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Pell LG, Qamar H, Bassani DG, Heasley C, Funk C, Chen CY, Shawon J, O'Callaghan KM, Pullenayegum E, Hamer DH, Haque R, Kabir M, Ahmed T, O'Kelly C, Hossain MI, Khan AZ, Loutet MG, Islam MS, Morris SK, Shah PS, Sherman PM, Sultana S, Mahmud AA, Saha SK, Sarker SA, Roth DE. Neonatal administration of Lactiplantibacillus plantarum ATCC 202195 with or without fructooligosaccharide in Bangladesh: a placebo-controlled randomized trial. mSphere 2025; 10:e0103224. [PMID: 39992135 PMCID: PMC11934310 DOI: 10.1128/msphere.01032-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 01/22/2025] [Indexed: 02/25/2025] Open
Abstract
Lactiplantibacillus plantarum ATCC 202195 (LP202195) plus fructooligosaccharide (FOS) for 7 days was previously shown to colonize the infant intestine up to 6 months of age and reduced sepsis rates among young infants in rural India. In a phase 2 randomized controlled trial in Dhaka, Bangladesh (N = 519), neonatal administration of LP202195 for 1 or 7 days, with or without FOS, increased LP202195 stool abundance from 14 to 60 days of age, versus placebo. Abundance progressively declined in the post-administration period and did not persist beyond 2 months of age. FOS did not affect LP202195 abundance or its duration of persistence. All regimens were well-tolerated and safe. The absence of LP202195 colonization was inconsistent with results from a prior trial. Additional large-scale trials of LP202195 ± FOS are needed to establish its efficacy in infants who do not become LP202195-colonized. IMPORTANCE Among infants born in Dhaka, Bangladesh, a 7-day regimen of Lactiplantibacillus plantarum ATCC 202195 (LP202195) plus fructooligosaccharide (FOS) did not colonize the infant gastrointestinal (GI) tract. The absence of colonization is inconsistent with a prior study of the same synbiotic regimen in India, in which LP202195 was shown to persist in the infant GI tract for up to 6 months. Sustained LP202195 colonization was thought to be required for the probiotic to impart its beneficial impact on newborn sepsis. Therefore, additional trials are warranted to confirm the previously observed effects of LP202195 on infant clinical outcomes in the absence of LP202195 colonization. Moreover, since regimens of LP202195 that did not include FOS were indistinguishable from the synbiotic in terms of colonization, safety, and tolerability, future trials should assess the role of FOS for clinical efficacy; removing FOS would reduce costs, an important consideration for scale-up. CLINICAL TRIALS This study has been registered at ClinicalTrials.gov as NCT05180201.
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Affiliation(s)
- Lisa G. Pell
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Huma Qamar
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Diego G. Bassani
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, Hospital for Sick Children, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Cole Heasley
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Celine Funk
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Chun-Yuan Chen
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Jakaria Shawon
- Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Karen M. O'Callaghan
- Department of Nutritional Sciences, King’s College London, London, United Kingdom
| | - Eleanor Pullenayegum
- Child Health Evaluative Sciences, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Davidson H. Hamer
- Department of Global Health, Boston University School of Public Health and Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA
| | - Rashidul Haque
- Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Mamun Kabir
- Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Tahmeed Ahmed
- Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Ciobha O'Kelly
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Md Iqbal Hossain
- Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Afreen Z. Khan
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Miranda G. Loutet
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
| | | | - Shaun K. Morris
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Prakesh S. Shah
- Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Department of Pediatrics, Mt. Sinai Hospital, Toronto, Ontario, Canada
| | - Philip M. Sherman
- Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
- Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Shamima Sultana
- Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Abdullah Al Mahmud
- Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | | | - Shafiqul A. Sarker
- Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh
| | - Daniel E. Roth
- Centre for Global Child Health, Hospital for Sick Children, Toronto, Ontario, Canada
- Child Health Evaluative Sciences, Hospital for Sick Children, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Department of Paediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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Lenoir M, Wienke J, Fardao-Beyler F, Roese N. An 8-Week Course of Bifidobacterium longum 35624 ® Is Associated with a Reduction in the Symptoms of Irritable Bowel Syndrome. Probiotics Antimicrob Proteins 2025; 17:315-327. [PMID: 37702965 PMCID: PMC11832793 DOI: 10.1007/s12602-023-10151-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] [Subscribe] [Scholar Register] [Accepted: 08/22/2023] [Indexed: 09/14/2023]
Abstract
Irritable bowel syndrome (IBS) is one of the disorders most frequently diagnosed by gastroenterologists. Probiotics are promising tools for the management of IBS. The objective of the present study was to evaluate the effectiveness and tolerability of a probiotic (Bifidobacterium longum 35624®) in adults (aged 18 or over) with IBS (as defined by the Rome IV criteria). In an open-label, observational, post-market study conducted in Germany, adults with IBS and a prior recommendation for the intake of B. longum 35624® were recruited by family physicians. During the 8-week course of treatment, the study participants filled out a weekly questionnaire that enabled calculation of a total IBS symptom score (TISS, the sum of abdominal pain, bloating, passage of gas, constipation, and diarrhea individual symptom scores) and the well-known IBS severity scoring system (IBS-SSS) score. Thirty-seven patients were included. The course of B. longum 35624® was associated with a significant reduction (43.4%) in the TISS vs. baseline. The mean individual symptom grades for passage of gas and bloating fell significantly from "moderate" at baseline to "very mild to mild" after 8 weeks of treatment, whereas those for abdominal pain and diarrhea fell significantly from "mild to moderate" to "very mild to mild." Over 60% of the participants achieved clinically meaningful reductions in the TISS (> 30%) and the IBS-SSS score (> 50 points). The effectiveness of B. longum 35624® was rated as "good to satisfactory" by study participants and the investigating physicians. One mild adverse event (nausea) was potentially linked to the study treatment. We conclude that an 8-week course of B. longum 35624® was associated with significant, clinically meaningful symptom relief in a typical population of adult patients with IBS.
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Affiliation(s)
- Marion Lenoir
- Biocodex SAS, 7 Avenue Gallieni, F-94257, Gentilly, France
| | - Jörg Wienke
- , Ritastrasse 2, D-40589 Düsseldorf, Germany
| | | | - Nadine Roese
- MEDICE Arzneimittel Pütter GmbH & Co. KG, Kuhloweg 37, D-58638, Iserlohn, Germany
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3
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Molino S, Lerma-Aguilera A, Piskorz MM, López Mingorance F, Montero JM, Uehara T, Hashimoto H, González Ballerga E, Olmos JA. Tannin-based supplementation influences gut microbiota composition and activity in IBS-D patients with a potential impact on symptoms: a pilot study. Food Funct 2024; 15:8893-8903. [PMID: 39129514 DOI: 10.1039/d4fo02236j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/13/2024]
Abstract
As the involvement of the intestinal microbiota in the etiopathology of irritable bowel syndrome, subtype diarrhoea (IBS-D) is now increasingly recognised, a preliminary, quasi-experimental, before-after and prospective study was conducted on 28 patients to test the effect of a tannin-based supplement on the composition and activity of the microbiota, after 8 weeks of treatment. No statistically significant differences were found in α- or β-diversity. However, sparse Partial Least Squares Discriminant Analysis (sPLS-DA) and Boruta algorithm did reveal significant changes in the relative abundance of specific groups of bacteria, highlighting the involvement of recognized of IBS-D biomarkes, namely Blautia (adj p = 3.5 × 10-11), Eubacterium hallii group (adj p = 5.1 × 10-12) and Dorea (adj p = 1.8 × 10-18), which resulted significantly depleted by the treatment. The modulation of the composition of the gut microbiota had an impact also in the production of short chain fatty acids (SCFAs), which were modulated: acetate and butyrate (n.s. and p = 0.000143) increased while propionate and formate resulted to be significantly reduced (p = 0.00476 and p = 0.00011, respectively), following the supplementation. Finally, the sPLS analysis showed that the strongest association between faecal microbiome composition and clinical symptoms of IBS-D was given by Catenibacterium, which showed a positive correlation with evacuation-related symptoms. Such preliminary findings suggest that tannin supplementation could play an outstanding role in microbiota modulation in IBS-D patients, potentially improving their symptomatology, by selectively acting on the growth and the activity of specific groups of taxa.
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Affiliation(s)
- Silvia Molino
- Silvateam Spa, R&D Unit, San Michele Mondovì, Italy.
| | - Alberto Lerma-Aguilera
- Area de Genòmica i Salut, Fundació per al Foment de la Investigació Sanitária i Biomèdica de la Comunitat Valenciana (FISABIO-Salut Pública), València, Spain
| | - María Marta Piskorz
- Universidad de Buenos Aires, Hospital de Clínicas José de San Martin, Sector Neurogastroenterología del Servicio de Gastroenterología, Buenos Aires, Argentina
| | - Fabiana López Mingorance
- Universidad de Buenos Aires/IBIMOL, Hospital de Clínicas José de San Martin, Programa de Estudios Pancreáticos, Buenos Aires, Argentina
| | - Juan M Montero
- Universidad de Buenos Aires, Hospital de Clínicas José de San Martin, Sector Neurogastroenterología del Servicio de Gastroenterología, Buenos Aires, Argentina
| | - Tatiana Uehara
- Universidad de Buenos Aires, Hospital de Clínicas José de San Martin, Sector Neurogastroenterología del Servicio de Gastroenterología, Buenos Aires, Argentina
| | - Harumi Hashimoto
- Universidad de Buenos Aires, Hospital de Clínicas José de San Martin, Sector Neurogastroenterología del Servicio de Gastroenterología, Buenos Aires, Argentina
| | - Esteban González Ballerga
- Universidad de Buenos Aires, Hospital de Clínicas José de San Martin, Servicio de Gastroenterología, Buenos Aires, Argentina
| | - Jorge A Olmos
- Universidad de Buenos Aires, Hospital de Clínicas José de San Martin, Sector Neurogastroenterología del Servicio de Gastroenterología, Buenos Aires, Argentina
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Yang R, Jiang J, Ouyang J, Zhao Y, Xi B. Efficacy and safety of probiotics in irritable bowel syndrome: A systematic review and meta-analysis. Clin Nutr ESPEN 2024; 60:362-372. [PMID: 38479936 DOI: 10.1016/j.clnesp.2024.02.025] [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: 08/15/2023] [Revised: 02/02/2024] [Accepted: 02/20/2024] [Indexed: 04/13/2024]
Abstract
BACKGROUND Irritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain, distension, and altered bowel habits. Probiotics may alleviate IBS symptoms, but clinical trials remain conflicting. AIMS To conduct a systematic review and meta-analysis of clinical trials to evaluate the efficacy and safety of probiotics for IBS patients. METHODS We searched relevant trials in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar from 2000 to June 2023. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for continuous outcomes. A risk ratio (RR) and a 95% CI were calculated for dichotomous outcomes. RESULTS A total of 20 studies involving 3011 patients were obtained. The results demonstrated that probiotics are more effective than placebo in reducing global IBS symptoms improvement rate (RR = 1.401, 95% CI 1.182-1.662, P < 0.001) and quality of life scores (SMD = 0.286, 95% CI = 0.154-0.418, P < 0.001). Subgroup analyses showed that a shorter treatment time (less than eight weeks) could reduce distension scores (SMD = 0.197, 95% CI = 0.038-0.356, P = 0.015). High doses (daily dose of probiotics ≥ 10ˆ10) or multiple strains of probiotics exhibit beneficial effects on abdominal pain (SMD = 0.412, 95% CI = 0.112-0.711, P = 0.007; SMD = 0.590, 95% CI = 0.050-1.129, P = 0.032; respectively). However, there was no significant benefit on global symptom scores (SMD = 0.387, 95% CI 0.122 to 0.653, P = 0.004) with statistically high inter-study heterogeneity (I2 = 91.9%, P < 0.001). Furthermore, there was no significant inter-group difference in terms of adverse events frequency (RR = 0.997, 95% CI 0.845-1.177, P = 0.973). CONCLUSION Probiotics are effective and safe for IBS patients. High doses or multiple probiotic strains seem preferable, but definite conclusions are challenging due to the high heterogeneity. Large-scale, well-designed, and rigorous trials are needed to confirm their effectiveness.
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Affiliation(s)
- Ruwen Yang
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China
| | - Jiawei Jiang
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China
| | - Jun Ouyang
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China
| | - Yuanpei Zhao
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China
| | - Biao Xi
- Zhenjiang Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Zhenjiang, China.
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5
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Pak R, Cho M, Pride K, Abd-Elsayed A. The Gut Microbiota and Chronic Pain. Curr Pain Headache Rep 2024; 28:259-269. [PMID: 38345694 DOI: 10.1007/s11916-024-01221-x] [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] [Accepted: 01/30/2024] [Indexed: 03/16/2024]
Abstract
PURPOSE OF REVIEW To examine the effects and interactions between gut microbia and chronic pain. RECENT FINDINGS The gut microbiome has been an area of interest in both the scientific and general audience due to a growing body of evidence suggesting its influence in a variety of health and disease states. Communication between the central nervous system (CNS) and gut microbiome is said to be bidirectional, in what is referred to as the gut-brain axis. Chronic pain is a prevalent costly personal and public health burden and so, there is a vested interest in devising safe and efficacious treatments. Numerous studies, many of which are animal studies, have been conducted to examine the gut microbiome's role in the pathophysiology of chronic pain states, such as neuropathy, inflammation, visceral pain, etc. As the understanding of this relationship grows, so does the potential for therapeutic targeting of the gut microbiome in chronic pain.
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Affiliation(s)
- Ray Pak
- Department of Physical Medicine and Rehabilitation, New York Medical College/Metropolitan, New York, NY, USA
| | - Michelle Cho
- Department of Physical Medicine and Rehabilitation, New York Medical College/Metropolitan, New York, NY, USA
| | - Keth Pride
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, B6/319 CSC, Madison, WI, 53792-3272, USA
| | - Alaa Abd-Elsayed
- Department of Anesthesiology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, B6/319 CSC, Madison, WI, 53792-3272, USA.
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6
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Liu X, Zhang B, Zhang Y, Li W, Yin J, Shi A, Wang J, Wang S. 2'-Fucosyllactose Promotes Colonization of Akkermansia muciniphila and Prevents Colitis In Vitro and in Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:4765-4776. [PMID: 38393978 DOI: 10.1021/acs.jafc.3c08305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/25/2024]
Abstract
Akkermansia muciniphila is a potential candidate for ulcerative colitis prevention. Considering that it utilizes 2'-fucosyllactose (2'FL) for growth, 2'FL can be used to enrich the abundance of A. muciniphila in feces. However, whether the crosswalk between 2'FL and A. muciniphila can promote the intestinal colonization of A. muciniphila remains unclear. In this study, we explored the effect and the underlying mechanism of 2'FL on the colonization of A. muciniphila in vitro and in vivo as well as its alleviating effect on colitis. Our results revealed that 2'FL can serve as a carbon source of A. muciniphila to support the growth and increase cell-surface hydrophobicity and the expression of the genes coding fibronectin-binding autotransporter adhesin to promote the adhesion to Caco2/HT29 methotrexate (MTX) cells but not of galactooligosaccharides (GOS) and glucose. Moreover, 2'FL could increase the host mucin formation to promote the adhesion of A. muciniphila to Caco2/HT29 MTX cells but not of GOS and glucose. Furthermore, 2'FL could significantly increase the colonization of A. muciniphila in the gut to alleviate colitis in mice. Overall, the interplay between A. muciniphila and 2'FL is expected to provide an advantageous ecological niche for A. muciniphila so as to confer further health benefits against colitis.
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Affiliation(s)
- Xiaoxia Liu
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Bowei Zhang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Yunhui Zhang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Wanhua Li
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Jia Yin
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Aiying Shi
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Jin Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
| | - Shuo Wang
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
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7
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Reens AL, Cosetta CM, Saur R, Trofimuk O, Brooker SL, Lee ML, Sun AK, McKenzie GJ, Button JE. Tunable control of B. infantis abundance and gut metabolites by co-administration of human milk oligosaccharides. Gut Microbes 2024; 16:2304160. [PMID: 38235736 PMCID: PMC10798361 DOI: 10.1080/19490976.2024.2304160] [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: 09/19/2023] [Accepted: 01/08/2024] [Indexed: 01/19/2024] Open
Abstract
Precision engineering of the gut microbiome holds promise as an effective therapeutic approach for diseases associated with a disruption in this microbial community. Engrafting a live biotherapeutic product (LBP) in a predictable, controllable manner is key to the consistent success of this approach and has remained a challenge for most LBPs under development. We recently demonstrated high-level engraftment of Bifidobacterium longum subsp. infantis (B. infantis) in adults when co-dosed with a specific prebiotic, human milk oligosaccharides (HMO). Here, we present a cellular kinetic-pharmacodynamic approach, analogous to pharmacokinetic-pharmacodynamic-based analyses of small molecule- and biologic-based drugs, to establish how HMO controls expansion, abundance, and metabolic output of B. infantis in a human microbiota-based model in gnotobiotic mice. Our data demonstrate that the HMO dose controls steady-state abundance of B. infantis in the microbiome, and that B. infantis together with HMO impacts gut metabolite levels in a targeted, HMO-dependent manner. We also found that HMO creates a privileged niche for B. infantis expansion across a 5-log range of bacterial inocula. These results demonstrate remarkable control of both B. infantis levels and the microbiome community metabolic outputs using this synbiotic approach, and pave the way for precision engineering of desirable microbes and metabolites to treat a range of diseases.
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Affiliation(s)
| | | | | | | | | | - Martin L. Lee
- Prolacta Bioscience, Duarte, CA, USA
- Department of Biostatistics, University of California Los Angeles Fielding School of Public Health, Los AngelesCA, USA
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8
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Chen M, Yuan L, Xie CR, Wang XY, Feng SJ, Xiao XY, Zheng H. Probiotics for the management of irritable bowel syndrome: a systematic review and three-level meta-analysis. Int J Surg 2023; 109:3631-3647. [PMID: 37565634 PMCID: PMC10651259 DOI: 10.1097/js9.0000000000000658] [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: 06/14/2023] [Accepted: 07/24/2023] [Indexed: 08/12/2023]
Abstract
OBJECTIVE Previous systematic reviews demonstrated a potentially beneficial effect of probiotics on irritable bowel syndrome (IBS). However, these studies are either affected by the inclusion of insufficient trials or by the problem of dependent data across multiple outcomes, and an overall effect size has not been provided. We aimed to determine the effect of probiotics on IBS through a three-level meta-analysis and clarify potential effect moderators. METHODS We searched MEDLINE, Embase, and Web of Science, screening for randomized controlled trials (RCTs) that examine the effect of probiotics on IBS. The primary outcome was the improvement in the severity of global IBS symptoms at the end of treatment. The secondary outcomes were the improvement in abdominal pain and the quality of life. The effect sizes of the probiotics were measured by using the standardized mean difference (SMD) and pooled by a three-level meta-analysis model. RESULTS We included 72 RCTs in the analysis. The meta-analysis showed significantly better overall effect of probiotics than placebo on the global IBS symptoms (SMD -0.55, 95% CI -0.76 to -0.34, P <0.001), abdominal pain (SMD -0.89, 95% CI -1.29 to -0.5, P <0.001) and quality of life (SMD 0.99, 95% CI 0.45 to 1.54, P <0.001), respectively. Moderator analysis found that a treatment duration shorter than 4 weeks was associated with a larger effect size in all the outcomes, and Bacillus probiotics had better improvement on the abdominal pain. CONCLUSIONS Probiotics had a short-term effect and a medium effect size on the global IBS symptoms. Treatment duration and types of probiotics affected the effect size of probiotics, and shorter durations and Bacillus probiotics were associated with better treatment effects. REGISTRATION Open Science Framework.
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Affiliation(s)
- Min Chen
- Department of Colorectal Diseases, Hospital of Chengdu University of Traditional Chinese Medicine
| | - Lu Yuan
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Chao-Rong Xie
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Xiao-Ying Wang
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Si-Jia Feng
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Xin-Yu Xiao
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Hui Zheng
- Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
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9
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Luo Y, Zhang Y, Yang Y, Wu S, Zhao J, Li Y, Kang X, Li Z, Chen J, Shen X, He F, Cheng R. Bifidobacterium infantis and 2'-fucosyllactose supplementation in early life may have potential long-term benefits on gut microbiota, intestinal development, and immune function in mice. J Dairy Sci 2023; 106:7461-7476. [PMID: 37641283 DOI: 10.3168/jds.2023-23367] [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: 02/11/2023] [Accepted: 05/10/2023] [Indexed: 08/31/2023]
Abstract
The health benefits of nutritional interventions targeting the gut microbiota in early life are transient, such as probiotics, prebiotics, and synbiotics. This study sought to determine whether supplementation with Bifidobacterium infantis 79 (B79), 2'-fucosyllactose (2'-FL), or both (B79+2'FL) would lead to persistent health benefits in neonatal BALB/c mice. We found that at postnatal day (PND) 21, Ki67 and MUC2 expression increased, while total serum IgE content decreased in the B79, 2'-FL, and B79+2'-FL groups. The gut microbiota structure and composition altered as well. The levels of propionic acid, sIgA, and IL-10 increased in the 2'-FL group. Moreover, butyric acid content increased, while IL-6, IL-12p40, and tumor necrosis factor-α decreased in the B79+2'-FL group. At PND 56, Ki67 and MUC2 expression increased, whereas the gut microbiota remained altered in all 3 groups. The serum total IgG level increased only in the B79+2'-FL group. In conclusion, our study suggests that early-life supplementation with B79, 2'-FL, or their combination persistently alters the gut microbiome and promotes intestinal development; the immunomodulatory capacity of B79 and 2'-FL occurs during weaning, and their combination may persist into adulthood.
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Affiliation(s)
- Yating Luo
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Yujie Zhang
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Yang Yang
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Simou Wu
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Jincheng Zhao
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Yun Li
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Xiaohong Kang
- R&D Center, Inner Mongolia Meng Niu Dairy Industry (Group) Co. Ltd., 011500 Hohhot, Inner Mongolia, China
| | - Zhouyong Li
- R&D Center, Inner Mongolia Meng Niu Dairy Industry (Group) Co. Ltd., 011500 Hohhot, Inner Mongolia, China
| | - Jianguo Chen
- R&D Center, Inner Mongolia Meng Niu Dairy Industry (Group) Co. Ltd., 011500 Hohhot, Inner Mongolia, China; Beijing YuGen Pharmaceutical Co. Ltd., 102600 Beijing, China
| | - Xi Shen
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China
| | - Fang He
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.
| | - Ruyue Cheng
- Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, 610041 Chengdu, Sichuan, China.
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10
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Amieva-Balmori M, García-Mazcorro JF, Martínez-Conejo A, Hernández-Ramírez GA, García-Zermeño KR, Rodríguez-Aguilera O, Aja-Cadena M, Barradas-Cortés M, Quigley EMM, Remes-Troche JM. Fecal bacterial microbiota in constipated patients before and after eight weeks of daily Bifidobacterium infantis 35624 administration. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2023; 88:369-380. [PMID: 35810091 DOI: 10.1016/j.rgmxen.2022.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/04/2022] [Indexed: 10/17/2022]
Abstract
INTRODUCTION AND AIM In recent years, probiotics have been used in functional gastrointestinal disorders, including chronic constipation (CC). The effect of Bifidobacterium infantis strain 35624 on the gut microbiota of CC patients has not been previously studied. Our aim was to analyze the fecal microbiota of constipated patients, before and after consuming a single-strain probiotic (B. infantis strain 35624). MATERIALS AND METHODS We used 16S rRNA gene high-throughput sequencing to analyze the fecal microbiota of female patients (n=13) with CC. Patients were instructed to ingest one capsule of Alflorex® (containing 1×109 CFUs/g B. infantis strain 35624) daily for eight weeks. Fecal samples were obtained at the baseline and end (final) of probiotic administration. RESULTS Alpha diversity metrics did not differ between the baseline and final periods. The butyrate producer, Oscillospira, was the taxon most strongly correlated with amplicon sequence variants (R2=0.55, p<0.0001). Except for a few bacterial taxa, there were no significant differences in relative abundance between the baseline and final periods. Beta-diversity measures also showed limited evidence for the differences between the two time periods. CONCLUSIONS The results suggest that the fecal bacterial microbiota remains stable in constipated women consuming a single-strain probiotic. Those findings may be helpful in better understanding probiotic functioning in patients with digestive disorders.
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Affiliation(s)
- M Amieva-Balmori
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - J F García-Mazcorro
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - A Martínez-Conejo
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - G A Hernández-Ramírez
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - K R García-Zermeño
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - O Rodríguez-Aguilera
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - M Aja-Cadena
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - M Barradas-Cortés
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México
| | - E M M Quigley
- Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, TX, USA
| | - J M Remes-Troche
- Laboratorio de Fisiología Digestiva y Motilidad Gastrointestinal, Instituto de Investigaciones Medico-Biológicas, Universidad Veracruzana, Veracruz, México.
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11
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Button JE, Cosetta CM, Reens AL, Brooker SL, Rowan-Nash AD, Lavin RC, Saur R, Zheng S, Autran CA, Lee ML, Sun AK, Alousi AM, Peterson CB, Koh AY, Rechtman DJ, Jenq RR, McKenzie GJ. Precision modulation of dysbiotic adult microbiomes with a human-milk-derived synbiotic reshapes gut microbial composition and metabolites. Cell Host Microbe 2023; 31:1523-1538.e10. [PMID: 37657443 DOI: 10.1016/j.chom.2023.08.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 06/13/2023] [Accepted: 08/07/2023] [Indexed: 09/03/2023]
Abstract
Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol sulfate, metabolites that impact host inflammatory status. Furthermore, Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts lactate produced by B. infantis to propionate, an important mediator of host physiology. These results suggest that the synbiotic reproducibly and predictably modulates recovery of a dysbiotic microbiome.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Martin L Lee
- Prolacta Bioscience, Duarte, CA 91010, USA; Department of Biostatistics, University of California Los Angeles, Fielding School of Public Health, Los Angeles, CA 90095, USA
| | - Adam K Sun
- Prolacta Bioscience, Duarte, CA 91010, USA
| | - Amin M Alousi
- Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Christine B Peterson
- Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | - Andrew Y Koh
- Department of Pediatrics, Division of Hematology/Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | | | - Robert R Jenq
- Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
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12
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Xie P, Luo M, Deng X, Fan J, Xiong L. Outcome-Specific Efficacy of Different Probiotic Strains and Mixtures in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis. Nutrients 2023; 15:3856. [PMID: 37686889 PMCID: PMC10490209 DOI: 10.3390/nu15173856] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 08/30/2023] [Accepted: 09/01/2023] [Indexed: 09/10/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common gastrointestinal disease. The efficacy of different probiotics in treating IBS remains controversial. This network meta-analysis aimed to compare and rank the outcome-specific efficacy of different probiotic strains or combinations in adults with IBS. We searched the literature up to June 2023. Randomized controlled trials (RCTs) that evaluated the efficacy of probiotics in IBS were included. A frequentist framework was used to perform this study. In total, 9253 participants from 81 RCTs were included in the study. Four probiotic strains and five mixtures were significantly superior to placebo in improving IBS Symptom Severity Scale, among which Lactobacillus acidophilus DDS-1 ranked first (surface under the cumulative ranking, SUCRA, 92.9%). A mixture containing five probiotics (SUCRA, 100%) ranked first in improving the IBS-Quality of life. Bacillus coagulans MTCC 5856 (SUCRA, 96.9%) and Bacillus coagulans Unique IS2 (SUCRA, 92.6%) were among the most effective probiotics for improving abdominal pain. Three probiotic strains and two mixtures were effective in alleviating abdominal bloating. Four probiotic strains and a mixture were significantly superior to placebo in reducing the bowel movement frequency in diarrhea-predominant IBS (IBS-D). Bacillus coagulans MTCC 5856 (SUCRA, 99.6%) and Saccharomyces cerevisiae CNCM I-3856 (SUCRA, 89.7%) were among the most effective probiotics for improving the Bristol stool form scale of IBS-D. Only some probiotics are effective for particular outcomes in IBS patients. This study provided the first ranking of outcome-specific efficacy of different probiotic strains and combinations in IBS. Further studies are needed to confirm these results.
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Affiliation(s)
| | | | | | | | - Lishou Xiong
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
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13
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Radford-Smith DE, Anthony DC. Prebiotic and Probiotic Modulation of the Microbiota-Gut-Brain Axis in Depression. Nutrients 2023; 15:nu15081880. [PMID: 37111100 PMCID: PMC10146605 DOI: 10.3390/nu15081880] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Revised: 04/07/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Emerging evidence demonstrates that alterations to the gut microbiota can affect mood, suggesting that the microbiota-gut-brain (MGB) axis contributes to the pathogenesis of depression. Many of these pathways overlap with the way in which the gut microbiota are thought to contribute to metabolic disease progression and obesity. In rodents, prebiotics and probiotics have been shown to modulate the composition and function of the gut microbiota. Together with germ-free rodent models, probiotics have provided compelling evidence for a causal relationship between microbes, microbial metabolites, and altered neurochemical signalling and inflammatory pathways in the brain. In humans, probiotic supplementation has demonstrated modest antidepressant effects in individuals with depressive symptoms, though more studies in clinically relevant populations are needed. This review critically discusses the role of the MGB axis in depression pathophysiology, integrating preclinical and clinical evidence, as well as the putative routes of communication between the microbiota-gut interface and the brain. A critical overview of the current approaches to investigating microbiome changes in depression is provided. To effectively translate preclinical breakthroughs in MGB axis research into novel therapies, rigorous placebo-controlled trials alongside a mechanistic and biochemical understanding of prebiotic and probiotic action are required from future research.
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Affiliation(s)
- Daniel E Radford-Smith
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
- Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
- Department of Psychiatry, University of Oxford, Warneford Hospital, Warneford Lane, Oxford OX3 7JX, UK
| | - Daniel C Anthony
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
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14
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Cichońska P, Kowalska E, Ziarno M. The Survival of Psychobiotics in Fermented Food and the Gastrointestinal Tract: A Review. Microorganisms 2023; 11:microorganisms11040996. [PMID: 37110420 PMCID: PMC10142889 DOI: 10.3390/microorganisms11040996] [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: 03/25/2023] [Revised: 04/04/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
In recent years, scientists have been particularly interested in the gut-brain axis, as well as the impact of probiotics on the nervous system. This has led to the creation of the concept of psychobiotics. The present review describes the mechanisms of action of psychobiotics, their use in food products, and their viability and survival during gastrointestinal passage. Fermented foods have a high potential of delivering probiotic strains, including psychobiotic ones. However, it is important that the micro-organisms remain viable in concentrations ranging from about 106 to 109 CFU/mL during processing, storage, and digestion. Reports indicate that a wide variety of dairy and plant-based products can be effective carriers for psychobiotics. Nonetheless, bacterial viability is closely related to the type of food matrix and the micro-organism strain. Studies conducted in laboratory conditions have shown promising results in terms of the therapeutic properties and viability of probiotics. Because human research in this field is still limited, it is necessary to broaden our understanding of the survival of probiotic strains in the human digestive tract, their resistance to gastric and pancreatic enzymes, and their ability to colonize the microbiota.
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Affiliation(s)
- Patrycja Cichońska
- Department of Food Technology and Assessment, Institute of Food Science, Warsaw University of Life Sciences-SGGW (WULS-SGGW), Nowoursynowska 159c St., 02-776 Warsaw, Poland
| | - Ewa Kowalska
- Department of Food Technology and Assessment, Institute of Food Science, Warsaw University of Life Sciences-SGGW (WULS-SGGW), Nowoursynowska 159c St., 02-776 Warsaw, Poland
| | - Małgorzata Ziarno
- Department of Food Technology and Assessment, Institute of Food Science, Warsaw University of Life Sciences-SGGW (WULS-SGGW), Nowoursynowska 159c St., 02-776 Warsaw, Poland
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15
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Schmidt T, Meller S, Meyerhoff N, Twele F, Zanghi B, Volk HA. A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial design to investigate the potential of psychobiotics on seizure semiology and comorbidities in canine epilepsy: study protocol. BMC Vet Res 2023; 19:57. [PMID: 36864510 PMCID: PMC9983181 DOI: 10.1186/s12917-023-03609-0] [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: 09/21/2022] [Accepted: 02/16/2023] [Indexed: 03/04/2023] Open
Abstract
BACKGROUND Epilepsy is the most common chronic neurological disease in dogs. More than two-thirds of these patients suffer from associated behavioural comorbidities. The latter could have their origin in partially overlapping pathomechanisms, with the intestinal microbiome as a potential key link between them. The current arsenal of drugs for epilepsy management remains limited. Most canine patients continue to have seizures despite treatment and the occurrence of comorbidities is not sufficiently addressed, limiting quality of life of affected dogs and owners. Therefore, novel additional epilepsy management options are urgently needed. The microbiome-gut-brain axis may serve as a new target for the development of innovative multimodal therapeutic approaches to overcome current shortcomings in epilepsy management. METHODS A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial was designed to investigate the potential of the psychobiotic Bifidobacterium longum on behavioural comorbidities in canine epilepsy. Seizure semiology will be evaluated as a secondary outcome measure. Thirty-four privately owned dogs are planned to be included in the ongoing study meeting the following inclusion criteria: Dogs displaying increased anxiety/fear behaviour since the start of the idiopathic epilepsy. Tier II confidence level of the International Veterinary Epilepsy Task Force for the diagnosis of idiopathic epilepsy, with a maximum seizure interval of 3 month and a minimum of three generalised seizures within that period and chronically treated with at least one antiseizure drug without improvement in seizure frequency Each dog will receive the allocated supplement (probiotic vs. placebo) alongside its normal diet for a 3-month period. After a three-week wash out period, the second phase starts by administering the respective other supplement for another 3 months. DISCUSSION The current study considers modern high-quality standards for epilepsy medication trials. Common biasing effects should be limited to a possible minimum (regression-to-the mean effect, placebo effect, observer effect), ensuring a high validity and accuracy of the acquired results, thus enabling a representative nature of the efficacy of Bifidobacterium longum as add-on supplement for dogs suffering from epilepsy and its comorbidities. This publication should provide a description of the study procedure and data acquisition methods, including prognosed statistical analysis.
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Affiliation(s)
- Teresa Schmidt
- grid.412970.90000 0001 0126 6191Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Sebastian Meller
- grid.412970.90000 0001 0126 6191Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Nina Meyerhoff
- grid.412970.90000 0001 0126 6191Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Friederike Twele
- grid.412970.90000 0001 0126 6191Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Brian Zanghi
- Research and Development, Nestlé Purina PetCare, St. Louis, MO USA
| | - Holger Andreas Volk
- Department of Small Animal Medicine and Surgery, University of Veterinary Medicine Hannover, Hannover, Germany. .,Centre for Systems Neuroscience, University of Veterinary Medicine Hannover, Hannover, Germany.
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16
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Ramirez ZE, Surana NK. Ruminococcus gnavus and Limosilactobacillus reuteri Regulate Reg3γ Expression through Multiple Pathways. Immunohorizons 2023; 7:228-234. [PMID: 36943156 PMCID: PMC10563382 DOI: 10.4049/immunohorizons.2200096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 02/21/2023] [Indexed: 03/23/2023] Open
Abstract
Epithelium-derived antimicrobial peptides represent an evolutionarily ancient defense mechanism against pathogens. Regenerating islet-derived protein 3 γ (Reg3γ), the archetypal intestinal antimicrobial peptide, is critical for maintaining host-microbe interactions. Expression of Reg3γ is known to be regulated by the microbiota through two different pathways, although it remains unknown whether specific Reg3γ-inducing bacteria act via one or both of these pathways. In recent work, we identified Ruminococcus gnavus and Limosilactobacillus reuteri as commensal bacteria able to induce Reg3g expression. In this study, we show these bacteria require myeloid differentiation primary response protein 88 and group 3 innate lymphoid cells for induction of Reg3γ in mice. Interestingly, we find that R. gnavus and L. reuteri suppress Reg3γ in the absence of either myeloid differentiation primary response protein 88 or group 3 innate lymphoid cells. In addition, we demonstrate that colonization by these bacteria is not required for induction of Reg3γ, which occurs several days after transient exposure to the organisms. Taken together, our findings highlight the complex mechanisms underlying microbial regulation of Reg3γ.
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Affiliation(s)
- Zeni E. Ramirez
- Division of Infectious Diseases, Department of Pediatrics, Duke University School of Medicine, Durham, NC
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC
| | - Neeraj K. Surana
- Division of Infectious Diseases, Department of Pediatrics, Duke University School of Medicine, Durham, NC
- Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC
- Department of Immunology, Duke University School of Medicine, Durham, NC
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17
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Vedantam S, Graff E, Khakoo NS, Khakoo NS, Pearlman M. Food as Medicine: How to Influence the Microbiome and Improve Symptoms in Patients with Irritable Bowel Syndrome. Curr Gastroenterol Rep 2023; 25:52-60. [PMID: 36763098 DOI: 10.1007/s11894-023-00861-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2022] [Indexed: 02/11/2023]
Abstract
PURPOSE OF REVIEW This review highlights effects of dietary interventions on the gut microbiome and gastrointestinal symptoms in those with irritable bowel syndrome (IBS). RECENT FINDINGS It is hypothesized that gut dysbiosis factors into the pathophysiology of IBS. Various diets that influence the microbiome and intestinal physiology may have therapeutic properties. At present, data suggests that implementation of personalized dietary interventions have a mixed, but overall positive effect on the gut microbiome and IBS symptoms. The effect of dietary modification on the gut microbiome and GI symptoms in patients with IBS is a topic that has garnered interest due to the increasing prevalence of IBS and heightened awareness of the importance of gut health. The composition of the gut microbiome may be modulated by promoting fiber intake and implementation of exclusionary diets and dietary supplements; however, additional studies are needed to provide evidence-based guidelines in this patient population.
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Affiliation(s)
- Shyam Vedantam
- Department of Medicine, University of Miami, Miami, FL, USA
| | - Erica Graff
- Department of Medicine, University of Miami, Miami, FL, USA
| | | | | | - Michelle Pearlman
- Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami, Miami, FL, USA. .,Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, 1120 NW 14th Street, Miami, FL, 33136, USA.
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18
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Nakamura Y, Suzuki S, Murakami S, Nishimoto Y, Higashi K, Watarai N, Umetsu J, Ishii C, Ito Y, Mori Y, Kohno M, Yamada T, Fukuda S. Integrated gut microbiome and metabolome analyses identified fecal biomarkers for bowel movement regulation by Bifidobacterium longum BB536 supplementation: A RCT. Comput Struct Biotechnol J 2022; 20:5847-5858. [PMID: 36382178 PMCID: PMC9636538 DOI: 10.1016/j.csbj.2022.10.026] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 10/19/2022] [Accepted: 10/19/2022] [Indexed: 11/03/2022] Open
Abstract
Background Bifidobacterium longum BB536 supplementation can be used to regulate bowel movements in various people, including healthy subjects and patients with irritable bowel syndrome (IBS); however, individuals vary in their responses to B. longum BB536 treatment. One putative factor is the gut microbiota; recent studies have reported that the gut microbiota mediates the effects of diet or drugs on the host. Here, we investigated intestinal features, such as the microbiome and metabolome, related to B. longum BB536 effectiveness in increasing bowel movement frequency. Results A randomized, double-blind controlled crossover trial was conducted with 24 adults who mainly tended to be constipated. The subjects received a two-week dietary intervention consisting of B. longum BB536 in acid-resistant seamless capsules or similarly encapsulated starch powder as the placebo control. Bowel movement frequency was recorded daily, and fecal samples were collected at several time points, and analyzed by metabologenomic approach that consists of an integrated analysis of metabolome data obtained using mass spectrometry and microbiome data obtained using high-throughput sequencing. There were differences among subjects in B. longum intake-induced bowel movement frequency. The responders were predicted by machine learning based on the microbiome and metabolome features of the fecal samples collected before B. longum intake. The abundances of eight bacterial genera were significantly different between responders and nonresponders. Conclusions Intestinal microbiome and metabolome profiles might be utilized as potential markers of improved bowel movement after B. longum BB536 supplementation. These findings have implications for the development of personalized probiotic treatments.
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Key Words
- 16S rRNA gene sequence
- AUROC, area under the receiver operating characteristic curve
- Bifidobacteria
- CE-TOFMS, capillary electrophoresis time-of-flight mass spectrometry
- CSA, D-camphor-10-sulfonic acid
- ESVs, exact sequence variants
- FDR, false discovery rate
- Gut microbiota
- IBD, inflammatory bowel disease
- IBS, irritable bowel syndrome
- ITT, intention-to-treat
- MCMC, Markov Chain Monte Carlo
- MDS, multidimensional scaling
- Machine learning
- Metabologenomics
- NRs, nonresponders
- PP, per-protocol population
- PSRF, potential scale reduction factor
- Probiotics
- SCFAs, short-chain fatty acids
- SRs, strong responders
- WAIC, Widely Applicable Information Criterion
- WRs, weak responders
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Affiliation(s)
- Yuya Nakamura
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Shinya Suzuki
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
- Education Academy of Computational Life Science (ACLS), 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Shinnosuke Murakami
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Institute for Advanced Biosciences, Keio University, 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
| | | | - Koichi Higashi
- National Institute of Genetics, Genome Evolution Laboratory, Yata 1111, Mishima 411-8540, Japan
| | - Naoki Watarai
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Junpei Umetsu
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Chiharu Ishii
- Institute for Advanced Biosciences, Keio University, 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
| | - Yutaro Ito
- Institute for Advanced Biosciences, Keio University, 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
| | - Yuka Mori
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
| | - Mamiko Kohno
- MORISHITA JINTAN CO., LTD, Health Care Product Department, Research & Development Division, 1-2-40 Tamatsukuri, Chuo-ku, Osaka 540-8566, Japan
| | - Takuji Yamada
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Department of Life Science and Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan
| | - Shinji Fukuda
- Metagen Inc., 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Institute for Advanced Biosciences, Keio University, 246-2 Kakuganji, Tsuruoka, Yamagata 997-0052, Japan
- Transborder Medical Research Center, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan
- Gut Environmental Design Group, Kanagawa Institute of Industrial Science and Technology, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan
- Laboratory for Regenerative Microbiology, Juntendo University Graduate School of Medicine, Hongo, Tokyo 113-8421, Japan
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19
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Iribarren C, Maasfeh L, Öhman L, Simrén M. Modulating the gut microenvironment as a treatment strategy for irritable bowel syndrome: a narrative review. GUT MICROBIOME (CAMBRIDGE, ENGLAND) 2022; 3:e7. [PMID: 39295774 PMCID: PMC11406401 DOI: 10.1017/gmb.2022.6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 06/02/2022] [Accepted: 07/26/2022] [Indexed: 09/21/2024]
Abstract
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction with a complex pathophysiology. Growing evidence suggests that alterations of the gut microenvironment, including microbiota composition and function, may be involved in symptom generation. Therefore, attempts to modulate the gut microenvironment have provided promising results as an indirect approach for IBS management. Antibiotics, probiotics, prebiotics, food and faecal microbiota transplantation are the main strategies for alleviating IBS symptom severity by modulating gut microbiota composition and function (eg. metabolism), gut barrier integrity and immune activity, although with varying efficacy. In this narrative review, we aim to provide an overview of the current approaches targeting the gut microenvironment in order to indirectly manage IBS symptoms.
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Affiliation(s)
- Cristina Iribarren
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lujain Maasfeh
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Lena Öhman
- Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Magnus Simrén
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, NC, USA
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20
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Effectiveness and Safety of Probiotics for Patients with Constipation-Predominant Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials. Nutrients 2022; 14:nu14122482. [PMID: 35745212 PMCID: PMC9231226 DOI: 10.3390/nu14122482] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 06/05/2022] [Accepted: 06/12/2022] [Indexed: 12/13/2022] Open
Abstract
To perform a systematic review and meta-analysis to evaluate the effectiveness and safety of probiotics in the treatment of constipation-predominant irritable bowel syndrome (IBS-C), we searched for randomized controlled trials (RCTs) comparing probiotic care versus placebos for patients with IBS-C in five comprehensive databases (March 2022). The risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool. RevMan 5.3 was used to perform a meta-analysis on stool consistency, abdominal pain, bloating, quality of life (QoL), fecal Bifidobacterium and Lactobacillus counts, and adverse events. The GRADE approach was used to evaluate the certainty of the evidence. Ten RCTs involving 757 patients were included. Only three studies were rated as having a low risk of bias. The meta-analysis results show that, compared to the placebo, probiotics significantly improved stool consistency (MD = 0.72, 95% CI (0.18, 1.26), p < 0.05, low quality) and increased the number of fecal Bifidobacteria (MD = 1.75, 95% CI (1.51, 2.00), p < 0.05, low quality) and Lactobacillus (MD = 1.69, 95% CI (1.48, 1.89), p < 0.05, low quality), while no significant differences were found in abdominal pain scores, bloating scores, QoL scores, or the incidence of adverse events (p > 0.05). The low-to-very low certainty evidence suggests that probiotics might improve the stool consistency of patients with IBS-C and increase the number of Bifidobacteria and Lactobacilli in feces with good safety. However, more high-quality studies with large samples are needed to verify the findings.
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21
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Button JE, Autran CA, Reens AL, Cosetta CM, Smriga S, Ericson M, Pierce JV, Cook DN, Lee ML, Sun AK, Alousi AM, Koh AY, Rechtman DJ, Jenq RR, McKenzie GJ. Dosing a synbiotic of human milk oligosaccharides and B. infantis leads to reversible engraftment in healthy adult microbiomes without antibiotics. Cell Host Microbe 2022; 30:712-725.e7. [PMID: 35504279 DOI: 10.1016/j.chom.2022.04.001] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 03/11/2022] [Accepted: 04/07/2022] [Indexed: 11/30/2022]
Abstract
Predictable and sustainable engraftment of live biotherapeutic products into the human gut microbiome is being explored as a promising way to modulate the human gut microbiome. We utilize a synbiotic approach pairing the infant gut microbe Bifidobacterium longum subspecies infantis (B. infantis) and human milk oligosaccharides (HMO). B. infantis, which is typically absent in adults, engrafts into healthy adult microbiomes in an HMO-dependent manner at a relative abundance of up to 25% of the bacterial population without antibiotic pretreatment or adverse effects. Corresponding changes in metabolites are detected. Germ-free mice transplanted with dysbiotic human microbiomes also successfully engraft with B. infantis in an HMO-dependent manner, and the synbiotic augments butyrate levels both in this in vivo model and in in vitro cocultures of the synbiotic with specific Firmicutes species. Finally, the synbiotic inhibits the growth of enteropathogens in vitro. Our findings point to a potential safe mechanism for ameliorating dysbioses characteristic of numerous human diseases.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | - Adam K Sun
- Prolacta Bioscience, Duarte, CA 91010, USA
| | - Amin M Alousi
- Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Andrew Y Koh
- Department of Pediatrics, Division of Hematology/Oncology, The University of Texas Southwestern Medical Center, Dallas, TX 75235, USA; Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Microbiology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
| | | | - Robert R Jenq
- Department of Genomic Medicine, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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22
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Xie CR, Tang B, Shi YZ, Peng WY, Ye K, Tao QF, Yu SG, Zheng H, Chen M. Low FODMAP Diet and Probiotics in Irritable Bowel Syndrome: A Systematic Review With Network Meta-analysis. Front Pharmacol 2022; 13:853011. [PMID: 35355730 PMCID: PMC8959572 DOI: 10.3389/fphar.2022.853011] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 02/16/2022] [Indexed: 12/12/2022] Open
Abstract
Background: Probiotic and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet are two commonly used management approaches for patients with irritable bowel syndrome (IBS). We aimed to evaluate the most effective combinations and components among different probiotics or low FODMAP diet through component network meta-analysis (NMA). Methods: We searched Embase, Ovid Medline, and Web of Science from inception to 21 January 2021. Randomized controlled trials (RCTs) examining the efficacy of probiotics and low FODMAP diet for IBS were included, with placebo, sham diet, or conventional treatments as controls. Binary outcomes were compared among treatments using the relative ratio (RR). A minimally contextualized framework recommended by the GRADE group was used to evaluate the certainty of evidence. The primary efficacy outcome was the relief of global IBS symptoms, and the secondary efficacy outcome was the reduction in IBS symptom scores or abdominal pain scores. Key Results: We included 76 RCTs (n = 8058) after screening 1940 articles. Eight RCTs were classified as low risk of bias. Standard network meta-analysis (NMA) showed that Lactobacillus (RR 1.74, 95% CI 1.22–2.48) and Bifidobacterium (RR 1.76, 95% CI 1.01–3.07) were the most effective for the primary efficacy outcome (high certainty evidence); component NMA showed that Bacillus (RR 5.67, 95% CI 1.88 to 17.08, p = 0.002) and Lactobacillus (RR 1.42, 95% CI 1.07 to 1.91, p = 0.017) were among the most effective components. The results of standard NMA and CNMA analysis of the improvement of overall IBS symptom scores or abdominal pain scores were consistent with this finding. Conclusion:Lactobacillus was the most effective component for the relief of IBS symptoms; Bifidobacterium and Bacillus were possibly effective and need further verification. Systematic Review Registration: website, identifier registration number.
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Affiliation(s)
- Chao-Rong Xie
- The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Bin Tang
- Digestive Department, People's Hospital of Zhongjiang County, Zhongjiang, China
| | - Yun-Zhou Shi
- The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Wen-Yan Peng
- The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Kun Ye
- The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qing-Feng Tao
- The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shu-Guang Yu
- The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Hui Zheng
- The Third Hospital/Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Min Chen
- Department of Colorectal Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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23
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Quigley E. Clinical trials of probiotics in patients with IBS - some points to consider. J Neurogastroenterol Motil 2022; 28:204-211. [PMID: 35189598 PMCID: PMC8978119 DOI: 10.5056/jnm22012] [Citation(s) in RCA: 11] [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: 01/29/2022] [Accepted: 02/09/2022] [Indexed: 11/20/2022] Open
Abstract
Probiotic products in various formulations are widely used world-wide for a seemingly limitless range of indications--from health maintenance to the alleviation of common intestinal ailments and on to the prevention and treatment of a variety of gastrointestinal diseases and disorders. The profusion of probiotic preparations, together with a very different regulatory climate compared to that which surrounds drugs and devices, leaves the consumer and the health care professional alike bewildered. How can they tell which products truly are what they claim to be? Which probiotics should be chosen for a particular clinical situation? These questions are thrown into stark relief when one evaluates the literature on probiotics in irritable bowel syndrome. To provide some guidance the current probiotic landscape is reviewed and some achievable steps to help bring light to a murky environment are proposed. The goal is to promote verifiable quality control and generate actionable evidence from well-conducted clinical trials of probiotic products in irritable bowel syndrome.
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Affiliation(s)
- Eamonn Quigley
- Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College Houston, Texas, USA
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24
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Sabaté JM, Iglicki F. Effect of Bifidobacterium longum 35624 on disease severity and quality of life in patients with irritable bowel syndrome. World J Gastroenterol 2022; 28:732-744. [PMID: 35317278 PMCID: PMC8891724 DOI: 10.3748/wjg.v28.i7.732] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 11/18/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bifidobacterium longum 35624 has shown efficacy in improving irritable bowel syndrome (IBS) symptoms compared with placebo in double-blind randomized studies. However, few data are available from real-life clinical practice or from studies that used Rome IV criteria to diagnose IBS.
AIM To assess the effect of B. longum 35624 on IBS severity and quality of life in a real-life setting.
METHODS From November 2018 to January 2020, 278 patients with IBS (according to Rome IV criteria) were enrolled in a prospective, open-label, multicenter observational study by private practice gastroenterologists to received one capsule of B. longum 35624 (109 colony-forming units) per day for 30 d. Participation in the study was independently proposed to patients during spontaneous consultations. Disease severity (assessed by the IBS severity scoring system) and patient quality of life (assessed by the IBS quality of life questionnaire) were compared between the inclusion visit (baseline) and the visit at the end of 30 d of treatment. The characteristics of patients were described at baseline. Continuous variables comparisons between inclusion and end-of-treatment visits were performed using the t-test and Kruskal-Wallis test. Categorical variables comparisons were performed using the χ2 test.
RESULTS A total of 233 patients, with a mean age of 51.4 years and composed of 71.2% women, were included in the study. Of these patients, 48.1% had moderate IBS and 46.4% had severe IBS. After a 30-d treatment period with one B. longum 35624 capsule per day, a significant decrease in IBS severity was observed compared to baseline (mean ± SD, IBS severity scoring system scores: 208 ± 104 vs 303 ± 81, P < 0.001) and 57% of patients moved to lower severity categories or achieved remission. The quality of life of patients was also improved by the treatment (IBS Quality of Life questionnaire score: 68.8 ± 20.9 vs 60.2 ± 20.5; P < 0.001) and 63.8% of patients were satisfied with the treatment.
CONCLUSION Thirty days of treatment with B. longum 35624 reduces disease severity and improves the quality of life of patients with IBS, particularly those with the most severe forms of IBS.
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Affiliation(s)
- Jean-Marc Sabaté
- Department of Gastroenterology, Hôpital Avicenne, AP-HP, Sorbonne Paris Nord, Bobigny 93000, France
- INSERM U-987, Pathophysiology and Clinical Pharmacology of Pain, Ambroise Paré Hospital, Boulogne-Billancourt 92100, France
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25
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Singh R, Zogg H, Ghoshal UC, Ro S. Current Treatment Options and Therapeutic Insights for Gastrointestinal Dysmotility and Functional Gastrointestinal Disorders. Front Pharmacol 2022; 13:808195. [PMID: 35145413 PMCID: PMC8822166 DOI: 10.3389/fphar.2022.808195] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 01/04/2022] [Indexed: 12/12/2022] Open
Abstract
Functional gastrointestinal disorders (FGIDs) have been re-named as disorders of gut-brain interactions. These conditions are not only common in clinical practice, but also in the community. In reference to the Rome IV criteria, the most common FGIDs, include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Additionally, there is substantial overlap of these disorders and other specific gastrointestinal motility disorders, such as gastroparesis. These disorders are heterogeneous and are intertwined with several proposed pathophysiological mechanisms, such as altered gut motility, intestinal barrier dysfunction, gut immune dysfunction, visceral hypersensitivity, altered GI secretion, presence and degree of bile acid malabsorption, microbial dysbiosis, and alterations to the gut-brain axis. The treatment options currently available include lifestyle modifications, dietary and gut microbiota manipulation interventions including fecal microbiota transplantation, prokinetics, antispasmodics, laxatives, and centrally and peripherally acting neuromodulators. However, treatment that targets the pathophysiological mechanisms underlying the symptoms are scanty. Pharmacological agents that are developed based on the cellular and molecular mechanisms underlying pathologies of these disorders might provide the best avenue for future pharmaceutical development. The currently available therapies lack long-term effectiveness and safety for their use to treat motility disorders and FGIDs. Furthermore, the fundamental challenges in treating these disorders should be defined; for instance, 1. Cause and effect cannot be disentangled between symptoms and pathophysiological mechanisms due to current therapies that entail the off-label use of medications to treat symptoms. 2. Despite the knowledge that the microbiota in our gut plays an essential part in maintaining gut health, their exact functions in gut homeostasis are still unclear. What constitutes a healthy microbiome and further, the precise definition of gut microbial dysbiosis is lacking. More comprehensive, large-scale, and longitudinal studies utilizing multi-omics data are needed to dissect the exact contribution of gut microbial alterations in disease pathogenesis. Accordingly, we review the current treatment options, clinical insight on pathophysiology, therapeutic modalities, current challenges, and therapeutic clues for the clinical care and management of functional dyspepsia, gastroparesis, irritable bowel syndrome, functional constipation, and functional diarrhea.
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Affiliation(s)
- Rajan Singh
- Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, United States
| | - Hannah Zogg
- Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, United States
| | - Uday C Ghoshal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Seungil Ro
- Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, Reno, NV, United States
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26
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Zimmermann C, Wagner AE. Impact of Food-Derived Bioactive Compounds on Intestinal Immunity. Biomolecules 2021; 11:biom11121901. [PMID: 34944544 PMCID: PMC8699755 DOI: 10.3390/biom11121901] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2021] [Revised: 12/14/2021] [Accepted: 12/16/2021] [Indexed: 12/12/2022] Open
Abstract
The gastrointestinal system is responsible for the digestion and the absorption of nutrients. At the same time, it is essentially involved in the maintenance of immune homeostasis. The strongest antigen contact in an organism takes place in the digestive system showing the importance of a host to develop mechanisms allowing to discriminate between harmful and harmless antigens. An efficient intestinal barrier and the presence of a large and complex part of the immune system in the gut support the host to implement this task. The continuous ingestion of harmless antigens via the diet requires an efficient immune response to reliably identify them as safe. However, in some cases the immune system accidentally identifies harmless antigens as dangerous leading to various diseases such as celiac disease, inflammatory bowel diseases and allergies. It has been shown that the intestinal immune function can be affected by bioactive compounds derived from the diet. The present review provides an overview on the mucosal immune reactions in the gut and how bioactive food ingredients including secondary plant metabolites and probiotics mediate its health promoting effects with regard to the intestinal immune homeostasis.
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27
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Layer P, Andresen V, Allescher H, Bischoff SC, Claßen M, Elsenbruch S, Freitag M, Frieling T, Gebhard M, Goebel-Stengel M, Häuser W, Holtmann G, Keller J, Kreis ME, Kruis W, Langhorst J, Jansen PL, Madisch A, Mönnikes H, Müller-Lissner S, Niesler B, Pehl C, Pohl D, Raithel M, Röhrig-Herzog G, Schemann M, Schmiedel S, Schwille-Kiuntke J, Storr M, Preiß JC, Andus T, Buderus S, Ehlert U, Engel M, Enninger A, Fischbach W, Gillessen A, Gschossmann J, Gundling F, Haag S, Helwig U, Hollerbach S, Karaus M, Katschinski M, Krammer H, Kuhlbusch-Zicklam R, Matthes H, Menge D, Miehlke S, Posovszky MC, Schaefert R, Schmidt-Choudhury A, Schwandner O, Schweinlin A, Seidl H, Stengel A, Tesarz J, van der Voort I, Voderholzer W, von Boyen G, von Schönfeld J, Wedel T. Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021 – AWMF-Registriernummer: 021/016. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:1323-1415. [PMID: 34891206 DOI: 10.1055/a-1591-4794] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- P Layer
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - V Andresen
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - H Allescher
- Zentrum für Innere Medizin, Gastroent., Hepatologie u. Stoffwechsel, Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, Deutschland
| | - S C Bischoff
- Institut für Ernährungsmedizin, Universität Hohenheim, Stuttgart, Deutschland
| | - M Claßen
- Klinik für Kinder- und Jugendmedizin, Klinikum Links der Weser, Bremen, Deutschland
| | - S Elsenbruch
- Klinik für Neurologie, Translational Pain Research Unit, Universitätsklinikum Essen, Essen, Deutschland.,Abteilung für Medizinische Psychologie und Medizinische Soziologie, Ruhr-Universität Bochum, Bochum, Deutschland
| | - M Freitag
- Abteilung Allgemeinmedizin Department für Versorgungsforschung, Universität Oldenburg, Oldenburg, Deutschland
| | - T Frieling
- Medizinische Klinik II, Helios Klinikum Krefeld, Krefeld, Deutschland
| | - M Gebhard
- Gemeinschaftspraxis Pathologie-Hamburg, Hamburg, Deutschland
| | - M Goebel-Stengel
- Innere Medizin II, Helios Klinik Rottweil, Rottweil, und Innere Medizin VI, Psychosomat. Medizin u. Psychotherapie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - W Häuser
- Innere Medizin I mit Schwerpunkt Gastroenterologie, Klinikum Saarbrücken, Saarbrücken, Deutschland
| | - G Holtmann
- Faculty of Medicine & Faculty of Health & Behavioural Sciences, Princess Alexandra Hospital, Brisbane, Australien
| | - J Keller
- Medizinische Klinik, Israelitisches Krankenhaus, Hamburg, Deutschland
| | - M E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
| | | | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Deutschland
| | - P Lynen Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten, Berlin, Deutschland
| | - A Madisch
- Klinik für Gastroenterologie, interventionelle Endoskopie und Diabetologie, Klinikum Siloah, Klinikum Region Hannover, Hannover, Deutschland
| | - H Mönnikes
- Klinik für Innere Medizin, Martin-Luther-Krankenhaus, Berlin, Deutschland
| | | | - B Niesler
- Abteilung Molekulare Humangenetik Institut für Humangenetik, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - C Pehl
- Medizinische Klinik, Krankenhaus Vilsbiburg, Vilsbiburg, Deutschland
| | - D Pohl
- Klinik für Gastroenterologie und Hepatologie, Universitätsspital Zürich, Zürich, Schweiz
| | - M Raithel
- Medizinische Klinik II m.S. Gastroenterologie und Onkologie, Waldkrankenhaus St. Marien, Erlangen, Deutschland
| | | | - M Schemann
- Lehrstuhl für Humanbiologie, TU München, Deutschland
| | - S Schmiedel
- I. Medizinische Klinik und Poliklinik Gastroenterologie, Universitätsklinikum Hamburg-Eppendorf, Deutschland
| | - J Schwille-Kiuntke
- Abteilung für Psychosomatische Medizin und Psychotherapie, Medizinische Universitätsklinik Tübingen, Tübingen, Deutschland.,Institut für Arbeitsmedizin, Sozialmedizin und Versorgungsforschung, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - M Storr
- Zentrum für Endoskopie, Gesundheitszentrum Starnberger See, Starnberg, Deutschland
| | - J C Preiß
- Klinik für Innere Medizin - Gastroenterologie, Diabetologie und Hepatologie, Vivantes Klinikum Neukölln, Berlin, Deutschland
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28
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Guo F, Cai D, Li Y, Gu H, Qu H, Zong Q, Bao W, Chen A, Liu HY. How Early-Life Gut Microbiota Alteration Sets Trajectories for Health and Inflammatory Bowel Disease? Front Nutr 2021; 8:690073. [PMID: 34422881 PMCID: PMC8377158 DOI: 10.3389/fnut.2021.690073] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 07/05/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a recurrent chronic inflammatory condition of the intestine without any efficient therapeutic regimens. Gut microbiota, which plays an instrumental role in the development and maturation of the immune system, has been implicated in the pathogenesis of IBD. Emerging evidence has established that early-life events particularly maternal influences and antibiotic treatment are strongly correlated with the health or susceptibility to disease of an individual in later life. Thus, it is proposed that there is a critical period in infancy, during which the environmental exposures bestow a long-term pathophysiological imprint. This notion sheds new light on the development of novel approaches for the treatment, i.e., early interventions, more precisely, the prevention of many uncurable chronic inflammatory diseases like IBD. In this review, we have integrated current evidence to describe the feasibility of the "able-to-be-regulated microbiota," summarized the underlying mechanisms of the "microbiota-driven immune system education," explored the optimal intervention time window, and discussed the potential of designing early-probiotic treatment as a new prevention strategy for IBD.
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Affiliation(s)
- Feilong Guo
- Epigenetics and Epigenome Research Institute, Yangzhou University, Yangzhou, China
- Department of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China
- Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
| | - Demin Cai
- Epigenetics and Epigenome Research Institute, Yangzhou University, Yangzhou, China
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Yanwei Li
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Haotian Gu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Huan Qu
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Qiufang Zong
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Wenbin Bao
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
| | - Aoxue Chen
- Department of Psychiatry and Psychotherapy, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
| | - Hao-Yu Liu
- Epigenetics and Epigenome Research Institute, Yangzhou University, Yangzhou, China
- College of Animal Science and Technology, Yangzhou University, Yangzhou, China
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29
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The Effect of Bifidobacterium on Reducing Symptomatic Abdominal Pain in Patients with Irritable Bowel Syndrome: A Systematic Review. Probiotics Antimicrob Proteins 2021; 12:834-839. [PMID: 31741311 PMCID: PMC7456408 DOI: 10.1007/s12602-019-09609-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Probiotics, specifically Bifidobacteria, may improve abdominal pain in patients with irritable bowel syndrome (IBS); however, results from randomised controlled trials (RCTs) are conflicting. Here, we systematically reviewed the efficacy of Bifidobacteria on abdominal pain in IBS. We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to 20 May 2019, without language or date restrictions. The search strategy comprised of the combination of three concepts: supplementation, abdominal pain, and IBS. Inclusion criteria included double-blind placebo-controlled RCTs featuring Bifidobacteria supplementation in Rome-diagnosed IBS patients. A total of 8 RCTs involving a total of 1045 patients with Rome diagnosed IBS were included. The dose of total Bifidobacteria ranged from 106 to > 1011 cfu (colony-forming unit) and duration of supplementation ranged between 2 and 8 weeks. Bifidobacteria was delivered through either intake of fermented milk products, encapsulation or via a malted milk beverage, with all studies assessing abdominal pain via a visual analogue Likert scale. From the studies included, 50% (n = 4) of studies found a statistically significant improvement in abdominal pain following Bifidobacteria supplementation compared to placebo, 38% (n = 3) of studies found non-significant improvements and 12% (n = 1) showed a statistically significant dose-response effect of improvement. The evidence shows a heterogeneity of effect for Bifidobacteria dependent upon strain, dosage and delivery method. While not all studies demonstrate significant improvements in abdominal pain, none of the selected studies reported an increase in pain or other adverse effects.
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30
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Horigome A, Hisata K, Odamaki T, Iwabuchi N, Xiao JZ, Shimizu T. Colonization of Supplemented Bifidobacterium breve M-16V in Low Birth Weight Infants and Its Effects on Their Gut Microbiota Weeks Post-administration. Front Microbiol 2021; 12:610080. [PMID: 33897631 PMCID: PMC8058467 DOI: 10.3389/fmicb.2021.610080] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 03/17/2021] [Indexed: 12/12/2022] Open
Abstract
The colonization and persistence of probiotics introduced into the adult human gut appears to be limited. It is uncertain, however, whether probiotics can successfully colonize the intestinal tracts of full-term and premature infants. In this study, we investigated the colonization and the effect of oral supplementation with Bifidobacterium breve M-16V on the gut microbiota of low birth weight (LBW) infants. A total of 22 LBW infants (12 infants in the M-16V group and 10 infants in the control group) were enrolled. B. breve M-16V was administrated to LBW infants in the M-16V group from birth until hospital discharge. Fecal samples were collected from each subject at weeks (3.7-9.3 weeks in the M-16V group and 2.1-6.1 weeks in the control group) after discharge. qPCR analysis showed that the administrated strain was detected in 83.3% of fecal samples in the M-16V group (at log10 8.33 ± 0.99 cell numbers per gram of wet feces), suggesting that this strain colonized most of the infants beyond several weeks post-administration. Fecal microbiota analysis by 16S rRNA gene sequencing showed that the abundance of Actinobacteria was significantly higher (P < 0.01), whereas that of Proteobacteria was significantly lower (P < 0.001) in the M-16V group as compared with the control group. Notably, the levels of the administrated strain and indigenous Bifidobacterium bacteria were both significantly higher in the M-16V group than in the control group. Our findings suggest that oral administration of B. breve M-16V led to engraftment for at least several weeks post-administration and we observed a potential overall improvement in microbiota formation in the LBW infants' guts.
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Affiliation(s)
- Ayako Horigome
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Ken Hisata
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Toshitaka Odamaki
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Noriyuki Iwabuchi
- Food Ingredients and Technology Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Jin-Zhong Xiao
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
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31
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Yousuf EI, Carvalho M, Dizzell SE, Kim S, Gunn E, Twiss J, Giglia L, Stuart C, Hutton EK, Morrison KM, Stearns JC. Persistence of Suspected Probiotic Organisms in Preterm Infant Gut Microbiota Weeks After Probiotic Supplementation in the NICU. Front Microbiol 2020; 11:574137. [PMID: 33117319 PMCID: PMC7552907 DOI: 10.3389/fmicb.2020.574137] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 08/26/2020] [Indexed: 12/12/2022] Open
Abstract
Probiotics are becoming a prevalent supplement to prevent necrotizing enterocolitis in infants born preterm. However, little is known about the ability of these live bacterial supplements to colonize the gut or how they affect endogenous bacterial strains and the overall gut community. We capitalized on a natural experiment resulting from a policy change that introduced the use of probiotics to preterm infants in a single Neonatal Intensive Care Unit. We used amplicon sequence variants (ASVs) derived from the v3 region of the 16S rRNA gene to compare the prevalence and abundance of Bifidobacterium and Lactobacillus in the gut of preterm infants who were and were not exposed to a probiotic supplement in-hospital. Infants were followed to 5 months corrected age. In the probiotic-exposed infants, ASVs belonging to species of Bifidobacterium appeared at high relative abundance during probiotic supplementation and persisted for up to 5 months. In regression models that controlled for the confounding effects of age and antibiotic exposure, probiotic-exposed infants had a higher abundance of the suspected probiotic bifidobacteria than unexposed infants. Conversely, the relative abundance of Lactobacillus was similar between preterm groups over time. Lactobacillus abundance was inversely related to antibiotic exposure. Furthermore, the overall gut microbial community of the probiotic-exposed preterm infants at term corrected age clustered more closely to samples collected from 10-day old full-term infants than to samples from unexposed preterm infants at term age. In conclusion, routine in-hospital administration of probiotics to preterm infants resulted in the potential for colonization of the gut with probiotic organisms post-discharge and effects on the gut microbiome as a whole. Further research is needed to fully discriminate probiotic bacterial strains from endogenous strains and to explore their functional role in the gut microbiome and in infant health.
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Affiliation(s)
- Efrah I Yousuf
- Department of Pediatrics, McMaster University, Hamilton, ON, Canada.,Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada
| | - Marilia Carvalho
- Department of Obstetrics & Gynecology, McMaster University, Hamilton, ON, Canada
| | - Sara E Dizzell
- Department of Obstetrics & Gynecology, McMaster University, Hamilton, ON, Canada
| | - Stephanie Kim
- Department of Pediatrics, McMaster University, Hamilton, ON, Canada.,Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada
| | - Elizabeth Gunn
- Department of Pediatrics, McMaster University, Hamilton, ON, Canada.,Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada
| | - Jennifer Twiss
- Department of Pediatrics, Division of Neonatology, McMaster University, Hamilton, ON, Canada
| | - Lucy Giglia
- Department of Pediatrics, McMaster University, Hamilton, ON, Canada
| | - Connie Stuart
- Neonatal Follow Up Clinic, McMaster Children's Hospital, Hamilton, ON, Canada
| | - Eileen K Hutton
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada.,Department of Obstetrics & Gynecology, McMaster University, Hamilton, ON, Canada
| | - Katherine M Morrison
- Department of Pediatrics, McMaster University, Hamilton, ON, Canada.,Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada
| | - Jennifer C Stearns
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada.,Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
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32
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Li B, Liang L, Deng H, Guo J, Shu H, Zhang L. Efficacy and Safety of Probiotics in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis. Front Pharmacol 2020; 11:332. [PMID: 32317962 PMCID: PMC7147251 DOI: 10.3389/fphar.2020.00332] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Accepted: 03/06/2020] [Indexed: 12/12/2022] Open
Abstract
Background Irritable bowel syndrome is a functional gastrointestinal disease. Evidence has suggested that probiotics may benefit IBS symptoms. However, clinical trials remain conflicting. Aims To implement a systematic review and meta-analysis of clinical trials regarding the efficacy and safety of probiotics for IBS patients. Methods We searched for relevant trials in Medline(1966 to Jan 2019), Embase(1974 to Jan 2019), the Cochrane Central Register of Controlled Trials(up to Jan 2019), the ClinicalTrials.gov trials register(up to Jan 2019), and Chinese Biomedical Literature Database(1978 to Jan 2019). Risk ratio (RR) and a 95% confidence interval (CI) were calculated for dichotomous outcomes. Standardized mean difference (SMD) and 95% CI were calculated for continuous outcomes. Results A total of 59 studies, including 6,761 patients, were obtained. The RR of the improvement or response with probiotics versus placebo was 1.52 (95% CI 1.32-1.76), with significant heterogeneity (I2 = 71%, P < 0.001). The SMD of Probiotics in improving global IBS symptoms vs. Placebo was -1.8(95% CI -0.30 to -0.06), with significant heterogeneity (I2 = 65%, P < 0.001). It was impossible to draw a determinate conclusion. However, there were differences in subgroup analyses of probiotics type, dose, treatment duration, and geographic position. Probiotics seem to be safe by the analysis of adverse events(RR = 1.07; 95% CI 0.92-1.24; I2 = 0, P = 0.83). Conclusion Probiotics are effective and safe for IBS patients. Single probiotics with a higher dose (daily dose of probiotics ≥1010) and shorter duration (< 8 weeks) seem to be a better choice, but it still needs more trials to prove it.
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Affiliation(s)
- Bing Li
- Department of Pharmacy, 960th Hospital of the PLA, Jinan, China
| | - Li Liang
- Department of Pharmacy, 960th Hospital of the PLA, Jinan, China
| | - Huijie Deng
- Department of Pharmacy, 960th Hospital of the PLA, Jinan, China
| | - Jinmin Guo
- Department of Pharmacy, 960th Hospital of the PLA, Jinan, China
| | - He Shu
- Department of Pharmacy, 960th Hospital of the PLA, Jinan, China
| | - Li Zhang
- Department of Pharmacy, 960th Hospital of the PLA, Jinan, China
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33
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Gao R, Zhang X, Huang L, Shen R, Qin H. Gut Microbiota Alteration After Long-Term Consumption of Probiotics in the Elderly. Probiotics Antimicrob Proteins 2020. [PMID: 29520675 DOI: 10.1007/s12602-018-9403-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gut microbiota has been proven to be of crucial importance in maintaining human health. However, the microbiota profile changes with aging, while the loss of microbiota diversity and the alterations in the optimal composition and quantity of beneficial microbes are believed to increase the risk of many diseases. Although the short-term modulatory impact of probiotics on gut microbiota has been revealed in various studies, no studies focused on longer time consumption of probiotics have been demonstrated. In this study, we found that microbial diversity in the probiotic group was similar to that in the control. We identified a panel of microbiota changes, such as Blautia (10.24 vs. 3.76%, P = 0.006), Streptococcus (7.38 vs. 1.16%, P = 0.004), and Enterococcus (0.13 vs. 0.00%, P = 0.030) were more abundant in the probiotic group. Faecalibacterium, a genus containing anti-inflammatory property, also had a higher abundance in the probiotic group in the gut. The microbiota architecture in the different probiotic dose groups was also revealed. No statistical difference was observed in regard to the short-chain fatty acid concentration between the groups. High-dose intake of probiotics resulted in lower microbial richness. The profile of inflammatory factors indicated that only the level of IL-1β was higher in the probiotic population. Taken together, our study demonstrated that the long-time intake of probiotics caused significant changes in the gut microbiota structure, including an increase in the composition of beneficial microorganisms, which might contribute to the maintenance of host health and homeostasis of microenvironment. More prospective cohorts were needed to illustrate the influences of probiotics on the gut microbiota.
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Affiliation(s)
- Renyuan Gao
- Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China.,Research Institute of Intestinal Diseases, Tongji University School of Medicine, Shanghai, China
| | - Xiaohui Zhang
- Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China.,Research Institute of Intestinal Diseases, Tongji University School of Medicine, Shanghai, China.,Medical College of Soochow University, Suzhou, China
| | - Linsheng Huang
- Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China.,Research Institute of Intestinal Diseases, Tongji University School of Medicine, Shanghai, China
| | - Rongrong Shen
- Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China
| | - Huanlong Qin
- Tenth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China. .,Research Institute of Intestinal Diseases, Tongji University School of Medicine, Shanghai, China. .,Medical College of Soochow University, Suzhou, China.
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34
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Quigley EM. Nutraceuticals as modulators of gut microbiota: Role in therapy. Br J Pharmacol 2020; 177:1351-1362. [PMID: 31659751 PMCID: PMC7056471 DOI: 10.1111/bph.14902] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 09/26/2019] [Accepted: 09/27/2019] [Indexed: 12/12/2022] Open
Abstract
As our knowledge of the various roles of the gut microbiota in the maintenance of homeostasis grows and as we learn how a disrupted microbiota may contribute to disease, therapeutic strategies that target our microbial fellow-travellers become ever more attractive. Most appealing are those interventions that seek to modify or supplement our diet through the addition of nutraceuticals. We now know that our diet, whether in the short or long term, is a major modifier of microbiota composition and function. Of the various nutraceuticals, two categories, prebiotics and probiotics, have received the greatest attention in basic research and product development. While our understanding of the impacts of prebiotics and probiotics on the indigenous microbiota and host biology have been described in great detail in vitro and in animal models, the clinical literature leaves much to be desired. While many claims have been made, few are supported by high quality clinical trials. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.
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Affiliation(s)
- Eamonn M.M. Quigley
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and HepatologyHouston Methodist HospitalHoustonTexas
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35
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Jana T, Acker BW, Cash BD. Probiotics and prebiotics, including fibers and medicinal foods. CLINICAL AND BASIC NEUROGASTROENTEROLOGY AND MOTILITY 2020:587-600. [DOI: 10.1016/b978-0-12-813037-7.00042-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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36
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Herndon CC, Wang YP, Lu CL. Targeting the gut microbiota for the treatment of irritable bowel syndrome. Kaohsiung J Med Sci 2019; 36:160-170. [PMID: 31782606 DOI: 10.1002/kjm2.12154] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Accepted: 10/20/2019] [Indexed: 12/15/2022] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of people across the world. IBS patients are one of the largest subgroups seen in gastroenterology clinics, exhibit a lesser quality of life, and take greater use of the healthcare system. The exact etiology of IBS remains uncertain. Alterations in the gut microbiome may characterize apotential mechanism in the pathogenesis of IBS. This hypothesis is paralleled by rodent models in which manipulation of the gut microbiota leads to disturbed physiological functions along the brain-gut axis. Recent research in IBS treatments has redirected its focus towards gu microbiome based therapeutics. In this review, we discuss potential roles of enteric bacteria in the pathogenesis of IBS and its comorbidities. We then explore the manipulation of the enteric microbiota by prebiotics, probiotics, antibiotics, dietary changes, and fecal microbiota transfer. We also discuss the positive and negative effects of these therapeutics on IBS symptoms.
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Affiliation(s)
- Charles C Herndon
- Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress and Resilience, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Yen-Po Wang
- Institute of Brain Science, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ching-Liang Lu
- Institute of Brain Science, Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.,Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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37
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Suez J, Zmora N, Segal E, Elinav E. The pros, cons, and many unknowns of probiotics. Nat Med 2019; 25:716-729. [DOI: 10.1038/s41591-019-0439-x] [Citation(s) in RCA: 786] [Impact Index Per Article: 131.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 03/28/2019] [Indexed: 02/07/2023]
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38
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Abstract
Technological developments, including massively parallel DNA sequencing, gnotobiotics, metabolomics, RNA sequencing and culturomics, have markedly propelled the field of microbiome research in recent years. These methodologies can be harnessed to improve our in-depth mechanistic understanding of basic concepts related to consumption of probiotics, including their rules of engagement with the indigenous microbiome and impacts on the human host. We have recently demonstrated that even during probiotic supplementation, resident gut bacteria in a subset of individuals resist the mucosal presence of probiotic strains, limiting their modulatory effect on the microbiome and on the host gut transcriptional landscape. Resistance is partly alleviated by antibiotics treatment, which enables probiotics to interact with the host at the gut mucosal interface, although rather than promoting reconstitution of the indigenous microbiome and of the host transcriptional profile, they inhibit these components from returning to their naïve pre-antibiotic configurations. In this commentary, we discuss our findings in the context of previous and recent works, and suggest that incorporating the state-of-the-art methods currently utilized in microbiome research into the field of probiotics may lead to improved understanding of their mechanisms of activity, as well as their efficacy and long-term safety.
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Affiliation(s)
- Jotham Suez
- Immunology Department, Weizmann Institute of Science, Rehovot, Israel
| | - Niv Zmora
- Immunology Department, Weizmann Institute of Science, Rehovot, Israel,Digestive Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel,Internal Medicine Department, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Eran Elinav
- Immunology Department, Weizmann Institute of Science, Rehovot, Israel,Cancer-Microbiome Research Division, DKFZ, Heidelberg, Germany,CONTACT Eran Elinav Immunology Department, Weizmann Institute of Science, 234 Herzl Street, Rehovot 7610001, Israel
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39
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Ling Z, Liu X, Guo S, Cheng Y, Shao L, Guan D, Cui X, Yang M, Xu X. Role of Probiotics in Mycoplasma pneumoniae Pneumonia in Children: A Short-Term Pilot Project. Front Microbiol 2019; 9:3261. [PMID: 30687259 PMCID: PMC6334620 DOI: 10.3389/fmicb.2018.03261] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 12/14/2018] [Indexed: 12/12/2022] Open
Abstract
Mycoplasma pneumoniae is one of the most common pathogens causing community-acquired pneumonia in children. Mycoplasma pneumoniae pneumonia (MPP) can be successfully treated with azithromycin; however, antibiotic-associated diarrhea (AAD) is a common adverse effect. Increasing evidence suggests that some probiotics may prevent the development of AAD. The present study determined the effects of probiotics (live Clostridium butyricum plus Bifidobacterium infantis) on the prevention and treatment of AAD in children with MPP when co-administered with intravenous azithromycin. Fifty-five children with MPP were enrolled and received azithromycin (10 mg/kg/day; once daily for 7 days) combined with probiotics (starting on the third day of azithromycin treatment; 1,500 mg three times daily); 50 healthy children served as controls. At the end of the trial, the incidence of AAD, fecal microbiota, intestinal mucosal barriers, and systemic inflammation were analyzed using recommended systems biology techniques. No cases of AAD or other adverse events occurred in children with MPP after co-administration of probiotics with azithromycin. A live C. butyricum plus B. infantis preparation partly reconstructed the gut microbiota, especially restoration of bacterial diversity. The indicators of intestinal mucosal barrier function, such as D-lactate, endotoxin, and diamine oxidase, were significantly improved and the systemic inflammation (interleukin 10) was attenuated after probiotic therapy. The present study indicated that co-administration of probiotics with azithromycin is a promising therapy for MPP treatment which could prevent and treat AAD effectively.
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Affiliation(s)
- Zongxin Ling
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Xia Liu
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Shu Guo
- Department of Gastroenterology, Affiliated Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Yiwen Cheng
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Li Shao
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Dexiu Guan
- Department of Gastroenterology, Affiliated Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Xiaoshuang Cui
- Department of Gastroenterology, Affiliated Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Mingming Yang
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
| | - Xiwei Xu
- Department of Gastroenterology, Affiliated Beijing Children's Hospital, Capital Medical University, Beijing, China
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40
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Quigley EMM. Prebiotics and Probiotics in Digestive Health. Clin Gastroenterol Hepatol 2019; 17:333-344. [PMID: 30267869 DOI: 10.1016/j.cgh.2018.09.028] [Citation(s) in RCA: 206] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 09/19/2018] [Accepted: 09/20/2018] [Indexed: 02/07/2023]
Abstract
As the importance of the gut microbiota in health and disease is increasingly recognized interest in interventions that can modulate the microbiota and its interactions with its host has soared. Apart from diet, prebiotics and probiotics represent the most commonly used substances taken in an effort to sustain a healthy microbiome or restore balance when it is believed bacterial homeostasis has been disturbed in disease. While a considerable volume of basic science attests to the ability of various prebiotic molecules and probiotic strains to beneficially influence host immune responses, metabolic processes and neuro-endocrine pathways, the evidence base from human studies leaves much to be desired. This translational gap owes much to the manner in which this sector is regulated but also speaks to the challenges that confront the investigator who seeks to explore microbiota modulation in either healthy populations or those who suffer from common digestive ailments. For many products marketed as probiotics, some of the most fundamental issues relating to quality control, such as characterization, formulation, viability safety are scarcely addressed.
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Affiliation(s)
- Eamonn M M Quigley
- Division of Gastroenterology and Hepatology, Lynda K. and David M. Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas.
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41
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Synthetic gutomics: Deciphering the microbial code for futuristic diagnosis and personalized medicine. METHODS IN MICROBIOLOGY 2019. [DOI: 10.1016/bs.mim.2019.02.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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42
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Personalized Gut Mucosal Colonization Resistance to Empiric Probiotics Is Associated with Unique Host and Microbiome Features. Cell 2018; 174:1388-1405.e21. [DOI: 10.1016/j.cell.2018.08.041] [Citation(s) in RCA: 725] [Impact Index Per Article: 103.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2016] [Revised: 06/05/2018] [Accepted: 08/20/2018] [Indexed: 12/17/2022]
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43
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Giron F, Quigley EMM. Pharmabiotic Manipulation of the Microbiota in Gastrointestinal Disorders: A Clinical Perspective. J Neurogastroenterol Motil 2018; 24:355-366. [PMID: 29684976 PMCID: PMC6034666 DOI: 10.5056/jnm18004] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Revised: 03/04/2018] [Accepted: 03/26/2018] [Indexed: 12/13/2022] Open
Abstract
The advent and widespread availability of high-throughput technology has revolutionized the assessment of the communities of microorganisms that inhabit the gastrointestinal tract––the gut microbiota. As our understanding of the role of the microbiota in health and human disease increases, so also do efforts to prevent and treat disease through the modulation of the microbiota. Several strategies are available to us and range from time honored approaches, such as antibiotics and probiotics, to changes in diet, the administration of prebiotics as food supplements, and fecal microbiota transplantation. Of these, diet is perhaps the most pervasive but often ignored modulator of the microbiota, and a failure to recognize its impact complicates the interpretation of many microbiota studies. The impacts of antibiotics on the microbiota are more complex than originally thought and, though antibiotics can be life-saving, their effects on commensal bacterial populations can be clinically significant. Though there have been many studies of, and even more claims made for, probiotics, the majority of available studies suffer from significant deficits in study design and execution and many claims remain to be substantiated. Though holding much promise, the study of prebiotics in human disease is still in its infancy. Possibilities other than the administration of live organisms have been identified through efforts to mine the microbiota for novel therapeutics and include: dead organisms, bacterial components, small molecules elaborated by bacteria, and even bacterial DNA. Accordingly, the term pharmabiotic has been introduced to encompass the full range of therapeutic possibilities that the microbiota offers.
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Affiliation(s)
- Fanny Giron
- Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA
| | - Eamonn M M Quigley
- Gastroenterology and Hepatology, Lynda K and David M Underwood Center for Digestive Disorders, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas, USA
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44
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Skrypnik K, Suliburska J. Association between the gut microbiota and mineral metabolism. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2018; 98:2449-2460. [PMID: 28991359 DOI: 10.1002/jsfa.8724] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 08/23/2017] [Accepted: 09/27/2017] [Indexed: 06/07/2023]
Abstract
The aim of this review is to present the most recent scientific evidence of interactions between the intestinal microbiota and minerals, and the effect of this interaction on the health of the host. The Web of Science database from the years 2013-2017 on this topic was reviewed. Numerous in vitro studies have shown that iron significantly affects the intestinal microbiota. However, Bifidobacteriaceae are capable of binding iron in the large intestine, thereby limiting the formation of free radicals synthesized in the presence of iron, and thus reducing the risk of colorectal cancer. Animal studies have revealed that supplementation with probiotics, prebiotics and synbiotics has a significant effect on bone calcium, phosphate and bone metabolism. The dynamic interaction between microbiota and zinc was shown. Human studies have provided evidence of the influence of probiotic bacteria on parathormone, calcium and phosphate levels and thus on bone resorption. Recent studies have produced new information mainly on the impact of the intestinal bacteria on the metabolism of calcium and iron. From a scientific perspective, the most urgent fields that remain to be investigated are the identification of all human gut microbes and new therapies targeting the interaction between intestinal bacteria and minerals. © 2017 Society of Chemical Industry.
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Affiliation(s)
- Katarzyna Skrypnik
- Institute of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland
| | - Joanna Suliburska
- Institute of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland
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45
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Enck P, Mazurak N. Dysbiosis in Functional Bowel Disorders. ANNALS OF NUTRITION AND METABOLISM 2018; 72:296-306. [PMID: 29694952 DOI: 10.1159/000488773] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 03/21/2018] [Indexed: 12/12/2022]
Abstract
Functional bowel disorders (FBD) resemble a group of diseases of the gastrointestinal (GI) tract that are without a clear pathogenesis; the best known is probably the "irritable bowel syndrome" (IBS). Only recently we have been able to explore the role of the gut microbiota in FBD due to progress in microbiological analytic techniques. There are different ways to explore the role of the gut microbiota and its dysbiosis in FBD. Comparison of the microbial composition in a group of patients with FBD, for example, with IBS to a group of healthy volunteers is one way. Studies have shown that the microbiota in FBD is different from that of healthy controls, but the recorded differences are not necessarily specific for FBD, they may also occur in other diseases. Another approach to explore the role of the gut microbiota in FBD is to challenge the existing "flora" with novel bacteria (probiotics) or with nutritional substrates that stimulate bacterial growth (prebiotics). More than 60 such trials including several thousand patients have been performed in IBS. These studies have produced mixed outcome: some probiotics appear to be better than others, and some appear to work only for a part of the IBS symptoms and not for all. An extreme form of this approach is the transfer of an entire microbiota from 1 healthy person to another, called fecal microbiota transplantation. This has rarely been tested in FBD but is not without risk in benign disorders.
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Hungin APS, Mitchell CR, Whorwell P, Mulligan C, Cole O, Agréus L, Fracasso P, Lionis C, Mendive J, Philippart de Foy J, Seifert B, Wensaas K, Winchester C, de Wit N. Systematic review: probiotics in the management of lower gastrointestinal symptoms - an updated evidence-based international consensus. Aliment Pharmacol Ther 2018; 47:1054-1070. [PMID: 29460487 PMCID: PMC5900870 DOI: 10.1111/apt.14539] [Citation(s) in RCA: 84] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Revised: 09/15/2017] [Accepted: 01/05/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND In 2013, a systematic review and Delphi consensus reported that specific probiotics can benefit adult patients with irritable bowel syndrome (IBS) and other gastrointestinal (GI) problems. AIM To update the consensus with new evidence. METHODS A systematic review identified randomised, placebo-controlled trials published between January 2012 and June 2017. Evidence was graded, previously developed statements were reassessed by an 8-expert panel, and agreement was reached via Delphi consensus. RESULTS A total of 70 studies were included (IBS, 34; diarrhoea associated with antibiotics, 13; diarrhoea associated with Helicobacter pylori eradication therapy, 7; other conditions, 16). Of 15 studies that examined global IBS symptoms as a primary endpoint, 8 reported significant benefits of probiotics vs placebo. Consensus statements with 100% agreement and "high" evidence level indicated that specific probiotics help reduce overall symptom burden and abdominal pain in some patients with IBS and duration/intensity of diarrhoea in patients prescribed antibiotics or H. pylori eradication therapy, and have favourable safety. Statements with 70%-100% agreement and "moderate" evidence indicated that, in some patients with IBS, specific probiotics help reduce bloating/distension and improve bowel movement frequency/consistency. CONCLUSIONS This updated review indicates that specific probiotics are beneficial in certain lower GI problems, although many of the new publications did not report benefits of probiotics, possibly due to inclusion of new, less efficacious preparations. Specific probiotics can relieve lower GI symptoms in IBS, prevent diarrhoea associated with antibiotics and H. pylori eradication therapy, and show favourable safety. This study will help clinicians recommend/prescribe probiotics for specific symptoms.
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Kumar K, Saadi M, Ramsey FV, Schey R, Parkman HP. Effect of Bifidobacterium infantis 35624 (Align) on the Lactulose Breath Test for Small Intestinal Bacterial Overgrowth. Dig Dis Sci 2018; 63:989-995. [PMID: 29397491 DOI: 10.1007/s10620-018-4945-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2017] [Accepted: 01/20/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND Small intestinal bacterial overgrowth (SIBO) may cause symptoms in patients with abdominal bloating, distension, and gas. SIBO can be assessed using the lactulose breath test (LBT). A commonly used probiotic supplement is Align containing Bifidobacterium infantis 35624. The aim of this study was to determine the effect of B. infantis 35624 on hydrogen and methane excretion during LBT. METHODS Healthy subjects underwent LBT before and after 2 weeks of daily Align administration. Hydrogen and methane concentrations were measured for each breath sample. Results are expressed as mean ± SE and analyzed using repeated measures ANCOVA. A breath test was considered positive if hydrogen and/or methane increased > 20 ppm above baseline by 90 min of the test or if a dual hydrogen peak was present. RESULTS Nineteen healthy subjects were studied. Hydrogen levels were similar pre- and post-probiotic across the 3-h study (p = 0.768). In contrast, methane levels were significantly higher with probiotic administration (p = 0.012). A rise in methane > 20 ppm was seen in three subjects pre-probiotic but six post-probiotic. Of the 19 subjects, an "abnormal" LBT pre-probiotic was present in ten subjects and during the probiotic, 13 were abnormal. CONCLUSIONS This study found that 2 weeks of B. infantis 35624 (Align) supplementation affects LBT assessment for SIBO by significantly increasing methane, but not hydrogen, excretion after lactulose administration. Methane levels reached values that would be considered positive for SIBO patients. This study suggests that patients undergoing LBT should discontinue probiotics prior to the test as these supplements may alter the test results.
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Affiliation(s)
- Krishma Kumar
- Gastroenterology Section, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Mohammed Saadi
- Gastroenterology Section, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Frederick V Ramsey
- Gastroenterology Section, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Ron Schey
- Gastroenterology Section, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA
| | - Henry P Parkman
- Gastroenterology Section, Department of Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
- Gastroenterology Section, Temple University School of Medicine, 3401 North Broad Street, Philadelphia, PA, 19140, USA.
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Harris LA, Baffy N. Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome. Postgrad Med 2017; 129:872-888. [PMID: 28936910 DOI: 10.1080/00325481.2017.1383819] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Irritable bowel syndrome (IBS), which is characterized by recurrent abdominal pain and disordered bowel habits, is one of the most common functional bowel disorders. IBS is a substantial burden on both patient health-related quality of life and healthcare costs. Several pathophysiologic mechanisms have been postulated for the occurrence of IBS, including altered gastrointestinal motility, visceral hypersensitivity, changes in gut permeability, immune activation, gut-brain dysregulation, central nervous system dysfunction, and changes in the gut microbiota. Of note, both qualitative and quantitative differences have been observed in the gut microbiota of a population with IBS versus a healthy population. Because of the substantial interest in the gut microbiota and its role as a therapeutic target in IBS, this article provides an overview of specific interventions with the potential to modulate the gut microbiota in IBS, including elimination diets, prebiotics, probiotics, synbiotics, and nonsystemic antibiotics. Although probiotics and synbiotics are generally well tolerated, differences in the composition and concentration of different bacterial species and inclusion or exclusion of prebiotic components varies widely across studies and has prevented strong recommendations on their use in IBS. For nonsystemic antibiotics, rifaximin is indicated in the United States for the treatment of IBS with diarrhea in adults and has been shown to be efficacious and well tolerated in well-designed clinical trials. Overall, more consistent evidence is needed regarding the efficacy and safety of elimination diets, prebiotics, probiotics, and synbiotics for the treatment of patients with IBS. Furthermore, additional well-designed studies are needed that examine alterations in the gut microbiota that occur with these interventions and their potential associations with clinical symptoms of IBS.
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Affiliation(s)
- Lucinda A Harris
- a Division of Gastroenterology & Hepatology , Mayo Clinic , Scottsdale , AZ , USA
| | - Noemi Baffy
- a Division of Gastroenterology & Hepatology , Mayo Clinic , Scottsdale , AZ , USA
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Xu X, Jia X, Mo L, Liu C, Zheng L, Yuan Q, Zhou X. Intestinal microbiota: a potential target for the treatment of postmenopausal osteoporosis. Bone Res 2017; 5:17046. [PMID: 28983411 PMCID: PMC5627629 DOI: 10.1038/boneres.2017.46] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2017] [Accepted: 07/24/2017] [Indexed: 02/08/2023] Open
Abstract
Postmenopausal osteoporosis (PMO) is a prevalent metabolic bone disease characterized by bone loss and structural destruction, which increases the risk of fracture in postmenopausal women. Owing to the high morbidity and serious complications of PMO, many efforts have been devoted to its prophylaxis and treatment. The intestinal microbiota is the complex community of microorganisms colonizing the gastrointestinal tract. Probiotics, which are dietary or medical supplements consisting of beneficial intestinal bacteria, work in concert with endogenous intestinal microorganisms to maintain host health. Recent studies have revealed that bone loss in PMO is closely related to host immunity, which is influenced by the intestinal microbiota. The curative effects of probiotics on metabolic bone diseases have also been demonstrated. The effects of the intestinal microbiota on bone metabolism suggest a promising target for PMO management. This review seeks to summarize the critical effects of the intestinal microbiota and probiotics on PMO, with a focus on the molecular mechanisms underlying the pathogenic relationship between bacteria and host, and to define the possible treatment options.
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Affiliation(s)
- Xin Xu
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xiaoyue Jia
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Longyi Mo
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Chengcheng Liu
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Liwei Zheng
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Quan Yuan
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Dental Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Xuedong Zhou
- State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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Browne HP, Neville BA, Forster SC, Lawley TD. Transmission of the gut microbiota: spreading of health. Nat Rev Microbiol 2017; 15:531-543. [PMID: 28603278 PMCID: PMC5837012 DOI: 10.1038/nrmicro.2017.50] [Citation(s) in RCA: 148] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Transmission of commensal intestinal bacteria between humans could promote health by establishing, maintaining and replenishing microbial diversity in the microbiota of an individual. Unlike pathogens, the routes of transmission for commensal bacteria remain unappreciated and poorly understood, despite the likely commonalities between both. Consequently, broad infection control measures that are designed to prevent pathogen transmission and infection, such as oversanitation and the overuse of antibiotics, may inadvertently affect human health by altering normal commensal transmission. In this Review, we discuss the mechanisms and factors that influence host-to-host transmission of the intestinal microbiota and examine how a better understanding of these processes will identify new approaches to nurture and restore transmission routes that are used by beneficial bacteria.
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Affiliation(s)
- Hilary P Browne
- Host-Microbiota Interactions Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK
| | - B Anne Neville
- Host-Microbiota Interactions Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK
| | - Samuel C Forster
- Host-Microbiota Interactions Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK
- Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia
- Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria 3800, Australia
| | - Trevor D Lawley
- Host-Microbiota Interactions Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK
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