliation(s)
- Hui Zheng
- School of Acupuncture and Tuina, The Third Teaching Hospital, Institute of Acupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qin Chen
- The Third Clinical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Min Chen
- Clinical College, Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xi Wu
- School of Acupuncture and Tuina, The Third Teaching Hospital, Institute of Acupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Tian-Wei She
- School of Acupuncture and Tuina, The Third Teaching Hospital, Institute of Acupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Juan Li
- School of Acupuncture and Tuina, The Third Teaching Hospital, Institute of Acupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - De-Quan Huang
- Clinical College, Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ling Yue
- School of Acupuncture and Tuina, The Third Teaching Hospital, Institute of Acupuncture and Homeostasis Regulation, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jian-Qiao Fang
- The Third Clinical College, Zhejiang Chinese Medical University, Hangzhou, China
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16
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Effects of Synbiotics among Constipated Adults in Serdang, Selangor, Malaysia-A Randomised, Double-Blind, Placebo-Controlled Trial. Nutrients 2018; 10:nu10070824. [PMID: 29949873 PMCID: PMC6073678 DOI: 10.3390/nu10070824] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 06/17/2018] [Accepted: 06/22/2018] [Indexed: 12/12/2022] Open
Abstract
Synbiotics approach complementarily and synergistically toward the balance of gastrointestinal microbiota and improvement in bowel functions. A randomised, double-blind, placebo-controlled study was conducted to examine the effects of a synbiotics supplement among constipated adults. A total of 85 constipated adults, diagnosed by Rome III criteria for functional constipation were randomised to receive either synbiotics (n = 43) or placebo (n = 42) once daily (2.5 g) in the morning for 12 weeks. Eight times of follow-up was conducted every fortnightly with treatment response based on a questionnaire that included a record of evacuation (stool frequency, stool type according to Bristol Stool Form Scale), Patients Assessment on Constipation Symptoms (PAC-SYM), and Patients Assessment on Constipation Quality of Life (PAC-QOL). There were no significant differences in stool evacuation, but defecation frequency and stool type in treatment group were improved tremendously than in placebo group. While the treatment group was reported to have higher reduction in severity of functional constipation symptoms, the differences were not statistically significant. Dietary supplementation of synbiotics in this study suggested that the combination of probiotics and prebiotics improved the functional constipation symptoms and quality of life although not significant. This was due to the high placebo effect which synbiotics failed to demonstrate benefit over the controls.
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17
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Analysis of fecal microbiota in patients with functional constipation undergoing treatment with synbiotics. Eur J Clin Microbiol Infect Dis 2018; 37:555-563. [DOI: 10.1007/s10096-017-3149-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Accepted: 11/22/2017] [Indexed: 02/08/2023]
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18
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Postoperative symbiotic in patients with head and neck cancer: a double-blind randomised trial. Br J Nutr 2017; 119:190-195. [PMID: 29277158 DOI: 10.1017/s0007114517003403] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Studies on the 'gut origin of sepsis' have suggested that stressful insults, such as surgery, can affect intestinal permeability, leading to bacterial translocation. Symbiotics have been reported to be able to improve gut permeability and modulate the immunologic system, thereby decreasing postoperative complications. Therefore we aimed to evaluate the postoperative use of symbiotics in head and neck cancer surgical patients for intestinal function and permeability, as well as the postoperative outcomes. Patients were double-blind randomised into the symbiotic (n 18) or the control group (n 18). Samples were administered twice a day by nasoenteric tube, starting on the 1st postoperative day until the 5th to 7th day, and comprised 109 colony-forming units/ml each of Lactobacillus paracasei, L. rhamnosus, L. acidophilus, and Bifidobacterium lactis plus 6 g of fructo-oligosaccharides, or a placebo (6 g of maltodextrin). Intestinal function (day of first evacuation, total stool episodes, stool consistency, gastrointestinal tract symptoms and gut permeability by diamine oxidase (DAO) enzyme) and postoperative complications (infectious and non-infectious) were assessed. Results of comparison of the pre- and postoperative periods showed that the groups were similar for all outcome variables. In all, twelve patients had complications in the symbiotic group v. nine in the control group (P>0·05), and the preoperative-postoperative DAO activity ranged from 28·5 (sd 15·4) to 32·7 (sd 11·0) ng/ml in the symbiotic group and 35·2 (sd 17·7) to 34·1 (sd 12·0) ng/ml in the control group (P>0·05). In conclusion, postoperative symbiotics did not impact on intestinal function and postoperative outcomes of head and neck surgical patients.
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Miller LE, Ouwehand AC, Ibarra A. Effects of probiotic-containing products on stool frequency and intestinal transit in constipated adults: systematic review and meta-analysis of randomized controlled trials. Ann Gastroenterol 2017; 30:629-639. [PMID: 29118557 PMCID: PMC5670282 DOI: 10.20524/aog.2017.0192] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 08/24/2017] [Indexed: 12/12/2022] Open
Abstract
Background: Probiotics are commonly recommended for the alleviation of constipation symptoms. The aim of this research was to determine the effects of probiotic-containing products on stool frequency and intestinal transit time (ITT) in constipated adults and to determine the factors that influence the efficacy of these products. Methods: We conducted a systematic review of randomized controlled trials that measured weekly stool frequency or ITT in constipated adults receiving probiotic-containing supplements. A random effects meta-analysis was performed; stool frequency was summarized by the mean difference statistic and ITT was summarized by the standardized mean difference (SMD) statistic. Meta-regression and diagnostic model performance testing were used to identify publication bias and sources of heterogeneity. Results: A total of 21 studies (23 comparisons) comprising 2656 subjects were included. All studies utilized probiotics containing Lactobacillus or Bifidobacterium species. Probiotic-containing products resulted in a mean increase in weekly stool frequency of 0.83 (95% confidence interval [CI] 0.53-1.14, P<0.001). There was high heterogeneity among the studies (I2=85%, P<0.001) and evidence of significant publication bias (Egger’s P-value <0.01). After adjustment for publication bias, the mean difference in weekly stool frequency was reduced from 0.83 to 0.30. The effects on stool frequency were greater in studies where functional constipation was diagnosed using Rome III (P<0.01), or Rome II or III criteria (P<0.05), compared to non-Rome diagnosis techniques. Probiotic-containing products were also efficacious in reducing ITT (SMD=0.65, 95%CI 0.33-0.97, P<0.001). There was high heterogeneity among studies (I2=66%, P<0.01), but no evidence of publication bias (Egger’s P-value=0.52). A larger total sample size was associated with greater efficacy as regards ITT (P=0.03). The probiotic species, the number of probiotic strains and the daily probiotic dosage had no influence on the outcomes. Conclusion: Supplementation with products containing Lactobacillus or Bifidobacterium species increases stool frequency and reduces ITT in constipated adults. However, since significant heterogeneity in outcomes was detected among the studies analyzed, the results should be interpreted with caution.
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Affiliation(s)
- Larry E Miller
- Miller Scientific Consulting, Inc., Asheville, NC, United States (Larry E. Miller)
| | - Arthur C Ouwehand
- DuPont Nutrition and Health, Kantvik, Finland (Arthur C. Ouwehand, Alvin Ibarra)
| | - Alvin Ibarra
- DuPont Nutrition and Health, Kantvik, Finland (Arthur C. Ouwehand, Alvin Ibarra)
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20
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Miller LE, Ibarra A, Ouwehand AC. Normative Values for Colonic Transit Time and Patient Assessment of Constipation in Adults With Functional Constipation: Systematic Review With Meta-Analysis. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2017; 11:1179552217729343. [PMID: 28894394 PMCID: PMC5582663 DOI: 10.1177/1179552217729343] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 08/01/2017] [Indexed: 12/16/2022]
Abstract
Availability of normative patient outcome data may assist in designing experiments and estimating sample sizes. The purpose of this review was to determine normative ranges for colonic transit time (CTT), Patient Assessment of Constipation-Symptoms (PAC-SYM), and Patient Assessment of Constipation-Quality of Life (PAC-QOL) in adults diagnosed with functional constipation per Rome III guidelines. Pooled estimates were derived from random-effects meta-analysis. Meta-regression was used to explore sources of heterogeneity among studies. A total of 24 studies (3786 patients) were included in the review. In 10 studies with 1119 patients, pooled CTT was 58 hours (95% confidence interval [CI]: 50-65 hours). Publication bias was not evident (Egger P = .51); heterogeneity was high (I2 = 92%, P < .001). In meta-regression, geographical location explained 57% of the between-study variance, with CTT significantly longer in studies conducted in Europe (71 hours) compared with Asia (49 hours) or the Americas (44 hours). In 9 studies with 2061 patients, pooled PAC-SYM was 1.70 (95% CI: 1.58-1.83). Publication bias was not evident (Egger P = .44). Heterogeneity was high (I2 = 90%, P < .001); however, no study or patient factor influenced PAC-SYM in meta-regression. In 12 studies with 1805 patients, pooled PAC-QOL was 1.97 (95% CI: 1.70-2.24). Publication bias was not evident (Egger P = .28); heterogeneity was high (I2 = 98%, P < .001). In meta-regression, age explained 52% of the between-study variance, with older age associated with lower PAC-QOL scores. Overall, in adults diagnosed with functional constipation per Rome III criteria, significant heterogeneity in CTT, PAC-SYM, and PAC-QOL exists among studies. Variability among studies may be explained by geography and patient factors.
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Affiliation(s)
| | - Alvin Ibarra
- Global Health and Nutrition Sciences, DuPont Nutrition & Health, Kantvik, Finland
| | - Arthur C Ouwehand
- Global Health and Nutrition Sciences, DuPont Nutrition & Health, Kantvik, Finland
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Li T, Lu X, Yang X. Evaluation of clinical safety and beneficial effects of stachyose-enriched α-galacto-oligosaccharides on gut microbiota and bowel function in humans. Food Funct 2017; 8:262-269. [DOI: 10.1039/c6fo01290f] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
This is the first study providing clinical bases for developing DSG as a novel and safe agent against functional constipation.
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Affiliation(s)
- Ting Li
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control
- College of Food Engineering and Nutritional Science
- Shaanxi Normal University
- Xi'an 710062
- China
| | - Xinshan Lu
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control
- College of Food Engineering and Nutritional Science
- Shaanxi Normal University
- Xi'an 710062
- China
| | - Xingbin Yang
- Shaanxi Engineering Laboratory for Food Green Processing and Safety Control
- College of Food Engineering and Nutritional Science
- Shaanxi Normal University
- Xi'an 710062
- China
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Yu T, Zheng YP, Tan JC, Xiong WJ, Wang Y, Lin L. Effects of Prebiotics and Synbiotics on Functional Constipation. Am J Med Sci 2016; 353:282-292. [PMID: 28262216 DOI: 10.1016/j.amjms.2016.09.014] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Revised: 07/26/2016] [Accepted: 09/30/2016] [Indexed: 02/08/2023]
Abstract
The objective was to determine the effects of prebiotics and synbiotics on adults with functional constipation (FC). Medline, Embase and the Cochrane Library were searched for literature published up to February 2015. We selected randomized controlled trials (RCTs) that reported administration of prebiotics or synbiotics to adults with FC. The end points included stool frequency, stool consistency and other symptoms related to constipation. Mean differences (MD) or standard mean differences (SMD) were used for continuous outcomes and risk ratios for discontinuous outcomes using a random-effects model. The Cochrane Risk of Bias Tool was used to determine the quality of the trials. Funnel plots and Egger's test were used to analyze for publication bias. We included 5 RCTs involving 199 patients who were administered prebiotics and 8 RCTs involving 825 patients who were administered synbiotics. Prebiotics increased weekly stool frequency (MD: 1.01bowel movements/week, 95% CI: 0.04-1.99) and improved stool consistency (SMD: -0.59, 95% CI: -1.16 to -0.02). Subgroup analysis showed specific effects for galacto-oligosaccharides on stool frequency, consistency, ease of defecation and abdominal pain. Synbiotics significantly improved stool frequency (MD: 1.15bowel movements/week, 95% CI: 0.58-1.71), consistency (SMD: 0.63, 95% CI: 0.33-0.92) and reduced whole-gut transit time (MD: 13.52, 95% CI: -26.56 to -0.49) in patients with FC. Subgroup analysis showed specific effects for fructo-oligosaccharides and probiotic combinations on stool frequency, consistency, straining defecation and bloating. Galacto-oligosaccharides and synbiotics made up of fructo-oligosaccharides with probiotic combinations may improve stool frequency, consistency and some other symptoms related to constipation.
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Affiliation(s)
- Ting Yu
- Department of Gastroenterology, The First Affiliated Hospital, Nanjing Medical University, Nanjing , Jiangsu Province, China
| | - Yong-Ping Zheng
- Department of Gastroenterology, The First Affiliated Hospital, Nanjing Medical University, Nanjing , Jiangsu Province, China
| | - Jia-Cheng Tan
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu Province, China
| | - Wen-Jie Xiong
- Department of Gastroenterology, The First Affiliated Hospital, Nanjing Medical University, Nanjing , Jiangsu Province, China
| | - Yun Wang
- Department of Gastroenterology, The First Affiliated Hospital, Nanjing Medical University, Nanjing , Jiangsu Province, China
| | - Lin Lin
- Department of Gastroenterology, The First Affiliated Hospital, Nanjing Medical University, Nanjing , Jiangsu Province, China.
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Campanini A, De Conto U, Cavasin F, Bastiani F, Camarotto A, Gardini L, Geremia A, Marastoni C, Missorini C, Quarantelli E, Sassi U, Scarabello F, Dal Bo N, Riccò M, Grillo S, Landi S, Di Mario F. A Primary-Care Interventional Model on the Diverticular Disease: Searching for the Optimal Therapeutic Schedule. J Clin Gastroenterol 2016; 50 Suppl 1:S93-S96. [PMID: 27622379 DOI: 10.1097/mcg.0000000000000670] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION In routine colonoscopy, diverticulosis is the most commonly found feature, but only a minority of these cases show symptoms of diverticular disease.From June 2014 to December 2014, we enrolled prospectively 178 patients affected by symptomatic uncomplicated diverticular disease (Male/Female=0.47, mean age 71.7±11.5 y, range 41 to 95 y) from 15 General Pratictioners patient files. All patients were symptomatic; in all cases, diagnosis was been confirmed by a colonoscopy performed at least 1 year before. Patients with acute diverticulitis were excluded.On the basis of the predominant symptoms (abdominal complaints or constipation), patients were addressed to 4 different therapeutic approaches using mesalamine, rifaximine, probiotics (in a consortium of different species of Lactobacillus and Bifidobacterium), and fibers (Plantago Ovata Husk). All treatments lasted 3 months. RESULTS Sixty-three patients were enrolled in group A (rifaximine), 43 in group A1 (rifaximine+fibers+probiotics), 23 in group B (mesalamine), and 31 in group B1 (mesalamine+fibers).Analysis of variance suggested a statistically significant difference (P<0.003) among groups at the end of the observation period, with Groups A1 and B1 showing a higher number of bowel movement per week. Global linear measurement confirmed the role of treatment as a significant factor (F=2.858; P=0.039) associated with body mass index (F=6.972; P<0.009). CONCLUSIONS In accordance with the baseline clinical presentation, the supplementation of fiber and/or probiotics is associated with a statistically significant improvement in the clinical pattern of symptoms in patients with diverticular disease in a primary-care/family physician setting.
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Affiliation(s)
- Angelo Campanini
- *Public Health Service, AUSL Parma ¶Department of Clinical and Experimental Medicine, University of Parma, Parma †Public Health Service, AUSL Treviso ‡Gastroenterological Unit, Treviso Hospital, Treviso §Department of Prevention, Occupational Health and Safety Unit ∥Provincial Agency for Health Services of the Autonomous Province of Trento, Trento, Italy
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Miller LE, Zimmermann AK, Ouwehand AC. Contemporary meta-analysis of short-term probiotic consumption on gastrointestinal transit. World J Gastroenterol 2016; 22:5122-5131. [PMID: 27275105 PMCID: PMC4886388 DOI: 10.3748/wjg.v22.i21.5122] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Revised: 02/09/2016] [Accepted: 03/02/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) in adults and to identify factors that influence these outcomes.
METHODS: We conducted a systematic review of randomized controlled trials of probiotic supplementation that measured ITT in adults. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses examined the impact of moderator variables on SMD of ITT.
RESULTS: A total of 15 clinical trials with 17 treatment effects representing 675 subjects were included in this analysis. Probiotic supplementation was moderately efficacious in decreasing ITT compared to control, with an SMD of 0.38 (95%CI: 0.23-0.53, P < 0.001). Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation (SMD: 0.57 vs 0.22, P < 0.01) and in studies with high vs low study quality (SMD: 0.45 vs 0.00, P = 0.01). Constipation (R2 = 38%, P < 0.01), higher study quality (R2 = 31%, P = 0.01), older age (R2 = 27%, P = 0.02), higher percentage of female subjects (R2 = 26%, P = 0.02), and fewer probiotic strains (R2 = 20%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Medium to large treatment effects were identified with B. lactis HN019 (SMD: 0.67, P < 0.001) and B. lactis DN-173 010 (SMD: 0.54, P < 0.01) while other probiotic strains yielded negligible reductions in ITT relative to control.
CONCLUSION: Probiotic supplementation is moderately efficacious for reducing ITT in adults. Probiotics were most efficacious in constipated subjects, when evaluated in high-quality studies, and with certain probiotic strains.
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