|
1
|
Vatn SS, Hansen SH, Tannæs TM, Brackmann S, Olbjørn C, Bergemalm D, Keita ÅV, Gomollon F, Detlie TE, Kalla R, Satsangi J, Jahnsen J, Vatn MH, Halfvarson J, Hov JR, Ricanek P, Moen AEF, On behalf of the IBD-Character Consortium. Microbial Patterns in Newly Diagnosed Inflammatory Bowel Disease Revealed by Presence and Transcriptional Activity - Relationship to Diagnosis and Outcome. Clin Exp Gastroenterol 2025; 18:103-119. [PMID: 40491932 PMCID: PMC12148070 DOI: 10.2147/ceg.s504459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 04/29/2025] [Indexed: 06/11/2025] Open
Abstract
Background As part of the IBD Character initiative, we examined an inception cohort and investigated mucosal microbiota composition and transcriptional activity in relation to clinical outcomes. Methods A cohort of 237 individuals were included from five countries: Crohn's disease (CD, n = 72), ulcerative colitis (UC, n = 57), symptomatic non-IBD controls (SC, n = 78) and healthy controls (HC, n = 30). Rectal/colonic biopsies were obtained at inclusion, and DNA and RNA were extracted from the same biopsy and examined by sequencing the 16S rRNA V4 region. Results Beta diversity measurements separated IBD from both HC and SC. IBD and SC exhibited reduced intra-individual diversity compared with HC. When comparing taxonomy at DNA and RNA level, six bacteria were found to differ in abundance and/or transcriptional activity between IBD and symptomatic control, while there were 14 and three between symptomatic control and CD and UC, respectively. A limited number of bacterial taxa were responsible for the largest difference between presence and activity, separating patients and controls. Multiple bacterial taxa were associated with treatment escalation in both UC and CD. Machine-learning models separated IBD from symptomatic controls and treatment escalators from non-escalators (AUC >0.8). However, the differential effects were mainly driven by clinical biomarkers, such as f-calprotectin, s-albumin, and b-hemoglobin. Conclusion Differences between presence and transcriptional activity were found among multiple taxa when assessing 16S rRNA at DNA and RNA level. Symptomatic controls were more similar to the IBD patients compared to HC. The analyses suggest that the mucosal microbiota carries a moderate diagnostic and predictive potential, outcompeted by f-calprotectin.
Collapse
Affiliation(s)
- Simen Svendsen Vatn
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway
- Innlandet Hospital Trust, Gjøvik, Norway
| | - Simen Hyll Hansen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Norwegian PSC Research Center and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
| | - Tone Møller Tannæs
- Section for Clinical Molecular Biology (Epigen), Akershus University Hospital, Lørenskog, Norway
| | - Stephan Brackmann
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway
| | - Christine Olbjørn
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway
| | - Daniel Bergemalm
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Åsa V Keita
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | | | - Trond Espen Detlie
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway
| | - Rahul Kalla
- Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, Division of Medical and Radiological Sciences, University of Edinburgh, Edinburgh, UK
| | - Jack Satsangi
- Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, Division of Medical and Radiological Sciences, University of Edinburgh, Edinburgh, UK
- Translational Gastroenterology Unit, Medical Sciences/ Experimental Medicine Division, University of Oxford, Oxford, UK
| | - Jørgen Jahnsen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway
| | | | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Johannes Roksund Hov
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Norwegian PSC Research Center and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Petr Ricanek
- Department of Gastroenterology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway
- Department of Gastroenterology, lovisenberg Diaconal Hospital, Oslo, Norway
| | - Aina E F Moen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Section for Clinical Molecular Biology (Epigen), Akershus University Hospital, Lørenskog, Norway
- Department of Virology, Norwegian Institute of Public Health, Oslo, Norway
| | - On behalf of the IBD-Character Consortium
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway
- Innlandet Hospital Trust, Gjøvik, Norway
- Norwegian PSC Research Center and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway
- Section for Clinical Molecular Biology (Epigen), Akershus University Hospital, Lørenskog, Norway
- Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway
- Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
- Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
- Digestive Diseases Unit, IIS Aragón, Zaragoza, Spain
- Gastrointestinal Unit, Centre for Genomics and Molecular Medicine, Division of Medical and Radiological Sciences, University of Edinburgh, Edinburgh, UK
- Translational Gastroenterology Unit, Medical Sciences/ Experimental Medicine Division, University of Oxford, Oxford, UK
- Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Department of Gastroenterology, lovisenberg Diaconal Hospital, Oslo, Norway
- Department of Virology, Norwegian Institute of Public Health, Oslo, Norway
| |
Collapse
|
|
2
|
Alcedo González J, Estremera-Arévalo F, Cobián Malaver J, Santos Vicente J, Alcalá-González LG, Naves J, Barba Orozco E, Barber Caselles C, Serrano-Falcón B, Accarino Garaventa A, Alonso-Cotoner C, Serra Pueyo J. Common questions and rationale answers about the intestinal bacterial overgrowth syndrome (SIBO). GASTROENTEROLOGIA Y HEPATOLOGIA 2025; 48:502216. [PMID: 38852778 DOI: 10.1016/j.gastrohep.2024.502216] [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: 03/28/2024] [Revised: 05/15/2024] [Accepted: 05/24/2024] [Indexed: 06/11/2024]
Abstract
The recognition and treatment of intestinal bacterial overgrowth syndrome are matters of controversy. The symptoms that have guided the search for the disorder suffer from lack of specificity, especially in the absence of well-defined predisposing factors. The accuracy of diagnostic procedures has been questioned and the proposed therapies achieve generally low effectiveness figures, with large differences between available studies. It is also unknown whether the normalization of tests is really a guarantee of cure. Within this framework of uncertainty, and in order to contribute to the guidance and homogenization of medical practice, a group of experts from the AEG and ASENEM have formulated the key questions on the management of this pathology and have provided answers to them, in accordance with the available scientific evidence. In addition, they have drawn up statements based on the conclusions of the review and have voted on them individually to reflect the degree of consensus for each statement.
Collapse
Affiliation(s)
- Javier Alcedo González
- Servicio de Aparato Digestivo, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, España.
| | - Fermín Estremera-Arévalo
- Servicio de Aparato Digestivo, Hospital Universitario de Navarra, Navarrabiomed, Universidad Pública de Navarra - IdiSNA, Navarra, España
| | | | - Javier Santos Vicente
- Laboratorio de Neuro-Inmuno-Gastroenterología, Unidad de Investigación de Aparato Digestivo, Institut de Recerca (VHIR), Servicio de Aparato Digestivo, Hospital Universitario Vall d'Hebron, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Instituto de Salud Carlos III, Madrid, España
| | | | - Juan Naves
- Servicio de Aparato Digestivo, Hospital del Mar, Barcelona, España
| | - Elizabeth Barba Orozco
- Unidad de Neurogastroenterología y Motilidad, Hospital Clínic de Barcelona, Barcelona, España; Departamento de Gastroenterología, Universidad de Barcelona, Barcelona, España
| | | | - Blanca Serrano-Falcón
- Servicio de Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada, España
| | | | - Carmen Alonso-Cotoner
- Laboratorio de Neuro-Inmuno-Gastroenterología, Unidad de Investigación de Aparato Digestivo, Institut de Recerca (VHIR), Servicio de Aparato Digestivo, Hospital Universitario Vall d'Hebron, Barcelona, España; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Instituto de Salud Carlos III, Madrid, España; Facultad de Medicina, Universidad Autónoma de Barcelona, Barcelona, España
| | - Jordi Serra Pueyo
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Instituto de Salud Carlos III, Madrid, España; Área de Aparato Digestivo, Hospital Universitario Vall d'Hebron, Barcelona, España
| |
Collapse
|
|
3
|
Rahkola EN, Rautava S, Hiltunen H, Ross C, Lahti L, Isolauri E. The preterm gut microbiota and administration routes of different probiotics: a randomized controlled trial. Pediatr Res 2023; 94:1480-1487. [PMID: 37020105 PMCID: PMC10589095 DOI: 10.1038/s41390-023-02560-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 02/09/2023] [Accepted: 02/14/2023] [Indexed: 04/07/2023]
Abstract
BACKGROUND Preterm children with their aberrant gut microbiota and susceptibility to infections and inflammation constitute a considerable target group for probiotic therapy to generate the age-appropriate healthy microbiota. METHODS 68 preterm neonates were randomized into five intervention groups: Beginning from the median age of 3 days, 13 children received Lactobacillus rhamnosus GG (LGG) directly orally, and 17 via the lactating mother. 14 children received LGG with Bifidobacterium lactis Bb-12 (Bb12) orally, and 10 via the lactating mother. 14 children received placebo. The children's faecal microbiota was assessed at the age of 7 days by 16S rRNA gene sequencing. RESULTS The gut microbiota compositions of the children directly receiving the probiotic combination (LGG + Bb12) were significantly different from those of the children receiving the other intervention modes or placebo (p = 0.0012; PERMANOVA), the distinction being due to an increase in the relative abundance of Bifidobacterium animalis (P < 0.00010; ANCOM-BC), and the order Lactobacillales (P = 0.020; ANCOM-BC). CONCLUSION The connection between aberrant primary gut microbiota and a heightened risk of infectious and non-communicable diseases invites effective microbiota modulation. We show that the direct, early, and brief probiotic intervention of LGG + Bb12 109 CFU each, is sufficient to modulate the gut microbiota of the preterm neonate. IMPACT Preterm children have a higher risk of several health problems partly due to their aberrant gut microbiota. More research is needed to find a safe probiotic intervention to modify the gut microbiota of preterm children. The maternal administration route via breast milk might be safer for the newborn. In our study, the early and direct administration of the probiotic combination Lactobacillus rhamnosus GG with Bifidobacterium lactis Bb-12 increased the proportion of bifidobacteria in the preterm children's gut at the age of 7 days, but the maternal administration route was not as effective.
Collapse
Affiliation(s)
- Ella-Noora Rahkola
- Department of Clinical Sciences, Faculty of Medicine, University of Turku, Turku, Finland.
- Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland.
| | - Samuli Rautava
- Department of Clinical Sciences, Faculty of Medicine, University of Turku, Turku, Finland
- Department of Pediatrics, University of Helsinki and Children's Hospital, Helsinki University Hospital, Helsinki, Finland
| | - Henni Hiltunen
- Department of Clinical Sciences, Faculty of Medicine, University of Turku, Turku, Finland
- Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland
| | - Chandler Ross
- Department of Computing, University of Turku, Turku, Finland
| | - Leo Lahti
- Department of Computing, University of Turku, Turku, Finland
| | - Erika Isolauri
- Department of Clinical Sciences, Faculty of Medicine, University of Turku, Turku, Finland
- Department of Paediatrics and Adolescent Medicine, Turku University Hospital, Turku, Finland
| |
Collapse
|
|
4
|
Sutera AM, Arfuso F, Tardiolo G, Riggio V, Fazio F, Aiese Cigliano R, Paytuví A, Piccione G, Zumbo A. Effect of a Co-Feed Liquid Whey-Integrated Diet on Crossbred Pigs' Fecal Microbiota. Animals (Basel) 2023; 13:1750. [PMID: 37889679 PMCID: PMC10252047 DOI: 10.3390/ani13111750] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/17/2023] [Accepted: 05/23/2023] [Indexed: 07/30/2023] Open
Abstract
This study assessed the potential effect of a co-feed liquid whey-integrated diet on the fecal microbiota of 14 crossbred pigs. The experimental design was as follows: seven pigs were in the control group, fed with a control feed, and seven were in the experimental group, fed with the same control feed supplemented daily with liquid whey. The collection of fecal samples was conducted on each animal before the dietary treatment (T0) and one (T1), and two (T2) months after the beginning of the co-feed integration. In addition, blood samples were collected from each pig at the same time points in order to evaluate the physiological parameters. Taxonomic analysis showed a bacterial community dominated by Firmicutes, Bacteroidetes, Spirochaetes, and Proteobacteria phyla that populated the crossbred pig feces. The diversity metrics suggested that the co-feed supplementation affected some alpha diversity indexes of the fecal microbiota. In addition, the differential abundance analysis at the genus level revealed significant differences for various genera, suggesting that the liquid whey supplementation potentially influenced a part of the bacterial community over time. Spearman's correlations revealed that the differential abundant genera identified are positively or negatively correlated with the physiological parameters.
Collapse
Affiliation(s)
- Anna Maria Sutera
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell’Annunziata, Via Palatucci snc, 98168 Messina, Italy; (A.M.S.); (F.A.); (F.F.); (G.P.); (A.Z.)
| | - Francesca Arfuso
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell’Annunziata, Via Palatucci snc, 98168 Messina, Italy; (A.M.S.); (F.A.); (F.F.); (G.P.); (A.Z.)
| | - Giuseppe Tardiolo
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell’Annunziata, Via Palatucci snc, 98168 Messina, Italy; (A.M.S.); (F.A.); (F.F.); (G.P.); (A.Z.)
| | - Valentina Riggio
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush Campus, Edinburgh EH25 9RG, UK;
| | - Francesco Fazio
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell’Annunziata, Via Palatucci snc, 98168 Messina, Italy; (A.M.S.); (F.A.); (F.F.); (G.P.); (A.Z.)
| | | | - Andreu Paytuví
- Sequentia Biotech SL, Carrer del Dr. Trueta 179, 08005 Barcelona, Spain; (R.A.C.); (A.P.)
| | - Giuseppe Piccione
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell’Annunziata, Via Palatucci snc, 98168 Messina, Italy; (A.M.S.); (F.A.); (F.F.); (G.P.); (A.Z.)
| | - Alessandro Zumbo
- Department of Veterinary Sciences, University of Messina, Polo Universitario dell’Annunziata, Via Palatucci snc, 98168 Messina, Italy; (A.M.S.); (F.A.); (F.F.); (G.P.); (A.Z.)
| |
Collapse
|
|
5
|
Chan S, Hawley CM, Pascoe EM, Cao C, Campbell KL, Campbell SB, Francis RS, Hale R, Isbel NM, Morrison M, Johnson DW. PREBIOTIC: a study protocol of a randomised controlled trial to assess prebiotic supplementation in kidney transplant recipients for preventing infections and gastrointestinal upset - a feasibility study. Pilot Feasibility Stud 2023; 9:11. [PMID: 36647175 PMCID: PMC9841639 DOI: 10.1186/s40814-023-01236-y] [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: 01/13/2021] [Accepted: 01/02/2023] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Modulating the microbiota in the large intestine of kidney transplant recipients through prebiotic supplementation may prevent infectious complications from occurring. To date, there have been no interventional trials which have investigated this novel treatment in kidney transplantation. The aim of PREBIOTIC is to assess the feasibility of performing a randomised controlled trial of prebiotics in reducing infections and gastrointestinal symptoms in kidney transplant recipients. METHODS Sixty kidney transplant patients will be recruited to a double-blind, placebo-controlled, randomised feasibility trial. Patients will be provided with prebiotic therapy or placebo for 4 to 6 weeks. Outcomes will include recruitment, adherence, tolerance, retention, laboratory parameters (including serum indoxyl sulphate, ρ-cresyl sulphate and stool collection), patients' self-assessed quality of life, gastrointestinal symptoms and clinical outcomes. DISCUSSION This trial will assess the feasibility of prebiotic supplementation in kidney transplant recipients. Prebiotics not only may alter the gut microbiota and their inherent metabolism and production of uraemic toxins but also may prevent infections from occurring in kidney transplant recipients. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry number ACTRN12618001057279p. The date of registration was 25th June 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375370&isReview=true .
Collapse
Affiliation(s)
- Samuel Chan
- grid.412744.00000 0004 0380 2017Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Queensland Australia ,grid.1003.20000 0000 9320 7537Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland Australia ,grid.489335.00000000406180938Translational Research Institute, Brisbane, Queensland Australia
| | - Carmel M. Hawley
- grid.412744.00000 0004 0380 2017Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Queensland Australia ,grid.1003.20000 0000 9320 7537Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland Australia ,grid.489335.00000000406180938Translational Research Institute, Brisbane, Queensland Australia
| | - Elaine M. Pascoe
- grid.412744.00000 0004 0380 2017Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Queensland Australia ,grid.1003.20000 0000 9320 7537Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland Australia ,grid.489335.00000000406180938Translational Research Institute, Brisbane, Queensland Australia
| | - Christopher Cao
- grid.412744.00000 0004 0380 2017Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Queensland Australia
| | - Katrina L. Campbell
- grid.1003.20000 0000 9320 7537Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland Australia
| | - Scott B. Campbell
- grid.412744.00000 0004 0380 2017Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Queensland Australia ,grid.1003.20000 0000 9320 7537Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland Australia ,grid.489335.00000000406180938Translational Research Institute, Brisbane, Queensland Australia
| | - Ross S. Francis
- grid.412744.00000 0004 0380 2017Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Queensland Australia ,grid.1003.20000 0000 9320 7537Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland Australia ,grid.489335.00000000406180938Translational Research Institute, Brisbane, Queensland Australia
| | - Rachael Hale
- grid.412744.00000 0004 0380 2017Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Queensland Australia
| | - Nicole M. Isbel
- grid.412744.00000 0004 0380 2017Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Queensland Australia ,grid.1003.20000 0000 9320 7537Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland Australia ,grid.489335.00000000406180938Translational Research Institute, Brisbane, Queensland Australia
| | - Mark Morrison
- grid.1003.20000 0000 9320 7537The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Woolloongabba, Queensland Australia
| | - David W. Johnson
- grid.412744.00000 0004 0380 2017Department of Nephrology, Princess Alexandra Hospital, Woolloongabba, Queensland Australia ,grid.1003.20000 0000 9320 7537Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland Australia ,grid.489335.00000000406180938Translational Research Institute, Brisbane, Queensland Australia
| |
Collapse
|
|
6
|
Yang Z, Xu F, Li H, He Y. Beyond samples: A metric revealing more connections of gut microbiota between individuals. Comput Struct Biotechnol J 2021; 19:3930-3937. [PMID: 34377361 PMCID: PMC8319210 DOI: 10.1016/j.csbj.2021.07.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 07/03/2021] [Accepted: 07/07/2021] [Indexed: 10/31/2022] Open
Abstract
Studies of gut microbiota explore their complicated connections between individuals of different characteristics by applying different metrics to abundance data obtained from fecal samples. Although classic metrics are capable to quantify differences between samples, the microbiome of fecal sample is not a good surrogate for the gut microbiome of individuals because the microbial populations of the distal colon does not adequately represent that of the entire gastrointestinal tract. To overcome the deficiency of classic metrics in which the differences can be measured between the samples analyzed, but not the corresponding populations, we propose a metric for representing composition differences in the gut microbiota of individuals. Our investigation shows this metric outperforms traditional measures for multiple scenarios. For gut microbiota in diverse geographic populations, this metric presents more explainable data variance than others, not only in regular variance analysis but also in principle component analysis and partition analysis of biologic characteristics. With time-series data, the metric further presents a strong correlation with the time interval of serial sampling. Our findings suggest that the metric is robust and powerfully detects the intrinsic variations in gut microbiota. The metric holds promise for revealing more relations between gut microbiota and human health.
Collapse
Affiliation(s)
- Zhen Yang
- Shanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
| | - Feng Xu
- Shanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
| | - Hongdou Li
- Obstetrics Gynecology Hospital, The Institute of Reproduction and Developmental Biology, Fudan University, Shanghai, China
| | - Yungang He
- Shanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
| |
Collapse
|
|
7
|
Soopramanien M, Khan NA, Siddiqui R. Gut microbiota of animals living in polluted environments are a potential resource of anticancer molecules. J Appl Microbiol 2021; 131:1039-1055. [PMID: 33368930 DOI: 10.1111/jam.14981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 12/09/2020] [Accepted: 12/21/2020] [Indexed: 12/17/2022]
Abstract
Cancer is a prominent cause of morbidity and mortality worldwide, in spite of advances in therapeutic interventions and supportive care. In 2018 alone, there were 18·1 million new cancer cases and 9·6 million deaths indicating the need for novel anticancer agents. Plant-based products have often been linked with protective effects against communicable and non-communicable diseases. Recently, we have shown that animals such as crocodiles thrive in polluted environments and are often exposed to carcinogenic agents, but still benefit from prolonged lifespan. The protective mechanisms shielding them from cancer could be attributed to the immune system, and/or it is possible that their gut microbiota produce anticancer molecules. In support, several lines of evidence suggest that gut microbiota plays a critical role in the physiology of its host. Here, we reviewed the available literature to assess whether the gut microbiota of animals thriving in polluted environment possess anticancer molecules.
Collapse
Affiliation(s)
- M Soopramanien
- Department of Biological Sciences, Sunway University, Bandar Sunway, Malaysia
| | - N A Khan
- Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - R Siddiqui
- College of Arts and Sciences, American University of Sharjah, University City, Sharjah, United Arab Emirates
| |
Collapse
|
|
8
|
Bojović K, Ignjatović ÐDI, Soković Bajić S, Vojnović Milutinović D, Tomić M, Golić N, Tolinački M. Gut Microbiota Dysbiosis Associated With Altered Production of Short Chain Fatty Acids in Children With Neurodevelopmental Disorders. Front Cell Infect Microbiol 2020; 10:223. [PMID: 32509596 PMCID: PMC7248180 DOI: 10.3389/fcimb.2020.00223] [Citation(s) in RCA: 109] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 04/22/2020] [Indexed: 12/20/2022] Open
Abstract
While gut microbiota dysbiosis has been linked with autism, its role in the etiology of other neurodevelopmental disorders (NDD) is largely underexplored. To our knowledge this is the first study to evaluate gut microbiota diversity and composition in 36 children from the Republic of Serbia diagnosed with NDD and 28 healthy children. The results revealed an increased incidence of potentially harmful bacteria, closely related to Clostridium species, in the NDD patient group compared to the Control group: Desulfotomaculum guttoideum (P < 0.01), Intestinibacter bartlettii (P < 0.05), and Romboutsia ilealis (P < 0.001). On the other hand, significantly lower diversity of common commensal bacteria in the NDD group of patients was noticed. Enterococcus faecalis (P < 0.05), Enterococcus gallinarum (P < 0.01), Streptococcus pasteurianus (P < 0.05), Lactobacillus rhamnosus (P < 0.01) and Bifidobacteria sp. were detected in lower numbers of patients or were even absent in some NDD patients. In addition, butyrate-producing bacteria Faecalibacterium prausnitzii (P < 0.01), Butyricicoccus pullicaecorum (P < 0.05), and Eubacterium rectale (P = 0.07) were less frequent in the NDD patient group. In line with that, the levels of fecal short chain fatty acids (SCFAs) were determined. Although significant differences in SCFA levels were not detected between NDD patients and the Control group, a positive correlation was noted between number of rDNA amplicons obtained with universal primers and level of propionic acid, as well as a trend for levels of total SCFAs and butyric acid in the Control group. This correlation is lost in the NDD patient group, indicating that NDD patients' microbiota differs from the microbiota of healthy children in the presence or number of strong SCFA-producing bacteria. According to a range-weighted richness index it was observed that microbial diversity was significantly lower in the NDD patient group. Our study reveals that the intestinal microbiota from NDD patients differs from the microbiota of healthy children. It is hypothesized that early life microbiome might have an impact on GI disturbances and accompanied behavioral problems frequently observed in patients with a broad spectrum of NDD.
Collapse
Affiliation(s)
| | - Ður -d ica Ignjatović
- Department of Biochemistry, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
- *Correspondence: Ðurđica Ignjatović
| | - Svetlana Soković Bajić
- Laboratory for Molecular Microbiology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Danijela Vojnović Milutinović
- Department of Biochemistry, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
| | - Mirko Tomić
- Department of Biochemistry, Institute for Biological Research “Siniša Stanković”, University of Belgrade, Belgrade, Serbia
| | - Nataša Golić
- Laboratory for Molecular Microbiology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
| | - Maja Tolinački
- Laboratory for Molecular Microbiology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
- Maja Tolinački
| |
Collapse
|
|
9
|
Chan S, Isbel NM, Hawley CM, Campbell SB, Campbell KL, Morrison M, Francis RS, Playford EG, Johnson DW. Infectious Complications Following Kidney Transplantation-A Focus on Hepatitis C Infection, Cytomegalovirus Infection and Novel Developments in the Gut Microbiota. ACTA ACUST UNITED AC 2019; 55:medicina55100672. [PMID: 31590269 PMCID: PMC6843315 DOI: 10.3390/medicina55100672] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 09/24/2019] [Accepted: 09/30/2019] [Indexed: 12/19/2022]
Abstract
The incidence of infectious complications, compared with the general population and the pre-transplant status of the recipient, increases substantially following kidney transplantation, causing significant morbidity and mortality. The potent immunosuppressive therapy given to prevent graft rejection in kidney transplant recipients results in an increased susceptibility to a wide range of opportunistic infections including bacterial, viral and fungal infections. Over the last five years, several advances have occurred that may have changed the burden of infectious complications in kidney transplant recipients. Due to the availability of direct-acting antivirals to manage donor-derived hepatitis C infection, this has opened the way for donors with hepatitis C infection to be considered in the donation process. In addition, there have been the development of medications targeting the growing burden of resistant cytomegalovirus, as well as the discovery of the potentially important role of the gastrointestinal microbiota in the pathogenesis of post-transplant infection. In this narrative review, we will discuss these three advances and their potential implications for clinical practice.
Collapse
Affiliation(s)
- Samuel Chan
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
- Correspondence: ; Tel.: +61-7-3176-5080
| | - Nicole M Isbel
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
| | - Carmel M Hawley
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
| | - Scott B Campbell
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
| | - Katrina L Campbell
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Centre for Applied Health Economics, Menzies Research Institute, Griffith University, Brisbane, QLD 4102, Australia
| | - Mark Morrison
- The University of Queensland Diamantina Institute, Faculty of Medicine, University of Queensland, Woolloongabba, QLD 4102, Australia;
| | - Ross S Francis
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
| | - E Geoffrey Playford
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Infection Management Services, Department of Microbiology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia
| | - David W Johnson
- Department of Nephrology, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia; (N.M.I.); (C.M.H.); (S.B.C.); (R.S.F.); (D.W.J.)
- Australasian Kidney Trials Network, The University of Queensland, Brisbane, QLD 4102, Australia; (K.L.C.); (E.G.P.)
- Translational Research Institute, Brisbane, QLD 4102, Australia
| |
Collapse
|
|
10
|
Mangifesta M, Mancabelli L, Milani C, Gaiani F, de'Angelis N, de'Angelis GL, van Sinderen D, Ventura M, Turroni F. Mucosal microbiota of intestinal polyps reveals putative biomarkers of colorectal cancer. Sci Rep 2018; 8:13974. [PMID: 30228361 PMCID: PMC6143603 DOI: 10.1038/s41598-018-32413-2] [Citation(s) in RCA: 151] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 08/29/2018] [Indexed: 02/07/2023] Open
Abstract
The human intestine retains a complex microbial ecosystem, which performs crucial functions that impact on host health. Several studies have indicated that intestinal dysbiosis may impact on the establishment of life-threatening intestinal diseases such as colorectal cancer. An adenomatous polyp is the result of abnormal tissue growth, which is benign but is considered to be associated with a high risk of developing colorectal cancer, based on its grade of dysplasia. Development of diagnostic tools that are based on surveying the gut microbiota and are aimed at early detection of colorectal cancer represent highly desirable target. For this purpose, we performed a pilot study in which we applied a metataxonomic analysis based on 16S rRNA gene sequencing approach to unveil the composition of microbial communities of intestinal polyps. Moreover, we performed a meta-analysis involving the reconstructed microbiota composition of adenomatous polyps and publicly available metagenomics datasets of colorectal cancer. These analyses allowed the identification of microbial taxa such as Faecalibacterium, Bacteroides and Romboutsia, which appear to be depleted in cancerogenic mucosa as well as in adenomatous polyps, thus representing novel microbial biomarkers associated with early tumor formation. Furthermore, an absolute quantification of Fusubacterium nucleatum in polyps further compounded the important role of this microorganism as a valuable putative microbial biomarker for early diagnosis of colorectal cancer.
Collapse
Affiliation(s)
- Marta Mangifesta
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Leonardo Mancabelli
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Christian Milani
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Federica Gaiani
- Gastroenterology and Endoscopy Unit, University Hospital of Parma, Parma, Italy
| | - Nicola de'Angelis
- Department of HPB Surgery and Liver Transplantation, Henri-Mondor Hospital, Université Paris Est-UPEC, Créteil, France
| | | | - Douwe van Sinderen
- School of Microbiology & APC Microbiome Institute, University College Cork, Cork, Ireland
| | - Marco Ventura
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
- Microbiome Research Hub, University of Parma, Parma, Italy
| | - Francesca Turroni
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
- Microbiome Research Hub, University of Parma, Parma, Italy.
| |
Collapse
|
|
11
|
Borgo F, Garbossa S, Riva A, Severgnini M, Luigiano C, Benetti A, Pontiroli AE, Morace G, Borghi E. Body Mass Index and Sex Affect Diverse Microbial Niches within the Gut. Front Microbiol 2018; 9:213. [PMID: 29491857 PMCID: PMC5817072 DOI: 10.3389/fmicb.2018.00213] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Accepted: 01/30/2018] [Indexed: 12/12/2022] Open
Abstract
Gut microbiota is considered a separate organ with endocrine capabilities, actively contributing to tissue homeostasis. It consists of at least two separate microbial populations, the lumen-associated (LAM) and the mucosa-associated microbiota (MAM). In the present study, we compared LAM and MAM, by collecting stools and sigmoid brush samples of forty adults without large-bowel symptoms, and through a 16S rRNA gene next-generation sequencing (NGS) approach. MAM sample analysis revealed enrichment in aerotolerant Proteobacteria, probably selected by a gradient of oxygen that decreases from tissue to lumen, and in Streptococcus and Clostridium spp., highly fermenting bacteria. On the other hand, LAM microbiota showed an increased abundance in Bacteroides, Prevotella, and Oscillospira, genera able to digest and to degrade biopolymers in the large intestine. Predicted metagenomic analysis showed LAM to be enriched in genes encoding enzymes mostly involved in energy extraction from carbohydrates and lipids, whereas MAM in amino acid and vitamin metabolism. Moreover, LAM and MAM communities seemed to be influenced by different host factors, such as diet and sex. LAM is affected by body mass index (BMI) status. Indeed, BMI negatively correlates with Faecalibacterium prausnitzii and Flavonifractor plautii abundance, putative biomarkers of healthy status. In contrast, MAM microbial population showed a significant grouping according to sex. Female MAM was enriched in Actinobacteria (with an increased trend of the genus Bifidobacterium), and a significant depletion in Veillonellaceae. Interestingly, we found the species Gemmiger formicilis to be associated with male and Bifidobacterium adolescentis, with female MAM samples. In conclusion, our results suggest that gut harbors microbial niches that differ in both composition and host factor susceptibility, and their richness and diversity may be overlooked evaluating only fecal samples.
Collapse
Affiliation(s)
- Francesca Borgo
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | | | - Alessandra Riva
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.,Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Research Network "Chemistry meets Microbiology", University of Vienna, Vienna, Austria
| | - Marco Severgnini
- Institute of Biomedical Technologies, National Research Council, Segrate, Italy
| | | | | | - Antonio E Pontiroli
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.,ASST Santi Paolo e Carlo Hospital, Milan, Italy
| | - Giulia Morace
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| | - Elisa Borghi
- Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
| |
Collapse
|
|
12
|
Barko P, McMichael M, Swanson K, Williams D. The Gastrointestinal Microbiome: A Review. J Vet Intern Med 2018; 32:9-25. [PMID: 29171095 PMCID: PMC5787212 DOI: 10.1111/jvim.14875] [Citation(s) in RCA: 410] [Impact Index Per Article: 58.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 08/30/2017] [Accepted: 10/12/2017] [Indexed: 12/14/2022] Open
Abstract
The gastrointestinal microbiome is a diverse consortium of bacteria, archaea, fungi, protozoa, and viruses that inhabit the gut of all mammals. Studies in humans and other mammals have implicated the microbiome in a range of physiologic processes that are vital to host health including energy homeostasis, metabolism, gut epithelial health, immunologic activity, and neurobehavioral development. The microbial genome confers metabolic capabilities exceeding those of the host organism alone, making the gut microbiome an active participant in host physiology. Recent advances in DNA sequencing technology and computational biology have revolutionized the field of microbiomics, permitting mechanistic evaluation of the relationships between an animal and its microbial symbionts. Changes in the gastrointestinal microbiome are associated with diseases in humans and animals including inflammatory bowel disease, asthma, obesity, metabolic syndrome, cardiovascular disease, immune-mediated conditions, and neurodevelopmental conditions such as autism spectrum disorder. While there remains a paucity of data regarding the intestinal microbiome in small animals, recent studies have helped to characterize its role in host animal health and associated disease states. This review is intended to familiarize small animal veterinarians with recent advances in the field of microbiomics and to prime them for a future in which diagnostic tests and therapies will incorporate these developments into clinical practice.
Collapse
Affiliation(s)
- P.C. Barko
- Veterinary Clinical MedicineUniversity of Illinois at Urbana‐ChampaignUrbanaIL
| | - M.A. McMichael
- Veterinary Clinical MedicineUniversity of Illinois at Urbana‐ChampaignUrbanaIL
| | - K.S. Swanson
- Veterinary Clinical MedicineUniversity of Illinois at Urbana‐ChampaignUrbanaIL
- Department of Animal SciencesUniversity of Illinois at Urbana‐ChampaignUrbanaIL
| | - D.A. Williams
- Veterinary Clinical MedicineUniversity of Illinois at Urbana‐ChampaignUrbanaIL
| |
Collapse
|
|
13
|
Abstract
Host-microbe interactions are influenced by complex host genetics and environment. Studies across animal taxa have aided our understanding of how intestinal microbiota influence vertebrate development, disease, and physiology. However, traditional mammalian studies can be limited by the use of isogenic strains, husbandry constraints that result in small sample sizes and limited statistical power, reliance on indirect characterization of gut microbial communities from fecal samples, and concerns of whether observations in artificial conditions are actually reflective of what occurs in the wild. Fish models are able to overcome many of these limitations. The extensive variation in the physiology, ecology, and natural history of fish enriches studies of the evolution and ecology of host-microbe interactions. They share physiological and immunological features common among vertebrates, including humans, and harbor complex gut microbiota, which allows identification of the mechanisms driving microbial community assembly. Their accelerated life cycles and large clutch sizes and the ease of sampling both internal and external microbial communities make them particularly well suited for robust statistical studies of microbial diversity. Gnotobiotic techniques, genetic manipulation of the microbiota and host, and transparent juveniles enable novel insights into mechanisms underlying development of the digestive tract and disease states. Many diseases involve a complex combination of genes which are difficult to manipulate in homogeneous model organisms. By taking advantage of the natural genetic variation found in wild fish populations, as well as of the availability of powerful genetic tools, future studies should be able to identify conserved genes and pathways that contribute to human genetic diseases characterized by dysbiosis.
Collapse
Affiliation(s)
- Emily A Lescak
- University of Alaska Anchorage, Department of Biological Sciences, Anchorage, Alaska, USA
| | | |
Collapse
|
|
14
|
Millares L, Bermudo G, Pérez-Brocal V, Domingo C, Garcia-Nuñez M, Pomares X, Moya A, Monsó E. The respiratory microbiome in bronchial mucosa and secretions from severe IgE-mediated asthma patients. BMC Microbiol 2017; 17:20. [PMID: 28103814 PMCID: PMC5248442 DOI: 10.1186/s12866-017-0933-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 01/13/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The bronchial microbiome in chronic lung diseases presents an abnormal pattern, but its microbial composition and regional differences in severe asthma have not been sufficiently addressed. The aim of the study was to describe the bacterial community in bronchial mucosa and secretions of patients with severe chronic asthma chronically treated with corticosteroids in addition to usual care according to Global Initiative for Asthma. Bacterial community composition was obtained by 16S rRNA gene amplification and sequencing, and functional capabilities through PICRUSt. RESULTS Thirteen patients with severe asthma were included and provided 11 bronchial biopsies (BB) and 12 bronchial aspirates (BA) suitable for sequence analyses. Bacteroidetes, Firmicutes, Proteobacteria and Actinobacteria showed relative abundances (RAs) over 5% in BB, a cutoff that was reached by Streptococcus and Prevotella at genus level. Legionella genus attained a median RA of 2.7 (interquartile range 1.1-4.7) in BB samples. In BA a higher RA of Fusobacteria was found, when compared with BB [8.7 (5.9-11.4) vs 4.2 (0.8-7.5), p = 0.037], while the RA of Proteobacteria was lower in BA [4.3 (3.7-6.5) vs 17.1 (11.2-33.4), p = 0.005]. RA of the Legionella genus was also significantly lower in BA [0.004 (0.001-0.02) vs. 2.7 (1.1-4.7), p = 0.005]. Beta-diversity analysis confirmed the differences between the microbial communities in BA and BB (R2 = 0.20, p = 0.001, Adonis test), and functional analysis revealed also statistically significant differences between both types of sample on Metabolism, Cellular processes, Human diseases, Organismal systems and Genetic information processing pathways. CONCLUSIONS The microbiota in the bronchial mucosa of severe asthma has a specific pattern that is not accurately represented in bronchial secretions, which must be considered a different niche of bacteria growth.
Collapse
Affiliation(s)
- Laura Millares
- Fundació Parc Taulí, Parc Taulí 1, Edificio Santa Fe, planta baja, 08208, Sabadell, Barcelona, Spain.
- CIBER de Enfermedades Respiratorias, CIBERES, Madrid, Spain.
- Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, Spain.
- Fundació Insitut d'Investigació Germans Trias i Pujol, Badalona, Spain.
| | - Guadalupe Bermudo
- Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - Vicente Pérez-Brocal
- Genomics and Health Area, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Public Health), Valencia, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Evolutionary Genetics Unit, Institut Cavanilles de Biodiversitat i Biologia Evolutiva (ICBiBE), Universitat de València, Valencia, Spain
| | - Christian Domingo
- Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain
- Department of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Marian Garcia-Nuñez
- Fundació Parc Taulí, Parc Taulí 1, Edificio Santa Fe, planta baja, 08208, Sabadell, Barcelona, Spain
- CIBER de Enfermedades Respiratorias, CIBERES, Madrid, Spain
- Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, Spain
- Fundació Insitut d'Investigació Germans Trias i Pujol, Badalona, Spain
| | - Xavier Pomares
- Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain
| | - Andrés Moya
- Genomics and Health Area, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunidad Valenciana (FISABIO-Public Health), Valencia, Spain
- CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Evolutionary Genetics Unit, Institut Cavanilles de Biodiversitat i Biologia Evolutiva (ICBiBE), Universitat de València, Valencia, Spain
| | - Eduard Monsó
- CIBER de Enfermedades Respiratorias, CIBERES, Madrid, Spain
- Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, Spain
- Department of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| |
Collapse
|
|
15
|
Allen-Blevins CR, You X, Hinde K, Sela DA. Handling stress may confound murine gut microbiota studies. PeerJ 2017; 5:e2876. [PMID: 28097073 PMCID: PMC5234434 DOI: 10.7717/peerj.2876] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 12/07/2016] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO), the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis), a species sensitive to host stress (Bailey & Coe, 2004). Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. METHODS This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS) solution or deionized, distilled water. Gastrointestinal (GI) tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR) was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and Firmicutes. RESULTS Our results demonstrate a significant difference between the amount of Firmicutes in pups receiving water passively and those receiving FOS actively (p-value = 0.009). Additionally, we found significant differences between the fecal microbiota from handled and non-handled mouse pups. DISCUSSION From our results, we conclude even handling pups for experimental purposes, without gavage, may induce enough stress to alter the murine gut microbiota profile. We suggest further studies to examine potential stress effects on gut microbiota caused by experimental techniques. Stress from experimental techniques may need to be accounted for in future gut microbiota studies.
Collapse
Affiliation(s)
- Cary R. Allen-Blevins
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, United States
| | - Xiaomeng You
- Department of Food Science, University of Massachusetts, Amherst, MA, United States
| | - Katie Hinde
- Center for Evolution and Medicine, Arizona State University, Tempe, AZ, United States
- School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, United States
| | - David A. Sela
- Department of Food Science, University of Massachusetts, Amherst, MA, United States
- Department of Microbiology, University of Massachusetts, Amherst, MA, United States
- Center for Microbiome Research, University of Massachusetts Medical School, Worcester, MA, United States
| |
Collapse
|
|
16
|
Watt E, Gemmell MR, Berry S, Glaire M, Farquharson F, Louis P, Murray GI, El-Omar E, Hold GL. Extending colonic mucosal microbiome analysis-assessment of colonic lavage as a proxy for endoscopic colonic biopsies. MICROBIOME 2016; 4:61. [PMID: 27884202 PMCID: PMC5123352 DOI: 10.1186/s40168-016-0207-9] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 11/07/2016] [Indexed: 05/11/2023]
Abstract
BACKGROUND Sequencing-based analysis has become a well-established approach to deciphering the composition of the gut microbiota. However, due to the complexity of accessing sufficient material from colonoscopic biopsy samples, most studies have focused on faecal microbiota analysis, even though it is recognised that differences exist between the microbial composition of colonic biopsies and faecal samples. We determined the suitability of colonic lavage samples to see if it had comparable microbial diversity composition to colonic biopsies as they are without the limitations associated with sample size. We collected paired colonic biopsies and lavage samples from subjects who were attending for colorectal cancer screening colonoscopy. RESULTS Next-generation sequencing and qPCR validation were performed with multiple bioinformatics analyses to determine the composition and predict function of the microbiota. Colonic lavage samples contained significantly higher numbers of operational taxonomic units (OTUs) compared to corresponding biopsy samples, however, diversity and evenness between lavage and biopsy samples were similar. The differences seen were driven by the presence of 12 OTUs which were in higher relative abundance in biopsies and were either not present or in low relative abundance in lavage samples, whilst a further 3 OTUs were present in higher amounts in the lavage samples compared to biopsy samples. However, predicted functional community profiling based on 16S ribosomal ribonucleic acid (rRNA) data indicated minimal differences between sample types. CONCLUSIONS We propose that colonic lavage samples provide a relatively accurate representation of biopsy microbiota composition and should be considered where biopsy size is an issue.
Collapse
Affiliation(s)
- Euan Watt
- Gastrointestinal Research Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Matthew R. Gemmell
- Centre for Genome Enabled Biology and Medicine, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Susan Berry
- Gastrointestinal Research Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Mark Glaire
- Gastrointestinal Research Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Freda Farquharson
- Rowett Institute of Nutrition and Health, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Petra Louis
- Rowett Institute of Nutrition and Health, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Graeme I. Murray
- Department of Pathology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD UK
| | - Emad El-Omar
- Gastrointestinal Research Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD UK
- St George and Sutherland Clinical School, University of New South Wales, St George Hospital, Short Street, Kogarah, Sydney, NSW 2217 Australia
| | - Georgina L. Hold
- Gastrointestinal Research Group, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, AB25 2ZD UK
| |
Collapse
|
|
17
|
Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease. Sci Rep 2016; 6:36797. [PMID: 27827438 PMCID: PMC5101533 DOI: 10.1038/srep36797] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 10/21/2016] [Indexed: 12/26/2022] Open
Abstract
A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation. However, for practical reasons, these reports have primarily analysed the faecal microbiota. In the present investigation, we have assessed, for the first time, the changes in the microbiota at the site of infection by a parasitic helminth (hookworm) and gluten-dependent inflammation in humans with CeD using biopsy tissue from the duodenum. Hookworm infection and gluten exposure were associated with an increased abundance of species
within the Bacteroides phylum, as well as increases in the richness and diversity of the tissue-resident microbiota within the intestine, results that are consistent with previous reports using other helminth species in humans and animal models. Hence, this may represent a mechanism by which parasitic helminths may restore intestinal immune homeostasis and exert a therapeutic benefit in CeD, and potentially other inflammatory disorders.
Collapse
|
|
18
|
Liu Y, Zhang L, Wang X, Wang Z, Zhang J, Jiang R, Wang X, Wang K, Liu Z, Xia Z, Xu Z, Nie Y, Lv X, Wu X, Zhu H, Duan L. Similar Fecal Microbiota Signatures in Patients With Diarrhea-Predominant Irritable Bowel Syndrome and Patients With Depression. Clin Gastroenterol Hepatol 2016; 14:1602-1611.e5. [PMID: 27266978 DOI: 10.1016/j.cgh.2016.05.033] [Citation(s) in RCA: 216] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2016] [Revised: 04/13/2016] [Accepted: 05/10/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with irritable bowel syndrome (IBS) often have psychiatric comorbidities. Alterations in the intestinal microbiota have been associated with IBS and depression, but it is not clear if there is a microbial relationship between these disorders. We studied the profiles of fecal microbiota samples from patients with IBS, depression, or comorbidities of IBS and depression; we determined the relationships among these profiles and clinical and pathophysiological features of these disorders. METHODS We used 454 pyrosequencing to analyze fecal microbiota samples from 100 subjects (40 with diarrhea-predominant IBS [IBS-D], 15 with depression, 25 with comorbidities of IBS and depression, and 20 healthy individuals [controls]), recruited at Peking University. Abdominal and psychological symptoms were evaluated with validated questionnaires. Visceral sensitivity was evaluated using a barostat. Colonic mucosal inflammation was assayed by immunohistochemical analyses of sigmoid tissue biopsy specimens. RESULTS Fecal microbiota signatures were similar between patients with IBS-D and depression in that they were less diverse than samples from controls and had similar abundances of alterations. They were characterized by high proportions of Bacteroides (type I), Prevotella (type II), or nondominant microbiota (type III). Most patients with IBS-D or depression had type I or type II profiles (IBS-D had 85% type I and type II profiles, depression had 80% type I and type II profiles). Colon tissues from patients with type I or type II profiles had higher levels of inflammatory markers than colon tissues from patients with type III profiles. The level of colon inflammation correlated with the severity of IBS symptoms. CONCLUSIONS Patients with IBS-D and depression have similar alterations in fecal microbiota; these might be related to the pathogenesis of these disorders. We identified 3 microbial profiles in patients that could indicate different subtypes of IBS and depression or be used as diagnostic biomarkers.
Collapse
Affiliation(s)
- Yixuan Liu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Lu Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xiaoqi Wang
- Department of Biomedical Engineering, Center for Quantitative Biology, College of Engineering, Peking University, Beijing, China
| | - Zhe Wang
- Department of Biomedical Engineering, Center for Quantitative Biology, College of Engineering, Peking University, Beijing, China
| | - Jingjing Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Ronghuan Jiang
- Department of Psychiatry, Institute of Mental Health, Peking University, Beijing, China
| | - Xiangqun Wang
- Department of Psychiatry, Institute of Mental Health, Peking University, Beijing, China
| | - Kun Wang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Zuojing Liu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Zhiwei Xia
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Zhijie Xu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Yong Nie
- Department of Energy and Resources Engineering, College of Engineering, Peking University, Beijing, China
| | - Xianglin Lv
- Department of Energy and Resources Engineering, College of Engineering, Peking University, Beijing, China
| | - Xiaolei Wu
- Department of Energy and Resources Engineering, College of Engineering, Peking University, Beijing, China
| | - Huaiqiu Zhu
- Department of Biomedical Engineering, Center for Quantitative Biology, College of Engineering, Peking University, Beijing, China.
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
| |
Collapse
|
|
19
|
Suzuki TA, Nachman MW. Spatial Heterogeneity of Gut Microbial Composition along the Gastrointestinal Tract in Natural Populations of House Mice. PLoS One 2016; 11:e0163720. [PMID: 27669007 PMCID: PMC5036816 DOI: 10.1371/journal.pone.0163720] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2016] [Accepted: 09/13/2016] [Indexed: 01/15/2023] Open
Abstract
There is a growing appreciation of the role of gut microbial communities in host biology. However, the nature of variation in microbial communities among different segments of the gastrointestinal (GI) tract is not well understood. Here, we describe microbial communities from ten different segments of the GI tract (mouth, esophagus, stomach, duodenum, ileum, proximal cecum, distal cecum, colon, rectum, and feces) in wild house mice using 16S rRNA gene amplicon sequencing. We also measured carbon and nitrogen stable isotopic ratios from hair samples of individual mice as a proxy for diet. We identified factors that may explain differences in microbial composition among gut segments, and we tested for differences among individual mice in the composition of the microbiota. Consistent with previous studies, the lower GI tract was characterized by a greater relative abundance of anaerobic bacteria and greater microbial diversity relative to the upper GI tract. The upper and lower GI tracts also differed in the relative abundances of predicted microbial gene functions, including those involved in metabolic pathways. However, when the upper and lower GI tracts were considered separately, gut microbial composition was associated with individual mice. Finally, microbial communities derived from fecal samples were similar to those derived from the lower GI tract of their respective hosts, supporting the utility of fecal sampling for studying the gut microbiota of mice. These results show that while there is substantial heterogeneity among segments of the GI tract, individual hosts play a significant role in structuring microbial communities within particular segments of the GI tract.
Collapse
Affiliation(s)
- Taichi A. Suzuki
- Department of Integrative Biology, Museum of Vertebrate Zoology, University of California, Berkeley, California, United States of America
- * E-mail:
| | - Michael W. Nachman
- Department of Integrative Biology, Museum of Vertebrate Zoology, University of California, Berkeley, California, United States of America
| |
Collapse
|
|
20
|
Abstract
Consistent interactions between the gut microbiome and adaptive immunity recently led several research groups to evaluate modifications of human gut microbiota composition during HIV infection. Herein we propose to review the shifts reported in infected individuals, as their correlation to disease progression. Though the gut microbiota is consistently altered in HIV individuals, the literature reveals several discrepancies, such as changes in microbial diversity associated with HIV status, taxa modified in infected subjects or influence of ART on gut flora restoration. Similarly, mechanisms involved in interactions between gut bacteria and immunity are to date poorly elucidated, emphasizing the importance of understanding how microbes can promote HIV replication. Further research is needed to propose adjuvant therapeutics dedicated to controlling disease progression through gut microbiome restoration.
Collapse
|
|
21
|
Abstract
Celiac disease (CD) is a common chronic autoimmune enteropathy caused by gluten intake. To date, the only therapy for CD is the complete exclusion of dietary sources of grains and any food containing gluten. It has been hypothesized that the intestinal microbiota is somehow involved in CD. For this reason, probiotics are appearing as an interesting adjuvant in the dietetic management of CD. This review aims to discuss the characteristics of the microbiota in CD subjects and the use of probiotics as a novel therapy for CD. Comparisons between children with CD and controls show that their microbiota profiles differ; the former have fewer lactobacilli and bifidobacteria. Specific probiotics have been found to digest or alter gluten polypeptides. It has also been demonstrated that some bacterial species belonging to the genera Lactobacillus and Bifidobacterium exert protective properties on epithelial cells from damage caused by gliadin.
Collapse
|
|
22
|
Galley JD, Yu Z, Kumar P, Dowd SE, Lyte M, Bailey MT. The structures of the colonic mucosa-associated and luminal microbial communities are distinct and differentially affected by a prolonged murine stressor. Gut Microbes 2014; 5:748-60. [PMID: 25536463 PMCID: PMC4615309 DOI: 10.4161/19490976.2014.972241] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
The commensal microbiota of the human gastrointestinal tract live in a largely stable community structure, assisting in host physiological and immunological functions. Changes to this structure can be injurious to the health of the host, a concept termed dysbiosis. Psychological stress is a factor that has been implicated in causing dysbiosis, and studies performed by our lab have shown that restraint stress can indeed shift the cecal microbiota structure as well as increase the severity of a colonic infection caused by Citrobacter rodentium. However, this study, like many others, have focused on fecal contents when examining the effect of dysbiosis-causing stimuli (e.g. psychological stress) upon the microbiota. Since the mucosa-associated microbiota have unique properties and functions that can act upon the host, it is important to understand how stressor exposure might affect this niche of bacteria. To begin to understand whether chronic restraint stress changes the mucosa-associated and/or luminal microbiota mice underwent 7 16-hour cycles of restraint stress, and the microbiota of both colonic tissue and fecal contents were analyzed by sequencing using next-gen bacterial tag-encoded FLX amplicon technology (bTEFAP) pyrosequencing. Both control and stress groups had significantly different mucosa-associated and luminal microbiota communities, highlighting the importance of focusing gastrointestinal community structure analysis by microbial niche. Furthermore, restraint stress was able to disrupt both the mucosa-associated and luminally-associated colonic microbiota by shifting the relative abundances of multiple groups of bacteria. Among these changes, there was a significant reduction in the immunomodulatory commensal genus Lactobacillus associated with colonic mucosa. The relative abundance of Lactobacillus spp. was not affected in the lumen. These results indicate that stressor-exposure can have distinct effects upon the colonic microbiota situated at the mucosal epithelium in comparison to the luminal-associated microbiota.
Collapse
Affiliation(s)
- Jeffrey D Galley
- Division of Oral Biolog; College of Dentistry; The Ohio State University; Columbus, OH USA
| | - Zhongtang Yu
- Department of Animal Sciences; College of Food; Agricultural and Environmental Sciences; The Ohio State University, Columbus, OH USA
| | - Purnima Kumar
- Division of Periodontology; College of Dentistry; The Ohio State University; Columbus, OH USA
| | - Scot E Dowd
- Research and Testing Laboratory; Lubbock, TX USA
| | - Mark Lyte
- Department of Immunotherapeutics and Biotechnology; School of Pharmacy; Texas Tech University Health Sciences Center; Abilene, TX USA
| | - Michael T Bailey
- Division of Oral Biolog; College of Dentistry; The Ohio State University; Columbus, OH USA,Institute for Behavioral Medicine Research; College of Medicine; The Ohio State University; Columbus, OH USA,Department of Pediatrics; Wexner Medical Center; The Ohio State University; Columbus, OH USA,Correspondence to: Michael T Bailey;
| |
Collapse
|
|
23
|
Giovannini M, Verduci E, Gregori D, Ballali S, Soldi S, Ghisleni D, Riva E. Prebiotic Effect of an Infant Formula Supplemented with Galacto-Oligosaccharides: Randomized Multicenter Trial. J Am Coll Nutr 2014; 33:385-93. [DOI: 10.1080/07315724.2013.878232] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
|
|
24
|
Abstract
Rhubarb is often used to establish chronic diarrhea and spleen (Pi)-deficiency syndrome animal models in China. In this study, we utilized the enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) method to detect changes in bacterial diversity in feces and the bowel mucosa associated with this model. Total microbial genomic DNA from the small bowel (duodenum, jejunum, and ileum), large bowel (proximal colon, distal colon, and rectum), cecum, and feces of normal and rhubarb-exposed rats were used as templates for the ERIC-PCR analysis. We found that the fecal microbial composition did not correspond to the bowel bacteria mix. More bacterial diversity was observed in the ileum of rhubarb-exposed rats (P<0.05). Furthermore, a 380 bp product was found to be increased in rhubarb-exposed rats both in faces and the bowel mucosa. The product was cloned and sequenced and showed high similarity with regions of the Bacteroides genome. AS a result of discriminant analysis with the SPSS software, the Canonical Discriminant Function Formulae for model rats was established.
Collapse
Affiliation(s)
- Ying Peng
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
| | | | | | | |
Collapse
|
|
25
|
Affiliation(s)
- Ying PENG
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
| | - Chunfu WU
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China
| | - Jingyu YANG
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China
| | - Xiaobo LI
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
| |
Collapse
|
|
26
|
Centanni M, Turroni S, Consolandi C, Rampelli S, Peano C, Severgnini M, Biagi E, Caredda G, De Bellis G, Brigidi P, Candela M. The enterocyte-associated intestinal microbiota of breast-fed infants and adults responds differently to a TNF-α-mediated pro-inflammatory stimulus. PLoS One 2013; 8:e81762. [PMID: 24303069 PMCID: PMC3841132 DOI: 10.1371/journal.pone.0081762] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2013] [Accepted: 10/16/2013] [Indexed: 12/20/2022] Open
Abstract
Co-evolved as an integral component of our immune system, the gut microbiota provides specific immunological services at different ages, supporting the immune education during our infancy and sustaining a well-balanced immunological homeostasis during the course of our life. In order to figure out whether this involves differences in the microbial groups primarily interacting with the host immune system, we developed a non-invasive HT29 cell-based minimal model to fingerprint the enterocyte-associated microbiota fraction in infants and adults. After depicting the fecal microbial community of 12 breast-fed infants and 6 adults by 16S rDNA amplicon pools 454 pyrosequencing, their respective HT29 cell-associated gut microbiota fractions were characterized by the universal phylogenetic array platform HTF-Microbi.Array, both in the presence and absence of a tumor necrosis factor-alpha (TNF-α)-mediated pro-inflammatory stimulus. Our data revealed remarkable differences between the enterocyte-associated microbiota fractions in breast-fed infants and adults, being dominated by Bifidobacterium and Enterobacteriaceae the first and Bacteroides-Prevotella and Clostridium clusters IV and XIVa the second. While in adults TNF-α resulted in a profound impairment of the structure of the enterocyte-associated microbiota fraction, in infants it remained unaffected. Differently from the adult-type gut microbial community, the infant-type microbiota is structured to cope with inflammation, being co-evolved to prime the early immune response by means of transient inflammatory signals from gut microorganisms.
Collapse
Affiliation(s)
- Manuela Centanni
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Silvia Turroni
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Clarissa Consolandi
- Institute of Biomedical Technologies - Italian National Research Council, Milan, Italy
| | - Simone Rampelli
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Clelia Peano
- Institute of Biomedical Technologies - Italian National Research Council, Milan, Italy
| | - Marco Severgnini
- Institute of Biomedical Technologies - Italian National Research Council, Milan, Italy
| | - Elena Biagi
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Giada Caredda
- Institute of Biomedical Technologies - Italian National Research Council, Milan, Italy
| | - Gianluca De Bellis
- Institute of Biomedical Technologies - Italian National Research Council, Milan, Italy
| | - Patrizia Brigidi
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
| | - Marco Candela
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna, Italy
- * E-mail:
| |
Collapse
|
|
27
|
Ng SC, Lam EFC, Lam TTY, Chan Y, Law W, Tse PCH, Kamm MA, Sung JJY, Chan FKL, Wu JCY. Effect of probiotic bacteria on the intestinal microbiota in irritable bowel syndrome. J Gastroenterol Hepatol 2013; 28:1624-31. [PMID: 23800182 DOI: 10.1111/jgh.12306] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/12/2013] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM In irritable bowel syndrome (IBS), the gut microbiota may be altered. Probiotic bacteria appear to be therapeutically effective. We characterized the mucosa-associated microbiota, and determined the clinical and microbiological effects of orally administered probiotic bacteria, in patients with IBS. METHODS Mucosal microbiota from rectal biopsies of IBS patients and controls were assessed on the V1 and V2 variable regions of the 16S ribosomal RNA gene amplified using 454 pyrosequencing. Clinical symptoms and changes in mucosal microbiota were assessed in IBS patients before and after 4 weeks of treatment with probiotic mix VSL#3. RESULTS Ten IBS subjects (eight female; mean age 46 years) were included. At week 4 of probiotic therapy, six patients showed symptom improvement on global symptom assessment compared with baseline (P = 0.031). Before therapy, intestinal microbiota of IBS subjects differed significantly from that of healthy controls, with less diversity and evenness than controls (n = 9; P < 0.05), increased abundance of Bacteroidetes (P = 0.014) and Synegitestes (P = 0.017), and reduced abundance of Actinobacteria (P = 0.004). The classes Flavobacteria (P = 0.028) and Epsilonproteobacteria (P = 0.017) were less enriched in IBS. Abundance differences were largely consistent from the phylum to genus level. Probiotic treatment in IBS patients was associated with a significant reduction of the genus Bacteroides (all taxonomy levels; P < 0.05) to levels similar to that of controls. CONCLUSION In this pilot study, global and deep molecular analysis demonstrates an altered mucosal microbiota composition in IBS. Probiotic leads to detectable changes in the microbiota. These effects of probiotic bacteria may contribute to their therapeutic benefit.
Collapse
Affiliation(s)
- Siew Chien Ng
- Institute of Digestive Disease, Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
28
|
Carroll IM, Ringel-Kulka T, Keku TO, Chang YH, Packey CD, Sartor RB, Ringel Y. Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2011; 301:G799-807. [PMID: 21737778 PMCID: PMC3220325 DOI: 10.1152/ajpgi.00154.2011] [Citation(s) in RCA: 228] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Alterations in the intestinal microbiota have been suggested as an etiological factor in the pathogenesis of irritable bowel syndrome (IBS). This study used a molecular fingerprinting technique to compare the composition and biodiversity of the microbiota within fecal and mucosal niches between patients with diarrhea-predominant IBS (D-IBS) and healthy controls. Terminal-restriction fragment (T-RF) length polymorphism (T-RFLP) fingerprinting of the bacterial 16S rRNA gene was used to perform microbial community composition analyses on fecal and mucosal samples from patients with D-IBS (n = 16) and healthy controls (n = 21). Molecular fingerprinting of the microbiota from fecal and colonic mucosal samples revealed differences in the contribution of T-RFs to the microbiota between D-IBS patients and healthy controls. Further analysis revealed a significantly lower (1.2-fold) biodiversity of microbes within fecal samples from D-IBS patients than healthy controls (P = 0.008). No difference in biodiversity in mucosal samples was detected between D-IBS patients and healthy controls. Multivariate analysis of T-RFLP profiles demonstrated distinct microbial communities between luminal and mucosal niches in all samples. Our findings of compositional differences in the luminal- and mucosal-associated microbiota between D-IBS patients and healthy controls and diminished microbial biodiversity in D-IBS fecal samples further support the hypothesis that alterations in the intestinal microbiota may have an etiological role in the pathogenesis of D-IBS and suggest that luminal and mucosal niches need to be investigated.
Collapse
Affiliation(s)
| | - Tamar Ringel-Kulka
- 2Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
| | | | - Young-Hyo Chang
- 3Korean Collection for Type Cultures, Biological Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
| | - Christopher D. Packey
- 4Department of Microbiology and Immunology, Center for Gastrointestinal Biology and Disease,
| | | | | |
Collapse
|
|
29
|
Enterobacterial microflora in infancy - a case study with enhanced enrichment. Indian J Pediatr 2011; 78:562-8. [PMID: 21249478 DOI: 10.1007/s12098-010-0341-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2009] [Accepted: 11/30/2010] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To validate PMEU (Portable Microbe Enrichment Unit) method for monitoring the composition and development of infantile intestinal enterobacterial microflora. METHODS A case study of a boy with neonatal sepsis is presented. During the first 32 months, he was given 19 systemic antibiotic treatments representing seven different antibiotic classes. Seven fecal samples collected at ages from 3.4 to 31.6 months were studied for enterobacterial strains by a combination of enhanced enrichment culture in the PMEU and plate culture. The identification and phenotypic characterization of the isolates was performed by biochemical tests. RESULTS 37/51 (73%) of the enterobacterial isolates were detected only after the PMEU enrichment. In most samples Escherichia coli strains were predominating, but also several Enterobacter, Klebsiella, Pantoea and Proteus strains could be isolated. It seemed that the antibiotic medications remarkably delayed the development of the intestinal microflora, because first enterobacterial strains were detected only after 6 months of age. CONCLUSIONS The enrichment step turned out to essentially improve the characterization and monitoring of the intestinal enterobacterial microbiota of infants. Compared to plate culture the amount of isolates was 2.6-fold by the PMEU enrichment. This study gives an idea on the development and succession of microbial communities in the gastrointestinal tract and on the variation of the strains due to the intestinal environmental factors.
Collapse
|
|
30
|
Eggesbø M, Moen B, Peddada S, Baird D, Rugtveit J, Midtvedt T, Bushel PR, Sekelja M, Rudi K. Development of gut microbiota in infants not exposed to medical interventions. APMIS 2011; 119:17-35. [PMID: 21143523 PMCID: PMC3058492 DOI: 10.1111/j.1600-0463.2010.02688.x] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Knowledge of the composition of a normal healthy gut microbiota during infancy is important for understanding the role of gut microbiota in disease. A limitation of previous studies is that they are based on infants who have been subject to factors, which can have a profound disruptive effect on the natural colonization process. We describe the colonization process, during the first 4 months after birth, in 85 infants who have experienced no major medical or dietary interventions. They were all vaginally delivered, healthy, term infants, who were not exposed to antibiotics, exclusively breastfed during their first month of life and at least partially breastfed up to 4 months. Selected microbial groups were identified by targeting small subunit microbial ribosomal RNA genes. In contrast to more recent studies, but in agreement with older studies, almost all our infants harbored γ-Proteobacteria and Bifidobacterium. Yet undefined non-cultivable species belonging to Bacteroides, as well as microbes identified as Lachnospiraceae 2, were common. Strong associations were observed between some specific constituents of microbiota at day 4 and the concentration of specific microbial groups at day 120, indicating that early gut microbiota may influence later microbiota. Novel information of the undisturbed composition of early gut microbiota in babies is presented.
Collapse
Affiliation(s)
- Merete Eggesbø
- Department of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
31
|
Durbán A, Abellán JJ, Jiménez-Hernández N, Ponce M, Ponce J, Sala T, D'Auria G, Latorre A, Moya A. Assessing gut microbial diversity from feces and rectal mucosa. MICROBIAL ECOLOGY 2011; 61:123-133. [PMID: 20734040 DOI: 10.1007/s00248-010-9738-y] [Citation(s) in RCA: 121] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2010] [Accepted: 08/05/2010] [Indexed: 02/07/2023]
Abstract
Gut microbiota is the most complex bacterial community in the human body and its study may give important clues to the etiology of different intestinal diseases. Most studies carried out so far have used fecal samples, assuming that these samples have a similar distribution to the communities present throughout the colon. The present study was designed to test this assumption by comparing samples from the rectal mucosa and feces of nine healthy volunteers by sequencing libraries of 16S rRNA genes. At the family taxonomic level, where rarefaction curves indicate that the observed number of taxa is close to the expected one, we observe under different statistical analyses that fecal and mucosal samples cluster separately. The same is found at the level of species considering phylogenetic information. Consequently, it cannot be stated that both samples from a given individual are of similar composition. We believe that the evidence in support of this statement is strong and that it would not change by increasing the number of individuals and/or performing massive sequencing. We do not expect clinicians to stop using feces for research, but we think it is important to caution them on their potential lack of representativeness with respect to the bacterial biofilm on the rectal mucosa.
Collapse
Affiliation(s)
- Ana Durbán
- Centro Superior de Investigación en Salud Pública (CSISP), Avenida de Cataluña 21, 46020, Valencia, Spain
| | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Pesola J, Vaarala O, Heitto A, Hakalehto E. Use of portable enrichment unit in rapid characterization of infantile intestinal enterobacterial microbiota. MICROBIAL ECOLOGY IN HEALTH AND DISEASE 2009. [DOI: 10.3109/08910600903367810] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Jouni Pesola
- Institute of Clinical Medicine, Pediatrics, University of Kuopio, Kuopio
- Department of Pediatrics, Kuopio University Hospital, Kuopio
| | - Outi Vaarala
- National Institute for Health and Welfare, Helsinki
| | - Anneli Heitto
- Department of Biosciences, University of Kuopio, Kuopio
| | - Elias Hakalehto
- Department of Biosciences, University of Kuopio, Kuopio
- Finnoflag Oy, Kuopio and Siilinjärvi, Finland
| |
Collapse
|
|
33
|
Tursi A, Papagrigoriadis S. Review article: the current and evolving treatment of colonic diverticular disease. Aliment Pharmacol Ther 2009; 30:532-46. [PMID: 19549266 DOI: 10.1111/j.1365-2036.2009.04072.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis and consequently diverticular disease. Diverticular disease can be associated with numerous debilitating abdominal and gastrointestinal symptoms (including pain, bloating, nausea, constipation and diarrhoea). AIMS To review the state of treatment for diverticular disease and its complications, and briefly discuss potential future therapies. METHODS PubMed and recent conference abstracts were searched for articles describing the treatment of diverticular disease. RESULTS Many physicians will recommend alterations to lifestyle and increasing fibre consumption. Empirical antibiotics remain the mainstay of therapy for patients with diverticular disease and rifaximin seems to be the best choice. In severe or relapsing disease, surgical intervention is often the only remaining treatment option. Although novel treatment options are yet to become available, the addition of therapies based on mesalazine (mesalamine) and probiotics may enhance treatment efficacy. CONCLUSIONS Data suggest that diverticular disease may share many of the hallmarks of other, better-characterized inflammatory bowel diseases; however, treatment options for patients with diverticular disease are scarce, revolving around antibiotic treatment and surgery. There is a need for a better understanding of the fundamental mechanisms of diverticular disease to design treatment regimens accordingly.
Collapse
Affiliation(s)
- A Tursi
- Digestive Endoscopy Unit, Lorenzo Bonomo Hospital, Andria, Italy.
| | | |
Collapse
|
|
34
|
Shen DH, Shi CR, Chen JJ, Yu SY, Wu Y, Yan WB. Detection of intestinal bifidobacteria and lactobacilli in patients with Hirschsprung's disease associated enterocolitis. World J Pediatr 2009; 5:201-5. [PMID: 19693464 DOI: 10.1007/s12519-009-0038-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2007] [Accepted: 11/11/2008] [Indexed: 01/13/2023]
Abstract
BACKGROUND The etiology of Hirschsprung's disease associated enterocolitis (HAEC) is unknown. Previous investigations have suggested that several factors such as dilation of proximal bowel, changes in colonic mucosal defence, and overgrowth of toxigenic bacteria may be related with it. This study was to quantify bifidobacteria and lactobacilli in the feces of Hirschsprung's disease (HD) patients with or without enterocolitis and those of normal children. METHODS Fresh stool specimens were collected at the first three days of the admission from 30 HD patients (aged 2 weeks to 2 years) and 15 healthy age-matched non-HD patients in the morning once a day for at least three days. All of them have not been given probiotics or antibiotics at least 7 days before stool collection. Hematoxylin-eosin and acetylcholinesterase histochemical staining on rectal biopsies of patients with HD confirmed the diagnosis of HD in all 30 patients. The 30 HD patients were divided into two groups based on the clinical history of enterocolitis: the HAEC group (n=10) and HD group (n=20). Fecal bifidobacteria and lactobacilli were consecutively quantified by SYBR Green I-based real-time PCR assay. Data were analyzed using SAS v. 12.6 for Windows. All tests were two-tailed, and P values <0.05 were considered statistically significant. RESULTS The mean levels of bifidobacteria were 7.35+/-0.59, 8.16+/-1.17, and 8.35+/-0.74 in the HAEC, HD and control groups, respectively. The bifidobacteria colonization levels were lower in the HAEC group than in the HD and control groups (P<0.05, P<0.001 respectively). The mean level of lactobacilli in the HAEC (5.51+/-0.65) and HD groups (5.87+/-0.78) was significantly lower than that in the control group (6.39+/-0.56) (P<0.05). But there was no difference in log numbers of lactobacilli between HAEC and HD groups (P>0.05). CONCLUSIONS The scarcity of bifidobacteria and lactobacilli in HAEC patients may result in a decrease in epithelial barrier function and be a predisposing factor in the development of HAEC. This decline suggests that treatment with probiotics or prebiotics may be beneficial in these individuals. Further research will focus on whether probiotics can decrease the incidence of HAEC.
Collapse
Affiliation(s)
- Di-Hua Shen
- Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai JiaoTong University, 1665 Kongjiang Road, Shanghai, 200092, China
| | | | | | | | | | | |
Collapse
|
|
35
|
Collado MC, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Imbalances in faecal and duodenal Bifidobacterium species composition in active and non-active coeliac disease. BMC Microbiol 2008; 8:232. [PMID: 19102766 PMCID: PMC2635381 DOI: 10.1186/1471-2180-8-232] [Citation(s) in RCA: 150] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2008] [Accepted: 12/22/2008] [Indexed: 12/14/2022] Open
Abstract
Background Gut bifidobacteria are believed to influence immune-related diseases. The objective of this study was to assess the possible relationships between the gut bifidobacteria composition and coeliac disease (CD) in children. A total of 48 faecal samples (30 and 18 samples from active and no active CD patients, respectively) and 33 duodenal biopsy specimens of CD patients (25 and 8 samples from active and non-active CD patients, respectively) were analysed. Samples (30 faecal samples and 8 biopsies) from a control age-matched group of children were also included for comparative purposes. Gut Bifidobacterium genus and species were analyzed by real-time PCR. Results Active and non-active CD patients showed lower numbers of total Bifidobacterium and B. longum species in faeces and duodenal biopsies than controls, and these differences were particularly remarkable between active CD patients and controls. B. catenulatum prevalence was higher in biopsies of controls than in those of active and non-active CD patients, whereas B. dentium prevalence was higher in faeces of non-active CD patients than in controls. Correlations between levels of Bifidobacterium and B. longum species in faecal and biopsy samples were detected in both CD patients and controls. Conclusion Reductions in total Bifidobacterium and B. longum populations were associated with both active and non-active CD when compared to controls. These bacterial groups could constitute novel targets for adjuvant dietary therapies although the confirmation of this hypothesis would require further investigations.
Collapse
Affiliation(s)
- Maria Carmen Collado
- Microbial Ecophysiology and Nutrition Group Institute of Agrochemistry and Food Technology, Spanish National Research Council (CSIC), Burjassot, Valencia, Spain.
| | | | | | | | | |
Collapse
|
|
36
|
Hengst C, Ptok S, Roessler A, Fechner A, Jahreis G. Effects of polydextrose supplementation on different faecal parameters in healthy volunteers. Int J Food Sci Nutr 2008; 60 Suppl 5:96-105. [PMID: 19107626 DOI: 10.1080/09637480802526760] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The beneficial effects of prebiotics on bowel health were thoroughly investigated. The aim of the study was to show prebiotic effects of polydextrose (PDX). A placebo-controlled, randomized intervention study with PDX supplementation (8 g/day) was conducted in 45 healthy subjects. The effects of PDX on stool weight, orofaecal transit time, consistency of stool (Bristol stool form scale), short-chain fatty acid production, pH value, neutral sterol and bile acid excretion and faecal microbiota were evaluated. It was found that supplementation of PDX shortened the orofaecal transit time significantly. Furthermore, ingestion of PDX resulted in a decreased pH value and in significant changes in bile acid and neutral sterol excretion. PDX had no effects on stool weight, concentrations of the main short-chain fatty acids (acetate, propionate) and faecal contents of lactic acid bacteria and bifidobacteria. In conclusion, PDX is able to shorten the orofaecal transit time and to improve stool consistency in subjects suffering from constipation. [corrected]
Collapse
Affiliation(s)
- Christin Hengst
- Department of Nutritional Physiology, Institute of Nutrition, Friedrich Schiller University, Dornburger Strasse 24, Jena, Germany
| | | | | | | | | |
Collapse
|
|
37
|
Probiotics: use in allergic disorders: a Nutrition, Allergy, Mucosal Immunology, and Intestinal Microbiota (NAMI) Research Group Report. J Clin Gastroenterol 2008; 42 Suppl 2:S91-6. [PMID: 18542035 DOI: 10.1097/mcg.0b013e3181639a98] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
The underlying denominators and treatment targets in allergic disorders may be outlined as aberrant barrier functions of the skin epithelium and gut mucosa and dysregulation of the immune response to ubiquitous environmental antigens. Dietary methods to control symptoms and reduce the risk of allergic disease have hitherto focused on elimination diets, alone or in combination with other environmental measures. The results have not been satisfactory regarding long-term prevention, and new approaches are urgently needed. Realization of this, together with the demonstration that the immunophysiologic regulation in the gut depends on the establishment of the healthy gut microbiota, has led to the introduction of novel modes of therapeutic intervention on the basis of the consumption of monocultures and mixed cultures of beneficial live probiotic microorganisms. The current aims of intervention are to avert deviant microbiota development, strengthen the gut barrier function, and alleviate abnormal immune responsiveness. Specific probiotics, selected from members of the healthy intestinal microbiota most of them belonging to Lactobacillus or Bifidobacterium, aid in degradation/structural modification of enteral antigens, regulation of the secretion of inflammatory mediators, and direction of the development of the immune system during the critical period of life when these functions are immature and inexperienced and the risk of allergic disease is heightened. In humans, documented effects have been reported for alleviation of intestinal inflammation, normalization of gut mucosal dysfunction, and down-regulation of hypersensitivity reactions, thereby preferentially targeting allergic conditions with intestinal involvement. The probiotic performance of strains differs; each probiotic strain is a unique organism itself with specific properties that cannot be extrapolated from other, even closely related, strains. Moreover, it would seem simplistic to assume that a single supplementation would suffice to counter the plethora of allergic disease. First, it needs to be acknowledged that a more profound understanding of the complex nature of allergic disorders is needed, as it is likely that there are distinct etiologic factors and pathogenetic mechanisms underlying the heterogeneous manifestations. Second, host-related factors influence the probiotic effects; the distinction in the antiallergic potential of probiotics can be explained by the age of the host and the habitual diet with other potentially active compounds and their conceivable joint probiotic effects. Therefore, research activities are currently focusing on identification of specific strains with immunomodulatory potential, and on the question how the food matrix and dietary content interact with the most efficacious probiotic strains or specific strain combinations.
Collapse
|
|
38
|
Shadid R, Haarman M, Knol J, Theis W, Beermann C, Rjosk-Dendorfer D, Schendel DJ, Koletzko BV, Krauss-Etschmann S. Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity--a randomized, double-blind, placebo-controlled study. Am J Clin Nutr 2007; 86:1426-37. [PMID: 17991656 DOI: 10.1093/ajcn/86.5.1426] [Citation(s) in RCA: 86] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Galactooligosaccharides (GOS) and long-chain fructooligosaccharides (lcFOS) proliferate bifidobacteria in infant gut microbiota. However, it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring. OBJECTIVES We aimed to test how supplementation with GOS and lcFOS (GOS/lcFOS) in the last trimester of pregnancy affects maternal and neonatal gut microbiota. Variables of fetal immunity were assessed as a secondary outcome. DESIGN In a randomized, double-blind, placebo-controlled pilot study, 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS (at a ratio of 9:1) or maltodextrin (placebo) from week 25 of gestation until delivery. Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal (days 5, 20, and approximately 182) stool samples. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis. RESULTS The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group (21.0% and 12.4%, respectively; P = 0.026); the proportion of lactobacilli did not differ between the groups. In neonates, bifidobacteria and lactobacilli percentages, diversity and similarity indexes, and fetal immune parameters did not differ significantly between the 2 groups. Mother-neonate similarity indexes of bifidobacteria decreased over time. CONCLUSIONS GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates. The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables.
Collapse
Affiliation(s)
- Rania Shadid
- Pediatric Immune Regulation Clinical Cooperation Group, Ludwig-Maximilians University of Munich, Germany
| | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Grönlund MM, Gueimonde M, Laitinen K, Kociubinski G, Grönroos T, Salminen S, Isolauri E. Maternal breast-milk and intestinal bifidobacteria guide the compositional development of the Bifidobacterium microbiota in infants at risk of allergic disease. Clin Exp Allergy 2007; 37:1764-72. [PMID: 17941914 DOI: 10.1111/j.1365-2222.2007.02849.x] [Citation(s) in RCA: 189] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The sources and the impact of maternal bacteria on the initial inoculum of the intestinal microflora of newborn infants remain elusive. OBJECTIVE To assess the association between maternal breast-milk and fecal bifidobacteria and infants' fecal bifidobacteria. METHODS Sixty-one mother-infant pairs were included, special emphasis being placed on the maternal allergic status. Bifidobacteria were analysed by a direct PCR method in fecal samples from mothers at 30-35 weeks of gestation and from infants at 1 month of age and from breast-milk samples 1 month post-partum. RESULTS Fecal Bifidobacterium adolescentis and Bifidobacterium bifidum colonization frequencies and counts among mother-infant pairs correlated significantly (P=0.005 and 0.02 for frequencies, respectively, and P=0.002 and 0.01 for counts, respectively). Only infants of allergic, atopic mothers were colonized with B. adolescentis. Each of the breast-milk samples contained bifidobacteria [median 1.4 x 10(3) bacterial cells/mL; interquartile range (IQR) 48.7-3.8 x 10(3)]. Bifidobacterium longum was the most frequently detected species in breast-milk. Allergic mothers had significantly lower amounts of bifidobacteria in breast-milk compared with non-allergic mothers [median 1.3 x 10(3) bacterial cells/mL (IQR 22.4-3.0 x 10(3)) vs. 5.6 x 10(3) bacterial cells/mL (1.8 x 10(3)-1.8 x 10(4)), respectively, (P=0.004)], and their infants had concurrently lower counts of bifidobacteria in feces [3.9 x 10(8) bacterial cells/g (IQR 6.5 x 10(6)-1.5 x 10(9)) in infants of allergic mothers, vs. 2.5 x 10(9) bacterial cells/g (6.5 x 10(8)-3.2 x 10(10)) in infants of non-allergic mothers, P=0.013]. CONCLUSIONS Breast-milk contains significant numbers of bifidobacteria and the maternal allergic status further deranges the counts of bifidobacteria in breast-milk. Maternal fecal and breast-milk bifidobacterial counts impacted on the infants' fecal Bifidobacterium levels. Breast-milk bacteria should thus be considered an important source of bacteria in the establishment of infantile intestinal microbiota.
Collapse
Affiliation(s)
- M-M Grönlund
- Department of Pediatrics, Turku University Central Hospital, Turku, Finland.
| | | | | | | | | | | | | |
Collapse
|
|
40
|
Gueimonde M, Ouwehand A, Huhtinen H, Salminen E, Salminen S. Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease. World J Gastroenterol 2007; 13:3985-9. [PMID: 17663515 PMCID: PMC4171173 DOI: 10.3748/wjg.v13.i29.3985] [Citation(s) in RCA: 85] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To characterize the bifidobacterial microbiota of the colonic mucosa in patients with colon cancer, inflammatory bowel disease or diverticulitis.
METHODS: A sample of the distal colonic mucosa was taken during surgery from a total of 34 patients, twenty-one with diagnosed colorectal cancer, nine with diverticulitis and four with inflammatory bowel disease, requiring surgery for their condition. Bacterial DNA was extracted from the resected mucosal samples and bifidobacterial mucosa-associated microbiota was qualitatively and quantitatively determined by means of qualitative and quantitative PCR.
RESULTS: Bifidobacteria were found in 100% of the samples from patients with diverticulitis or IBD and a 76% of those suffering colon cancer. The species B. longum and B. bifidum were the most widely found, followed by B. animalis, B. catenulatum and B. adolescentis. B. breve, B. dentium and B. angulatum were not detected in any sample. A significantly higher occurrence of B. longum was observed in patients with diverticulitis than in those with colon cancer or IBD (100%, 62% and 75%, respectively, P < 0.05). Similar results were obtained for B. animalis (56%, 0% and 25%, P < 0.05), while B. adolescentis was only found in the mucosa from patients with colon cancer (5 out of 21, 24%). At the quantitative level, patients with colon cancer or IBD showed lower counts of total Bifidobacterium (4.94 and 5.91 vs 6.96 log Cells/sample, respectively, P < 0.05) and of the species B. longum (4.05 and 4.79 vs 6.76, P < 0.05) than those with diverticulitis.
CONCLUSION: Aberrancies in mucosa associated microbiota are present in different intestinal diseases. This may indicate a role of the microbiota in the pathogenesis of these diseases.
Collapse
Affiliation(s)
- Miguel Gueimonde
- Instituto de Productos Lacteos de Asturias (IPLA-CSIC). Ctra. Infiesto s/n, 33300, Villaviciosa, Asturias, Spain.
| | | | | | | | | |
Collapse
|
|
41
|
Chen J, Cai W, Feng Y. Development of intestinal bifidobacteria and lactobacilli in breast-fed neonates. Clin Nutr 2007; 26:559-66. [PMID: 17507117 DOI: 10.1016/j.clnu.2007.03.003] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2006] [Revised: 02/22/2007] [Accepted: 03/22/2007] [Indexed: 11/26/2022]
Abstract
BACKGROUND & AIMS Neonates are subject to numerous factors that affect normal intestinal colonization. This study was to quantify bifidobacteria and lactobacilli in the faeces of breast-fed neonates using quantitative real-time PCR assay, and to investigate the effects of different delivery on the development of bifidobacteria or lactobacilli. METHODS The faecal bifidobacteria and lactobacilli of 40 healthy breast-fed neonates were studied prospectively. Twenty infants were vaginally delivered (VD), and 20 by caesarean delivery (CD) with prophylactically 4 g intravenous cefradine administered to their mothers three times. The faecal bifidobacteria and lactobacilli of neonates were consecutively quantified by SYBR Green I-based real-time PCR assay in the first 7 days after birth. RESULTS The mean levels of bifidobacteria increased from 5.1 to 9.3 in the VD group vs from less than 4.6 to 8.7 in the CD group. The bifidobacteria colonization levels in six samples in the CD group were lower than the limit of detection on day 2. The mean levels of bifidobacteria in the VD group were significantly higher than in the CD group (p<0.05). The mean levels of lactobacilli increased from 4.9 to 7.2 in the VD group vs from 4.9 to 6.9 in the CD group. There was no statistical difference between two groups during the first week (p>0.05). The development of bifidobacteria and lactobacilli showed significant interindividual differences in all infants studied. CONCLUSIONS Primary intestinal bifidobacteria in neonates by caesarean may be disturbed more significantly than lactobacilli.
Collapse
Affiliation(s)
- Jinjin Chen
- Clinical Nutrition Center, Xin Hua Hospital, School of Medicine, Shanghai Jiaotong University, 1665 Kongjiang Road, Shanghai 200092, China.
| | | | | |
Collapse
|
|
42
|
Klein A, Friedrich U, Vogelsang H, Jahreis G. Lactobacillus acidophilus 74-2 and Bifidobacterium animalis subsp lactis DGCC 420 modulate unspecific cellular immune response in healthy adults. Eur J Clin Nutr 2007; 62:584-93. [PMID: 17440520 DOI: 10.1038/sj.ejcn.1602761] [Citation(s) in RCA: 88] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
OBJECTIVE It was determined whether a combination of Lactobacillus acidophilus (L. acidophilus) 74-2 and Bifidobacterium animalis subsp lactis DGCC 420 (B. lactis 420) affect the faecal microbiota as well as immunological parameters and blood lipids in healthy adults. DESIGN A placebo-controlled, double-blinded, randomized crossover trial was conducted. SUBJECTS Twenty-six healthy volunteers (mean age 25 years) were recruited by advertising in academical buildings. All of them completed the study. METHODS After 3-week run-in period, half of the volunteers consumed 300 g/day of yoghurt supplement containing probiotic strains L. acidophilus 74-2 and B. lactis 420, and the other half received the placebo product for a period of 5 weeks. The two groups were crossed during the following 5-week period. Blood and faecal samples were collected at the end of each period. The faecal content of probiotic bacteria, faecal short-chain fatty acids (SCFA), serum lipids and plasma immune system biomarkers were evaluated. RESULTS Faecal proportions of L. acidophilus and of B. lactis increased significantly from 0.02 to 0.19 and 0.4 to 1.4% (P<0.05), respectively. Percentages of granulocytes and monocytes showing phagocytic activity were significantly elevated from 92 to 95% during probiotic intervention, whereas their oxidative burst activity and specific immune parameters remained unaffected. Fecal SCFA and serum cholesterol levels were not influenced by the probiotics. However, serum concentrations of triacylglyceroles decreased significantly by 11.6% (P<0.05) in the probiotic supplementation period. CONCLUSIONS L. acidophilus and B. lactis were recovered in faeces in significantly elevated numbers after supplementation. They are able to modulate unspecific cellular immune response indicated by the increased phagocytic activity.
Collapse
Affiliation(s)
- A Klein
- Institute of Nutrition, Department of Nutritional Physiology, Friedrich Schiller University, Dornburger Strasse 24, Jena, Germany
| | | | | | | |
Collapse
|
|
43
|
Rinne M, Kalliomäki M, Salminen S, Isolauri E. Probiotic intervention in the first months of life: short-term effects on gastrointestinal symptoms and long-term effects on gut microbiota. J Pediatr Gastroenterol Nutr 2006; 43:200-5. [PMID: 16877985 DOI: 10.1097/01.mpg.0000228106.91240.5b] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To determine whether probiotics administered for 6 months postnatally affect gastrointestinal symptoms, crying and the compositional development of the gut microbiota through infancy. METHODS The study comprised of 132 newborns whose mothers were randomized to receive placebo or Lactobacillus rhamnosus GG (ATCC 53103) before delivery. The treatments of mothers/infants continued for 6 months postnatally. A specific symptom chart was used to monitor gastrointestinal symptoms and infant's crying during the 7th and the 12th weeks of life. Fluorescent in situ hybridization was used to establish the Bifidobacterium, Lactobacillus/Enterococcus, Bacteroides and Clostridium counts in fecal samples at 6, 12, 18 and 24 months of age. RESULTS Numbers of different types of stools, vomits and crying time were comparable between the groups during the 7th and the 12th weeks of life. Dominant microbiota consisted of bifidobacteria throughout the study. At 6 months, there were less clostridia in faeces in the placebo compared with the probiotic group (P = 0.026), whereas after long-term follow-up at 2 years, there were less lactobacilli/enterococci and clostridia in faeces in the probiotic group than in the placebo group (P = 0.011 and P = 0.032, respectively), reflecting the impact of clostridia as a marker of microbiota succession in healthy infants. CONCLUSIONS Probiotic administration in the first months of life was well tolerated and did not significantly interfere with long-term composition or quantity of gut microbiota.
Collapse
Affiliation(s)
- Minna Rinne
- Department of Pediatrics, Turku University Central Hospital, Finland.
| | | | | | | |
Collapse
|
|
44
|
Fallani M, Rigottier-Gois L, Aguilera M, Bridonneau C, Collignon A, Edwards CA, Corthier G, Doré J. Clostridium difficile and Clostridium perfringens species detected in infant faecal microbiota using 16S rRNA targeted probes. J Microbiol Methods 2006; 67:150-61. [PMID: 16647148 DOI: 10.1016/j.mimet.2006.03.010] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2005] [Revised: 02/16/2006] [Accepted: 03/09/2006] [Indexed: 11/19/2022]
Abstract
Clostridium perfringens and Clostridium difficile are pathogenic clostridia potentially associated with gastrointestinal infections and allergy in infants. To enable the molecular detection and quantification of these species in the infant gut, two 16S rRNA oligonucleotide probes were developed: Cdif198 for C. difficile and Cperf191 for C. perfringens. We defined the probes in silico using the RDP sequence database. The probes were then validated using FISH combined with flow cytometry and a collection of target and non-target strains, and faecal samples inoculated with dilutions of C. difficile and C. perfringens strains. These new probes were used to assess the composition of the intestinal microbiota of 33 infants of 1.5 to 18.5 months of age, associated with a panel of 8 probes targeting the predominant faecal bacterial groups of humans. The probes designed allowed detection and quantification of the relative proportions of C. difficile (0.5+/-1.0%) and C. perfringens (2.1+/-2.3%) in the microbiota of infants.
Collapse
Affiliation(s)
- Matteo Fallani
- Institut National de la Recherche Agronomique, Unité d'Ecologie et de Physiologie du Système Digestif, Jouy en Josas, France
| | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Amrouche T, Boutin Y, Moroni O, Kheadr E, Fliss I. Production and characterization of anti-bifidobacteria monoclonal antibodies and their application in the development of an immuno-culture detection method. J Microbiol Methods 2006; 65:159-70. [PMID: 16182395 DOI: 10.1016/j.mimet.2005.07.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2005] [Revised: 06/07/2005] [Accepted: 07/05/2005] [Indexed: 11/17/2022]
Abstract
An immuno-culture method has been developed by combination of specific monoclonal antibodies and plate culture to allow detection of viable bifidobacteria. Cell wall proteins were selected as surface antigen to produce antibodies against bifidobacteria. The cell wall proteins were extracted and purified from six ATCC strains of bifidobacteria grown in MRS broth using an anaerobic system. To compare the profile of the protein extracts, all the protein solutions obtained were analyzed by SDS-PAGE. Similar bands corresponding to the major proteins of each species of bifidobacteria were observed. The proteins were tested for their immunogenicity in Balb/c mice after immunization and subsequent analysis using ELISA procedures. High immune responses were generated in mice immunized by proteins from Bifidobacterium bifidum and Bifidobacterium longum. Monoclonal antibodies were produced against B. longum and tested for their specificity, sensitivity and cross reactivity with other bifidobacteria species. All the hybridoma cells selected produced anti-B. longum antibodies cross-reacting with native and purified proteins from five other bifidobacteria species. An epitope supported by a cross-reacting protein of 58 kDa shared by bifidobacteria was revealed by western blot. This was confirmed by immune-transmission electron microscopy observations which showed the specific interaction of these antibodies with bifidobacterial cell wall proteins. Also, the antibody obtained was found to be specific for the genus Bifidobacterium and sensitive, allowing the detection of at least 10(5) target cells/ml. An immuno-culture detection approach was then developed using the selected anti-B. longum antibodies. This method was shown to be very efficient for the detection of viable cells of bifidobacteria suggesting the possibility of its use to quantify these bacteria in various food matrices.
Collapse
Affiliation(s)
- T Amrouche
- Dairy Research Center STELA, Pavillon Paul-Comtois, Université Laval, Québec (Qc), Canada G1K 7P4
| | | | | | | | | |
Collapse
|