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Leo S, Leonard MM, Valitutti F, Fasano A. Gut dysbiosis: cause or consequence of intestinal inflammation in celiac disease? Expert Rev Gastroenterol Hepatol 2025:1-9. [PMID: 40133841 DOI: 10.1080/17474124.2025.2483406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 03/19/2025] [Indexed: 03/27/2025]
Abstract
INTRODUCTION Celiac disease (CeD) is an immune-mediated condition that occurs in genetically predisposed individuals ingesting gluten. It is characterized by enteropathy leading to both gastrointestinal and extra-intestinal symptoms. The prevalence of CeD has increased world-wide. Evidence suggests that genetic predisposition and exposure to gluten are necessary but not sufficient for CeD onset, implying that other unknown factors are at play in its pathogenesis. AREAS COVERED This review summarizes the current knowledge on the contribution of the gut microbiota to CeD pathogenesis, aiming to address the question of whether it is the cause or consequence of the celiac enteropathy. We reviewed the current literature (studies published in PubMed database between 2007 and 2023), linking gut microbiota dysbiosis and CeD, focusing specifically on prospective birth cohorts' studies and discussing how multi-omics and artificial intelligence (AI) could transform the diagnosis of CeD in a personalized medicine approach. EXPERT OPINION A multi-omic approach will allow for better clarification of the pivotal role of the microbiome in epigenetically triggering CeD pathogenesis. Further, the combination of multi-omics results with AI would pave the way to an improved CeD diagnosis and to the identification of new personalized therapeutic interventions.
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Affiliation(s)
- Stefano Leo
- European Biomedical Research Institute of Salerno, Salerno, Italy
| | - Maureen M Leonard
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA
- Celiac Research Program, Harvard Medical School, Boston, MA, USA
| | - Francesco Valitutti
- Pediatrics Section, Department of Medicine and Surgery, University of Perugia, Perugia, Italy
| | - Alessio Fasano
- European Biomedical Research Institute of Salerno, Salerno, Italy
- Division of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA
- Mucosal Immunology and Biology Research Center, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA, USA
- Celiac Research Program, Harvard Medical School, Boston, MA, USA
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Kelley K, Dogru D, Huang Q, Yang Y, Palm NW, Altindis E, Ludvigsson J. Children who develop celiac disease are predicted to exhibit distinct metabolic pathways among their gut microbiota years before diagnosis. Microbiol Spectr 2025; 13:e0146824. [PMID: 39902908 DOI: 10.1128/spectrum.01468-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 01/07/2025] [Indexed: 02/06/2025] Open
Abstract
Celiac disease (CD) is an autoimmune disease caused by a loss of gluten tolerance in genetically predisposed individuals. While 30%-40% of people possess the predisposing alleles, only 1%-2% are diagnosed with CD, suggesting that environmental factors are involved in disease pathogenesis. To determine an association between pediatric CD and the gut microbiome, we analyzed fecal samples from a prospective cohort study (ABIS). These samples were collected from children who later developed CD (CD progressors) and age-matched healthy children (at ages 1, 2.5, and 5) with similar HLA genotypes, breastfeeding durations, and gluten exposure times. We previously reported gut microbiome differences at ages 2.5 and 5 in this cohort; here, we present findings from samples collected at age 1 (n = 5). We identified 14 ASVs differing significantly between CD progressors and controls, including taxa linked to CD pathogenesis. CD progressors had increased Firmicutes and higher alpha diversity in IgA- bacteria. Using PICRUSt, we analyzed metabolic pathways enriched in CD progressors compared to controls at ages 1, 2.5, and 5 (n = 5-16), revealing enriched inflammatory and pathogenic pathways potentially contributing to CD-related immune dysregulation. While results are based on the primary EdgeR analysis, we also applied a non-parametric method of statistical analysis, reporting those results with supplementary figures. In conclusion, our findings suggest distinct metabolic pathways enriched in the gut microbiome of CD progressors years before diagnosis, which could inform targeted therapeutics for CD. As discussed in the limitations section, this small pilot study should be replicated with larger sample sizes for broader generalization. IMPORTANCE We analyzed gut microbiome data from children who later developed celiac disease (CD progressors) compared to healthy children in the first 5 years of life. Using fecal samples corresponding to the three phases of gut microbiome development, we uncovered enriched functional microbial pathways in CD progressors at age 1. Some of these pathways, implicated in bacterial pathogenesis, microbiota modulation, and inflammation, have been correlated with CD. We also identified taxa in CD progressors at age 1 including Lachnospiraceae, Alistipes, and Bifidobacterium dentium that were previously associated with CD. These findings suggest a potential role for these taxa and enriched pathways in pediatric CD onset years before diagnosis, highlighting potential for early interventions. While the findings of this exploratory study should be validated with larger sample sizes, our study suggests microbial metabolic pathways related to CD onset, enhancing our understanding of CD pathogenesis and the role of gut microbiome-mediated early alterations.
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Affiliation(s)
- Kristina Kelley
- Boston College Biology Department, Chestnut Hill, Massachusetts, USA
| | - Dogus Dogru
- Boston College Biology Department, Chestnut Hill, Massachusetts, USA
| | - Qian Huang
- Boston College Biology Department, Chestnut Hill, Massachusetts, USA
| | - Yi Yang
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Noah W Palm
- Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Emrah Altindis
- Boston College Biology Department, Chestnut Hill, Massachusetts, USA
| | - Johnny Ludvigsson
- Crown Princess Victoria's Children's Hospital, Region Östergötland, Linköping, Sweden
- Division of Pediatrics, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
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Catassi G, Lener E, Grattagliano MM, Motuz S, Zavarella MA, Bibbò S, Cammarota G, Gasbarrini A, Ianiro G, Catassi C. The role of microbiome in the development of gluten-related disorders. Best Pract Res Clin Gastroenterol 2024; 72:101951. [PMID: 39645285 DOI: 10.1016/j.bpg.2024.101951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 08/07/2024] [Accepted: 09/03/2024] [Indexed: 12/09/2024]
Abstract
Gluten-related disorders (GRD) include celiac disease (CD), non celiac gluten sensitivity (NCGS) and wheat allergy (WA), conditions that are associated with the ingestion of gluten-containing food. Gut microbiota composition and function may be involved in the pathogenesis of GRD. In untreated CD the microbiota is characterized by a reduction in beneficial microbes like Lactobacillus and Bifidobacterium and an increase in pathogenic ones such as Bacteroides and E. coli. Dysbiosis is a hallmark of CD, persists across various disease stages and is only partially corrected by a gluten-free diet. NCGS patients show a different microbial profile, with a notable decrease in microbial richness, and an increase of Ruminococcaceae and decrease of Bacteroidetes and Fusobacteria. The increase of certain bacterial groups such as Clostridium and Anaerobacter, in contrast with the decline of Bacteroides and Clostridium XVIII, marks a distinctive microbial signature associated with allergic responses to food. Mechanisms linking the gut microbiota to the development of GRD include effects on the gut barrier function, microbiota-mediated immune response to gluten, and an impact of microbial metabolites on gluten digestion and tolerance. Although the gluten-free diet is the primary therapy of GRDs, treatment with probiotics may contribute to improve the natural history of these disorders, for instance by minimizing the damaging effects of gluten contamination and accelerating the catch-up growth at the beginning of the dietary treatment of CD. Additional high-quality trials are still needed to identify and standardize the use of probiotics/prebiotics in GRDs.
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Affiliation(s)
- Giulia Catassi
- Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy; Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome - Umberto I Hospital, Rome, Italy
| | - Elena Lener
- Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie Dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Maria Maddalena Grattagliano
- Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie Dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Sofya Motuz
- Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie Dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Maria Antonietta Zavarella
- Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie Dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Stefano Bibbò
- Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie Dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie Dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie Dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica Del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie Dell'Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy
| | - Carlo Catassi
- Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, USA.
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Galipeau HJ, Hinterleitner R, Leonard MM, Caminero A. Non-Host Factors Influencing Onset and Severity of Celiac Disease. Gastroenterology 2024; 167:34-50. [PMID: 38286392 PMCID: PMC11653303 DOI: 10.1053/j.gastro.2024.01.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 01/19/2024] [Accepted: 01/22/2024] [Indexed: 01/31/2024]
Abstract
Celiac disease (CeD) is a chronic autoimmune condition driven by gluten ingestion in genetically predisposed individuals, resulting in inflammatory lesions in the proximal small intestine. Although the presence of specific HLA-linked haplotypes and gluten consumption are necessary for disease development, they alone do not account for the variable onset of CeD in susceptible individuals. This review explores the multifaceted role of non-host factors in CeD development, including dietary and microbial influences. We discuss clinical associations and observations highlighting the impact of these factors on disease onset and severity. Furthermore, we discuss studies in CeD-relevant animal models that offer mechanistic insights into how diet, the microbiome, and enteric infections modulate CeD pathogenesis. Finally, we address the clinical implications and therapeutic potential of understanding these cofactors offering a promising avenue for preventive and therapeutic interventions in CeD management.
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Affiliation(s)
- Heather J Galipeau
- Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
| | - Reinhard Hinterleitner
- Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Maureen M Leonard
- Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, Massachusetts; Center for Celiac Research and Treatment, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Alberto Caminero
- Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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Annunziato A, Vacca M, Cristofori F, Dargenio VN, Celano G, Francavilla R, De Angelis M. Celiac Disease: The Importance of Studying the Duodenal Mucosa-Associated Microbiota. Nutrients 2024; 16:1649. [PMID: 38892582 PMCID: PMC11174386 DOI: 10.3390/nu16111649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 05/24/2024] [Accepted: 05/24/2024] [Indexed: 06/21/2024] Open
Abstract
There is increasing evidence indicating that changes in both the composition and functionality of the intestinal microbiome are closely associated with the development of several chronic inflammatory diseases, with celiac disease (CeD) being particularly noteworthy. Thanks to the advent of culture-independent methodologies, the ability to identify and quantify the diverse microbial communities residing within the human body has been significantly improved. However, in the context of CeD, a notable challenge lies in characterizing the specific microbiota present on the mucosal surfaces of the intestine, rather than relying solely on fecal samples, which may not fully represent the relevant microbial populations. Currently, our comprehension of the composition and functional importance of mucosa-associated microbiota (MAM) in CeD remains an ongoing field of research because the limited number of available studies have reported few and sometimes contradictory results. MAM plays a crucial role in the development and progression of CeD, potentially acting as both a trigger and modulator of the immune response within the intestinal mucosa, given its proximity to the epithelial cells and direct interaction. According to this background, this review aims to consolidate the existing literature specifically focused on MAM in CeD. By elucidating the complex interplay between the host immune system and the gut microbiota, we aim to pave the way for new interventions based on novel therapeutic targets and diagnostic biomarkers for MAM in CeD.
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Affiliation(s)
- Alessandro Annunziato
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (A.A.); (G.C.); (M.D.A.)
| | - Mirco Vacca
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (A.A.); (G.C.); (M.D.A.)
| | - Fernanda Cristofori
- Interdisciplinary Department of Medicine, Pediatric Section, Children’s Hospital ‘Giovanni XXIII’, University of Bari Aldo Moro, 70126 Bari, Italy; (F.C.); (V.N.D.); (R.F.)
| | - Vanessa Nadia Dargenio
- Interdisciplinary Department of Medicine, Pediatric Section, Children’s Hospital ‘Giovanni XXIII’, University of Bari Aldo Moro, 70126 Bari, Italy; (F.C.); (V.N.D.); (R.F.)
| | - Giuseppe Celano
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (A.A.); (G.C.); (M.D.A.)
| | - Ruggiero Francavilla
- Interdisciplinary Department of Medicine, Pediatric Section, Children’s Hospital ‘Giovanni XXIII’, University of Bari Aldo Moro, 70126 Bari, Italy; (F.C.); (V.N.D.); (R.F.)
| | - Maria De Angelis
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (A.A.); (G.C.); (M.D.A.)
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Aydin A, Suleymanoglu AA, Abdramanov A, Paulsen P, Dumen E. Detection of Extended Spectrum ß-Lactamase-Producing Escherichia coli with Biofilm Formation from Chicken Meat in Istanbul. Foods 2024; 13:1122. [PMID: 38611426 PMCID: PMC11011584 DOI: 10.3390/foods13071122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 03/30/2024] [Accepted: 04/04/2024] [Indexed: 04/14/2024] Open
Abstract
Antimicrobial resistance is one of the major public health problems worldwide. This study aimed to detect the presence of extended-spectrum β-lactamase-(ESBL-)producing Escherichia (E.) coli in chicken meat in Istanbul, Türkiye. Raw chicken meat samples (n = 208) were collected from different sale points and analyzed for ESBL-producing E. coli. In total, 101 (48.5%) isolates were confirmed as E. coli by PCR, of which 80/101 (79.2%) demonstrated multiple antibiotic resistance. Resistance against amoxicillin-clavulanic acid was most frequent (87.1%). Eighteen isolates (17.8%) demonstrated phenotypical ESBL resistance, as assessed by the double disc synergy test (DDST). Isolates were tested for the presence of β-lactamase genes and mobilized colistin-resistant genes. The blaTEM group was most frequently detected (97.02%), followed by blaCTX m (45.5%), blaSHV (9.9%), and blaOXA-2 (0.9%). However, mcr genes and blaNDM,blaKPC, blaVIM, and blaOXA-48 genes were not found in any isolate. E. coli strains were tested for biofilm formation in six different media [Nutrient broth, LB broth, Tryptone Soya broth (TSB), TSB containing 1% sucrose, TSB containing 0.6% yeast extract, and BHI]. Biofilm formation by E. coli isolates (44/101, 43.5%) was highest in TSB with 1% sucrose. It is worth noting that all biofilm-producing isolates were found to harbor the blaTEM-1 gene, which can indicate a high level of antibiotic resistance. This is the first report about ESBL-producing E. coli in poultry meat, the exposure of consumers in Istanbul metropolitan areas, and the ability of E. coli from this region to produce biofilms.
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Affiliation(s)
- Ali Aydin
- Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, İstanbul University-Cerrahpaşa, 34320 Istanbul, Türkiye; (A.A.S.); (E.D.)
| | - Ali Anil Suleymanoglu
- Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, İstanbul University-Cerrahpaşa, 34320 Istanbul, Türkiye; (A.A.S.); (E.D.)
| | - Abzal Abdramanov
- Department of Veterinary Sanitary Examination and Hygiene, Kazakh National Agrarian Research University, 050010 Almaty, Kazakhstan;
| | - Peter Paulsen
- Unit for Food Hygiene and Technology, Centre for Food Science and Veterinary Public Health, Clinical Department for Farm Animals and Food System Science, University of Veterinary Medicine Vienna, 1210 Vienna, Austria
| | - Emek Dumen
- Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, İstanbul University-Cerrahpaşa, 34320 Istanbul, Türkiye; (A.A.S.); (E.D.)
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Lai C, Chen L, Zhong X, Tang Z, Zhang B, Luo Y, Li C, Jin M, Chen X, Li J, Shi Y, Sun Y, Guo L. Long-term effects on liver metabolism induced by ceftriaxone sodium pretreatment. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2023; 335:122238. [PMID: 37506808 DOI: 10.1016/j.envpol.2023.122238] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 07/16/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023]
Abstract
Ceftriaxone is an emerging contaminant due to its potential harm, while its effects on liver are still need to be clarified. In this study, we first pretreated the 8-week-old C57BL/6J mice with high dose ceftriaxone sodium (Cef, 400 mg/mL, 0.2 mL per dose) for 8 days to prepare a gut dysbiosis model, then treated with normal feed for a two-month recovery period, and applied non-targeted metabolomics (including lipidomics) to investigate the variations of fecal and liver metabolome, and coupled with targeted determination of fecal short-chain fatty acids (SCFAs) and bile acids (BAs). Lastly, the correlations and mediation analysis between the liver metabolism and gut metabolism/microbes were carried, and the potential mechanisms of the mal-effects on gut-liver axis induced by Cef pretreatment were accordingly discussed. Compared to the control group, Cef pretreatment reduced the rate of weight gain and hepatosomatic index, induced bile duct epithelial cells proliferated around the central vein and appearance of binucleated hepatocytes, decreased the ratio of total branching chains amino acids (BCAAs) to total aromatic amino acids (AAAs) in liver metabolome. In fecal metabolome, the total fecal SCFAs and BAs did not change significantly while butyric acid decreased and the primary BAs increased after Cef pretreatment. Correlation and mediation analysis revealed one potential mechanism that Cef may first change the intestinal microbiota (such as destroying its normal structure, reducing its abundance and the stability of the microbial network or certain microbe abundance like Alistipes), and then change the intestinal metabolism (such as acetate, caproate, propionate), leading to liver metabolic disorder (such as spermidine, inosine, cinnamaldehyde). This study proved the possibility of Cef-induced liver damage, displayed the overall metabolic profile of the liver following Cef pretreatment and provided a theoretical framework for further research into the mechanism of Cef-induced liver damage.
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Affiliation(s)
- Chengze Lai
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Linkang Chen
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Xiaoting Zhong
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Zeli Tang
- Department of Pathology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China
| | - Bin Zhang
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Yu Luo
- Guangzhou Liwan District Center for Disease Control and Prevention, Guangzhou, Guangdong, China
| | - Chengji Li
- Yunfu Disease Control and Prevention Center, Guang Dong Province, China
| | - Mengcheng Jin
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Xu Chen
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Jinglin Li
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Yinying Shi
- Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China
| | - Yanqin Sun
- Department of Pathology, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China
| | - Lianxian Guo
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, China.
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Jenickova E, Andrén Aronsson C, Mascellani Bergo A, Cinek O, Havlik J, Agardh D. Effects of Lactiplantibacillus plantarum and Lacticaseibacillus paracasei supplementation on the faecal metabolome in children with coeliac disease autoimmunity: a randomised, double-blinded placebo-controlled clinical trial. Front Nutr 2023; 10:1183963. [PMID: 37485388 PMCID: PMC10359497 DOI: 10.3389/fnut.2023.1183963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Accepted: 06/08/2023] [Indexed: 07/25/2023] Open
Abstract
Introduction Coeliac disease is a lifelong immune-mediated enteropathy manifested as gluten intolerance in individuals carrying specific human leukocyte antigen (HLA) molecules. Other factors than genetics and gluten intake, however, may play a role in triggering the disease. The gut internal environment is thought to be one of these potential contributing factors, and it can be influenced throughout life. Methods We examine the impact of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 supplementation on the faecal metabolome in genetically predisposed children having tissue transglutaminase autoantibodies, i.e., coeliac disease autoimmunity. Probiotic strains were selected based on their beneficial properties, including mucosal permeability and immune modulation effects. The intervention group (n = 40) and control group (n = 38) took the probiotics or placebo daily for 6 months in a double-blinded randomised trial. Faecal samples were collected at baseline and after 3 and 6 months and analysed using the 1H NMR for metabolome. The incorporation of 16S rRNA sequencing as a supportive dataset complemented the analysis of the metabolome data. Results During the 6 months of intervention, the stool concentrations of 4-hydroxyphenylacetate increased in the intervention group as compared to controls, whereas concentrations of threonine, valine, leucine, isoleucine, methionine, phenylalanine, aspartate, and fumarate decreased. Additionally, a noteworthy effect on the glycine, serine, and threonine metabolic pathway has been observed. Conclusion The findings suggest a modest yet significant impact of the probiotics on the faecal metabolome, primarily influencing proteolytic processes in the gut. Clinical trial registration ClinicalTrials.gov, NCT03176095.
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Affiliation(s)
- Eliska Jenickova
- Department of Food Science, Czech University of Life Sciences Prague, Prague, Czechia
| | | | - Anna Mascellani Bergo
- Department of Food Science, Czech University of Life Sciences Prague, Prague, Czechia
| | - Ondrej Cinek
- Department of Pediatrics and Department of Medical Microbiology, Charles University in Prague and University Hospital Motol, Prague, Czechia
| | - Jaroslav Havlik
- Department of Food Science, Czech University of Life Sciences Prague, Prague, Czechia
| | - Daniel Agardh
- Department of Clinical Sciences, Lund University, Malmö, Sweden
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González-García BP, Marí S, Cilleros-Portet A, Hernangomez-Laderas A, Fernandez-Jimenez N, García-Santisteban I, Bilbao JR. Two-Sample Mendelian Randomization detects bidirectional causality between gut microbiota and celiac disease in individuals with high genetic risk. Front Immunol 2023; 14:1082862. [PMID: 37457693 PMCID: PMC10347381 DOI: 10.3389/fimmu.2023.1082862] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 06/07/2023] [Indexed: 07/18/2023] Open
Abstract
Background Celiac Disease (CeD) is an autoimmune disorder triggered by gluten intake in genetically susceptible individuals. Highest risk individuals are homozygous for the Human Leucocyte Antigen (HLA) DQ2.5 haplotype or DQ2.5/DQ2.2 heterozygous. Both the HLA-DQ2-positive high genetic risk individuals and those that have developed the disease have altered intestinal microbiota, but it remains unclear whether these alterations are a cause or a consequence of CeD. Objective To investigate a potential bidirectional causality between gut microbiota (GM) and CeD in HLA-DQ2 high genetic risk individuals. Materials and Methods We performed a bidirectional Two-Sample Mendelian Randomization (2SMR) test using summary statistics from the largest publicly available Genome-Wide Association Study (GWAS) of GM and the summary statistics of the Immunochip CeD study of those individuals with the HLA-DQ2 high-risk haplotype. To test whether changes in GM composition were causally linked to CeD, GM data were used as exposure and CeD data as outcome; to test for reverse causation, the exposure and outcome datasets were inverted. Results We identified several bacteria from Ruminococcaceae and Lachnospiraceae families of the Firmicutes phylum as potentially causal in both directions. In addition, our results suggest that changes in the abundance of Veillonellaceae family might be causal in the development of CeD, while alterations in Pasteurellaceae family might be a consequence of the disease itself. Conclusion Our results suggest that the relationship between GM and HLA-DQ2 high risk individuals is highly complex and bidirectional.
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Affiliation(s)
- Bárbara P. González-García
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU) and Biocruces Bizkaia Health Research Institute, Leioa, Spain
| | - Sergi Marí
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU) and Biocruces Bizkaia Health Research Institute, Leioa, Spain
| | - Ariadna Cilleros-Portet
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU) and Biocruces Bizkaia Health Research Institute, Leioa, Spain
| | - Alba Hernangomez-Laderas
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU) and Biocruces Bizkaia Health Research Institute, Leioa, Spain
| | - Nora Fernandez-Jimenez
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU) and Biocruces Bizkaia Health Research Institute, Leioa, Spain
| | - Iraia García-Santisteban
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU) and Biocruces Bizkaia Health Research Institute, Leioa, Spain
| | - Jose Ramon Bilbao
- Department of Genetics, Physical Anthropology and Animal Physiology, University of the Basque Country (UPV/EHU) and Biocruces Bizkaia Health Research Institute, Leioa, Spain
- Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM), Madrid, Spain
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10
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Stefura T, Rusinek J, Zając M, Zapała B, Gosiewski T, Sroka-Oleksiak A, Salamon D, Pędziwiatr M, Major P. Duodenal microbiota and weight-loss following sleeve gastrectomy and Roux-en-Y gastric bypass - a pilot study. BMC Surg 2023; 23:173. [PMID: 37365522 PMCID: PMC10291748 DOI: 10.1186/s12893-023-02076-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 06/13/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Bariatric surgery is the most effective method of morbid obesity treatment. Microbiota has many functions in human body and many of them remain to be unknown. The aim of this study was to establish if the composition of duodenal microbiota influences success rate of bariatric surgery. METHODS It was a prospective cohort study. The data concerning demographics and comorbidities was collected perioperatively. The duodenal biopsies were collected prior to surgery with the gastroscope. Then DNA analysis was conducted. The data connected to the operation outcomes was gathered after 6 and 12 months after surgery. RESULTS Overall, 32 patients were included and divided into two groups (successful - group 1 and unsuccessful - group 0) based on percentage excess weight loss after 6 months were created. The Total Actual Abundance was higher in group 0. In group 0 there was a significantly higher amount of Roseburia and Arthrobacter (p = 0.024, p = 0.027, respectively). Genus LDA effect size analysis showed Prevotella, Megasphaera and Pseudorhodobacter in group 1 to be significant. Whereas abundance of Roseburia and Arthrobacter were significant in group 0. CONCLUSIONS Duodenal microbiota composition may be a prognostic factor for the success of the bariatric surgery but further research on the larger group is needed.
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Affiliation(s)
- Tomasz Stefura
- Department of Medical Education, Jagiellonian University Medical College, Krakow, Poland
| | - Jakub Rusinek
- Students' Scientific Group at 2nd Department of General Surgery, Jagiellonian University, Medical College, Krakow, Poland
| | - Maciej Zając
- Students' Scientific Group at 2nd Department of General Surgery, Jagiellonian University, Medical College, Krakow, Poland
| | - Barbara Zapała
- Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
| | - Tomasz Gosiewski
- Department of Microbiology, Jagiellonian University Medical College, Krakow, Poland
| | | | - Dominika Salamon
- Department of Microbiology, Jagiellonian University Medical College, Krakow, Poland
| | - Michał Pędziwiatr
- 2nd Department of General Surgery, Jagiellonian University Medical College, Kopernika 21 St, 31-501, Kraków, Poland
| | - Piotr Major
- 2nd Department of General Surgery, Jagiellonian University Medical College, Kopernika 21 St, 31-501, Kraków, Poland.
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11
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Manai F, Zanoletti L, Arfini D, Micco SGD, Gjyzeli A, Comincini S, Amadio M. Dimethyl Fumarate and Intestine: From Main Suspect to Potential Ally against Gut Disorders. Int J Mol Sci 2023; 24:9912. [PMID: 37373057 DOI: 10.3390/ijms24129912] [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: 05/20/2023] [Revised: 06/04/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
Dimethyl fumarate (DMF) is a well-characterized molecule that exhibits immuno-modulatory, anti-inflammatory, and antioxidant properties and that is currently approved for the treatment of psoriasis and multiple sclerosis. Due to its Nrf2-dependent and independent mechanisms of action, DMF has a therapeutic potential much broader than expected. In this comprehensive review, we discuss the state-of-the-art and future perspectives regarding the potential repurposing of DMF in the context of chronic inflammatory diseases of the intestine, such as inflammatory bowel disorders (i.e., Crohn's disease and ulcerative colitis) and celiac disease. DMF's mechanisms of action, as well as an exhaustive analysis of the in vitro/in vivo evidence of its beneficial effects on the intestine and the gut microbiota, together with observational studies on multiple sclerosis patients, are here reported. Based on the collected evidence, we highlight the new potential applications of this molecule in the context of inflammatory and immune-mediated intestinal diseases.
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Affiliation(s)
- Federico Manai
- Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy
| | - Lisa Zanoletti
- Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy
- Department of Chronic Diseases and Metabolism (CHROMETA), Katholieke Universiteit Leuven, 3000 Leuven, Belgium
| | - Davide Arfini
- Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy
| | - Simone Giorgio De Micco
- Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy
| | - Arolda Gjyzeli
- Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy
| | - Sergio Comincini
- Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, 27100 Pavia, Italy
| | - Marialaura Amadio
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy
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12
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Yamauchi T, Koyama N, Hirai A, Suganuma H, Suzuki S, Murashita K, Mikami T, Tamada Y, Sato N, Imoto S, Itoh K, Nakaji S. Definition of a Dietary Pattern Expressing the Intake of Vegetables and Fruits and Its Association with Intestinal Microbiota. Nutrients 2023; 15:2104. [PMID: 37432274 DOI: 10.3390/nu15092104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/22/2023] [Accepted: 04/25/2023] [Indexed: 07/12/2023] Open
Abstract
Daily dietary habits directly or indirectly influence the intestinal microbiota, and the resulting changes in its composition and metabolic activity alter the health conditions of the host. Although many studies have analyzed the association between individual nutrients/food items and intestinal microbiota, the assessment of the diet and intestinal microbiota from a macroscopic perspective has not yet been performed in Japan. Therefore, we focused on vegetables and fruits and aimed to identify dietary patterns of high intake of these foods and to examine their relationship with the intestinal microbiota. This cross-sectional study included 1019 healthy individuals aged ≥20 years in a rural area in northern Japan. Six dietary patterns were detected by factor analysis using the brief-type self-administered diet history questionnaire (BDHQ) data to identify the "vege pattern", which was the dietary pattern rich in vegetables and fruits. Permutational multivariate analysis of variance revealed changes in β-diversity according to dietary patterns. In multivariable-adjusted models, the adherence to the vege pattern was positively correlated with α-diversity. This is the first study to reveal a correlation between intestinal microbiota and dietary habits rich in vegetables and fruits in a rural area of Japan.
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Affiliation(s)
- Toshitaka Yamauchi
- Innovation Division, KAGOME CO., LTD., 17 Nishitomiyama, Nasushiobara 329-2762, Japan
| | - Naoko Koyama
- Innovation Division, KAGOME CO., LTD., 17 Nishitomiyama, Nasushiobara 329-2762, Japan
| | - Ayumi Hirai
- Innovation Division, KAGOME CO., LTD., 17 Nishitomiyama, Nasushiobara 329-2762, Japan
| | - Hiroyuki Suganuma
- Innovation Division, KAGOME CO., LTD., 17 Nishitomiyama, Nasushiobara 329-2762, Japan
| | - Shigenori Suzuki
- Innovation Division, KAGOME CO., LTD., 17 Nishitomiyama, Nasushiobara 329-2762, Japan
| | - Koichi Murashita
- Innovation Center for Health Promotion, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan
| | - Tatsuya Mikami
- Innovation Center for Health Promotion, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan
| | - Yoshinori Tamada
- Innovation Center for Health Promotion, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan
| | - Noriaki Sato
- Human Genome Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
| | - Seiya Imoto
- Human Genome Center, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
| | - Ken Itoh
- Department of Vegetable Life Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
- Department of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan
| | - Shigeyuki Nakaji
- Innovation Center for Health Promotion, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan
- Department of Social Medicine, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan
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13
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Golpour F, Abbasi-Alaei M, Babaei F, Mirzababaei M, Parvardeh S, Mohammadi G, Nassiri-Asl M. Short chain fatty acids, a possible treatment option for autoimmune diseases. Biomed Pharmacother 2023; 163:114763. [PMID: 37105078 DOI: 10.1016/j.biopha.2023.114763] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/09/2023] [Accepted: 04/20/2023] [Indexed: 04/29/2023] Open
Abstract
Gut microbiota can interact with the immune system through its metabolites. Short-chain fatty acids (SCFAs), as one of the most abundant metabolites of the resident gut microbiota play an important role in this crosstalk. SCFAs (acetate, propionate, and butyrate) regulate nearly every type of immune cell in the gut's immune cell repertoire regarding their development and function. SCFAs work through several pathways to impose protection towards colonic health and against local or systemic inflammation. Additionally, SCFAs play a role in the regulation of immune or non-immune pathways that can slow the development of autoimmunity either systematically or in situ. The present study aims to summarize the current knowledge on the immunomodulatory roles of SCFAs and the association between the SCFAs and autoimmune disorders such as celiac disease (CD), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), type 1 diabetes (T1D) and other immune-mediated diseases, uncovering a brand-new therapeutic possibility to prevent or treat autoimmunity.
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Affiliation(s)
- Faezeh Golpour
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehrsa Abbasi-Alaei
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Babaei
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Mirzababaei
- Department of Clinical Biochemistry, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Siavash Parvardeh
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ghazaleh Mohammadi
- Cellular and Molecular Research Center, Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran; Department of Molecular Medicine, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
| | - Marjan Nassiri-Asl
- Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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14
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Crowder SL, Jim HSL, Hogue S, Carson TL, Byrd DA. Gut microbiome and cancer implications: Potential opportunities for fermented foods. Biochim Biophys Acta Rev Cancer 2023; 1878:188897. [PMID: 37086870 DOI: 10.1016/j.bbcan.2023.188897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 04/17/2023] [Accepted: 04/17/2023] [Indexed: 04/24/2023]
Abstract
There is a critical opportunity to improve response to immunotherapies and overall cancer survivorship via dietary interventions targeted to modify the gut microbiome, and in turn, potentially enhance anti-cancer immunity. A promising dietary intervention is fermented foods, which may alter gut microbiome composition and, in turn, improve immunity. In this article, we summarize the state of the literature pertaining to the gut microbiome and response to immunotherapy and other cancer treatments, potential clinical implications of utilizing a fermented foods dietary approach to improve cancer treatment outcomes, and existing gaps in the literature regarding the implementation of fermented food interventions among individuals with cancer or with a history of cancer. This review synthesizes a compelling rationale across different disciplines to lay a roadmap for future fermented food dietary intervention research aimed at modulating the gut microbiome to reduce cancer burden.
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Affiliation(s)
- Sylvia L Crowder
- Department of Health Outcomes and Behavior, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
| | - Heather S L Jim
- Department of Health Outcomes and Behavior, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Stephanie Hogue
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Tiffany L Carson
- Department of Health Outcomes and Behavior, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Doratha A Byrd
- Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
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15
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Rossi RE, Dispinzieri G, Elvevi A, Massironi S. Interaction between Gut Microbiota and Celiac Disease: From Pathogenesis to Treatment. Cells 2023; 12:cells12060823. [PMID: 36980164 PMCID: PMC10047417 DOI: 10.3390/cells12060823] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/24/2022] [Accepted: 01/01/2023] [Indexed: 03/09/2023] Open
Abstract
Celiac disease (CD) is a common systemic disorder that results from an abnormal response of human immunity to gluten intake, affecting the small intestine. In individuals who carry a genetic susceptibility, CD is triggered by environmental factors, including viral infections and dysbiosis of the gut microbiota. The gut microbiome is essential in controlling the immune system, and recent findings indicate that changes in the gut microbiome may contribute to various chronic immune disorders, such as CD through mechanisms that still require further exploration. Some bacteria exhibit epitopes that mimic gliadin and may enhance an immune response in the host. Other bacteria, including Pseudomonas aeruginosa, may work in conjunction with gluten to trigger and escalate intestinal inflammation. The microbiota may also directly influence antigen development through the production of immunogenic or tolerogenic gluten peptides or directly influence intestinal permeability through the release of zonulin. Finally, the gut microbiome can impact intestinal inflammation by generating proinflammatory or anti-inflammatory cytokines and metabolites. It is crucial to consider the impact of genetic factors (specifically, HLA-DQ haplotypes), perinatal elements such as birth mode, type of infant feeding, and antibiotic and infection exposure on the composition of the early intestinal microbiome. According to the available studies, the gut microbiome alterations associated with CD tend to exhibit a decreased presence of beneficial bacteria, including some anti-inflammatory Bifidobacterium species. However, some controversy remains as some reports have found no significant differences between the gut microbiomes of individuals with and without CD. A better understanding of the gut microbiome’s role in the development of CD would greatly benefit both prevention and treatment efforts, especially in complicated or treatment-resistant cases. Here, we have attempted to summarize the available evidence on the relationship between the gut microbiota and CD, with a particular focus on potential therapeutic targets.
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Affiliation(s)
- Roberta Elisa Rossi
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089 Milan, Italy
| | - Giulia Dispinzieri
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca and European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy
- Correspondence: ; Tel.: +39-039-2332317; Fax: +39-039-2300129
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16
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Fenneman AC, Weidner M, Chen LA, Nieuwdorp M, Blaser MJ. Antibiotics in the pathogenesis of diabetes and inflammatory diseases of the gastrointestinal tract. Nat Rev Gastroenterol Hepatol 2023; 20:81-100. [PMID: 36258032 PMCID: PMC9898198 DOI: 10.1038/s41575-022-00685-9] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/01/2022] [Indexed: 02/06/2023]
Abstract
Antibiotic use is increasing worldwide. However, the use of antibiotics is clearly associated with changes in gut microbiome composition and function, and perturbations have been identified as potential environmental risk factors for chronic inflammatory disorders of the gastrointestinal tract. In this Review, we examine the association between the use of antibiotics and the onset and development of both type 1 and type 2 diabetes, inflammatory bowel disease, including ulcerative colitis and Crohn's disease, as well as coeliac disease and eosinophilic oesophagitis. We discuss the key findings of epidemiological studies, provide mechanistic insights into the pathways by which the gut microbiota might contribute to these diseases, and assess clinical trials investigating the effects of antibiotics. Such studies indicate that antibiotic exposures, varying in type, timing and dosage, could explain differences in disease risk. There seems to be a critical window in early life in which perturbation of the microbiome has a substantial effect on disease development. Identifying the antibiotic-perturbed gut microbiota as a factor that contributes to the pathophysiology of these inflammatory disorders might stimulate new approaches to prevention, diagnosis and treatment.
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Affiliation(s)
- Aline C Fenneman
- Department of Clinical and Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Melissa Weidner
- Department of Paediatrics, Rutgers University, New Brunswick, NJ, USA
| | - Lea Ann Chen
- Department of Medicine, Rutgers University, New Brunswick, NJ, USA
| | - Max Nieuwdorp
- Department of Clinical and Experimental Vascular Medicine, Amsterdam Cardiovascular Sciences (ACS), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
- Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM), Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Martin J Blaser
- Department of Medicine, Rutgers University, New Brunswick, NJ, USA.
- Department of Pathology and Laboratory Medicine, Rutgers University, New Brunswick, NJ, USA.
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17
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Subchronic Oral Cylindrospermopsin Exposure Alters the Host Gut Microbiome and Is Associated with Progressive Hepatic Inflammation, Stellate Cell Activation, and Mild Fibrosis in a Preclinical Study. Toxins (Basel) 2022; 14:toxins14120835. [PMID: 36548732 PMCID: PMC9785749 DOI: 10.3390/toxins14120835] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/20/2022] [Accepted: 11/21/2022] [Indexed: 12/02/2022] Open
Abstract
Epidemiological studies have reported a strong association between liver injury and incidences of hepatocellular carcinoma in sections of humans globally. Several preclinical studies have shown a strong link between cyanotoxin exposure and the development of nonalcoholic steatohepatitis, a precursor of hepatocellular carcinoma. Among the emerging threats from cyanotoxins, new evidence shows cylindrospermopsin release in freshwater lakes. A known hepatotoxin in higher concentrations, we examined the possible role of cylindrospermopsin in causing host gut dysbiosis and its association with liver pathology in a mouse model of toxico-pharmacokinetics and hepatic pathology. The results showed that oral exposure to cylindrospermopsin caused decreased diversity of gut bacteria phyla accompanied by an increased abundance of Clostridioides difficile and decreased abundance of probiotic flora such as Roseburia, Akkermanssia, and Bacteroides thetaiotamicron, a signature most often associated with intestinal and hepatic pathology and underlying gastrointestinal disease. The altered gut dysbiosis was also associated with increased Claudin2 protein in the intestinal lumen, a marker of gut leaching and endotoxemia. The study of liver pathology showed marked liver inflammation, the release of damage-associated molecular patterns, and activation of toll-like receptors, a hallmark of consistent and progressive liver damage. Hepatic pathology was also linked to increased Kupffer cell activation and stellate cell activation, markers of progressive liver damage often linked to the development of liver fibrosis and carcinoma. In conclusion, the present study provides additional evidence of cylindrospermopsin-linked progressive liver pathology that may be very well-linked to gut dysbiosis, though definitive evidence involving this link needs to be studied further.
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18
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Molecular Characterization of Shiga Toxin Produced by Escherichia coli Isolated from Milk Samples in Baghdad City. JOURNAL OF PURE AND APPLIED MICROBIOLOGY 2022. [DOI: 10.22207/jpam.16.3.76] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Raw milk is a nutrient-rich food that is considered a high-quality nutritional medium for many microorganism, including Escherichia coli. The aim of the present work was the diagnosis, by molecular methods, of Shiga toxins produced by E. coli strains isolated from cow milk samples collected from different farms in Al-Mahmmodia, Al yoosifya, Al lattiffya, Al howasha, and Arab Jboor in the government of Baghdad during the summer season. Milk samples were incubated in media for bacterial isolation. Isolates were identified using Gram staining and biochemical tests. Out of 50 samples, 15 (30%) showed the presence of E. coli. To confirm the identity of the isolates, their 16S rRNA genes were amplified using specific primers. The results showed that all isolates were E. coli. Shiga toxin-producing E. coli (STEC) were detected among the samples. The prevalence of stx1 genes was higher than that of stx2 among them. No STECs were found among six of the sample isolates, and none of these isolates was positive for stx1 and stx2. SDS-PAGE was used to determine the molecular weight of the toxin, and four selected E. coli bacteria producing Shiga-like toxins showed a clear band of approximately 70 kDa.
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19
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Khoshbayan A, Golmoradi Zadeh R, Taati Moghadam M, Mirkalantari S, Darbandi A. Molecular determination of O25b/ST131 clone type among extended spectrum β-lactamases production Escherichia coli recovering from urinary tract infection isolates. Ann Clin Microbiol Antimicrob 2022; 21:35. [PMID: 35927655 PMCID: PMC9351160 DOI: 10.1186/s12941-022-00526-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 07/22/2022] [Indexed: 11/10/2022] Open
Abstract
Background Escherichia coli (E. coli) O25b/ST131 clone causes urinary tract infection (UTI) and is associated with a broad spectrum of other infections, such as intra-abdominal and soft tissue infections, that can be affecting bloodstream infections. Therefore, since O25b/ST131 has been reported in several studies from Iran, in the current study, we have investigated the molecular characteristics, typing, and biofilm formation of O25b/ST131 clone type E. coli collected from UTI specimens. Methods A total of 173 E. coli isolates from UTI were collected. The susceptibility to all fourth generations of cephalosporins (cefazolin, cefuroxime, ceftriaxone, cefotaxime, ceftazidime, cefepime) and ampicillin, ampicillin-sulbactam and aztreonam was determined. Class A ESBLs, class D ESBL and the presence of pabB gene screenings to detect of O25b/ST131 clone type were performed by using of PCR. Biofilm formation was compared between O25b/ST131 isolates and non-O25b/ST131 isolates. Finally, ERIC-PCR was used for typing of ESBL positive isolates. Results Ninety-four ESBL positive were detected of which 79 of them were O25b/ST131. Antimicrobial susceptibility test data showed that most antibiotics had a higher rate of resistance in isolates of the O25b/ST131 clonal type. Biofilm formation showed that there was a weak association between O25b/ST131 clone type isolates and the level of the biofilm formation. ERIC-PCR results showed that E. coli isolates were genetically diverse and classified into 14 groups. Conclusion Our results demonstrated the importance and high prevalence of E. coli O25b/ST131 among UTI isolates with the ability to spread fast and disseminate antibiotic resistance genes.
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Affiliation(s)
- Amin Khoshbayan
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Rezvan Golmoradi Zadeh
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Majid Taati Moghadam
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Shiva Mirkalantari
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. .,Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.
| | - Atieh Darbandi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.,Antimicrobial Resistance Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
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20
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Palmieri O, Castellana S, Bevilacqua A, Latiano A, Latiano T, Panza A, Fontana R, Ippolito AM, Biscaglia G, Gentile A, Gioffreda D, Decina I, Tricarico M, Sinigaglia M, Corbo MR, Mazza T, Perri F, Lamacchia C. Adherence to Gluten-Free Diet Restores Alpha Diversity in Celiac People but the Microbiome Composition Is Different to Healthy People. Nutrients 2022; 14:nu14122452. [PMID: 35745182 PMCID: PMC9228530 DOI: 10.3390/nu14122452] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/09/2022] [Accepted: 06/09/2022] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is an autoimmune disease with the destruction of small intestinal villi, which occurs in genetically predisposed individuals. At the present moment, a gluten-free diet (GFD) is the only way to restore the functionality of gut mucosa. However, there is an open debate on the effects of long-term supplementation through a GFD, because some authors report an unbalance in microbial taxa composition. Methods: For microbiome analysis, fecal specimens were collected from 46 CD individuals in GFD for at least 2 years and 30 specimens from the healthy controls (HC). Data were analyzed using an ensemble of software packages: QIIME2, Coda-lasso, Clr-lasso, Selbal, PICRUSt2, ALDEx2, dissimilarity-overlap analysis, and dysbiosis detection tests. Results: The adherence to GFD restored the alpha biodiversity of the gut microbiota in celiac people but microbial composition at beta diversity resulted as different to HC. The microbial composition of the CD subjects was decreased in a number of taxa, namely Bifidobacterium longum and several belonging to Lachnospiraceae family, whereas Bacteroides genus was found to be more abundant. Predicted metabolic pathways among the CD bacterial communities revealed an important role in tetrapyrrole biosynthesis. Conclusions: CD patients in GFD had a non-dysbiotic microbial composition for the crude alpha diversity metrics. We found significant differences in beta diversity, in certain taxon, and pathways between subjects with inactive CD in GFD and controls. Collectively, our data may suggest the development of new GFD products by modulating the gut microbiota through diet, supplements of vitamins, and the addition of specific prebiotics.
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Affiliation(s)
- Orazio Palmieri
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
- Correspondence:
| | - Stefano Castellana
- Bioinformatics Unit, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (S.C.); (T.M.)
| | - Antonio Bevilacqua
- Department of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, 71122 Foggia, Italy; (A.B.); (M.S.); (M.R.C.); (C.L.)
| | - Anna Latiano
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
| | - Tiziana Latiano
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
| | - Anna Panza
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
| | - Rosanna Fontana
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
| | - Antonio Massimo Ippolito
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
| | - Giuseppe Biscaglia
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
| | - Annamaria Gentile
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
| | - Domenica Gioffreda
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
| | - Ivana Decina
- New Gluten World s.r.l., 71121 Foggia, Italy; (I.D.); (M.T.)
| | | | - Milena Sinigaglia
- Department of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, 71122 Foggia, Italy; (A.B.); (M.S.); (M.R.C.); (C.L.)
| | - Maria Rosaria Corbo
- Department of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, 71122 Foggia, Italy; (A.B.); (M.S.); (M.R.C.); (C.L.)
| | - Tommaso Mazza
- Bioinformatics Unit, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (S.C.); (T.M.)
| | - Francesco Perri
- Division of Gastroenterology, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy; (A.L.); (T.L.); (A.P.); (R.F.); (A.M.I.); (G.B.); (A.G.); (D.G.); (F.P.)
| | - Carmela Lamacchia
- Department of Agriculture, Food, Natural Resources and Engineering (DAFNE), University of Foggia, 71122 Foggia, Italy; (A.B.); (M.S.); (M.R.C.); (C.L.)
- New Gluten World s.r.l., 71121 Foggia, Italy; (I.D.); (M.T.)
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21
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Kaliciak I, Drogowski K, Garczyk A, Kopeć S, Horwat P, Bogdański P, Stelmach-Mardas M, Mardas M. Influence of Gluten-Free Diet on Gut Microbiota Composition in Patients with Coeliac Disease: A Systematic Review. Nutrients 2022; 14:nu14102083. [PMID: 35631222 PMCID: PMC9147811 DOI: 10.3390/nu14102083] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/10/2022] [Accepted: 05/13/2022] [Indexed: 02/06/2023] Open
Abstract
The aim of this study was to assess the changes in microbiota composition during a gluten-free diet (GFD) in coeliac disease (CD) patients. The systematic search followed databases such as PUBMED (MEDLINE), SCOPUS, WEB OF SCIENCE and EMBASE. Out of 843 initially screened papers, a total number of 13 research papers were included. A total of 212 patients with CD on GFD, in comparison to 174 healthy individuals and 176 untreated patients with CD, were examined. Analysis of the microbial community based primarily on faecal samples and duodenal biopsies. Bifidobacterium was noticed to be less abundant in the study group than in both control groups, while the abundance of Bacteroides was more numerous in the group of CD patients on GFD. Staphylococcaceae prevailed in untreated CD patients. Despite the fact that the GFD was not able to fully restore commensal microorganism abundance, the treatment was associated with the greater abundance of selected beneficial bacteria and lower presence of pathogenic bacteria associated with worsening of CD symptoms.
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Affiliation(s)
- Iwona Kaliciak
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 60-569 Poznan, Poland; (I.K.); (K.D.); (A.G.); (S.K.); (P.H.); (P.B.)
| | - Konstanty Drogowski
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 60-569 Poznan, Poland; (I.K.); (K.D.); (A.G.); (S.K.); (P.H.); (P.B.)
| | - Aleksandra Garczyk
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 60-569 Poznan, Poland; (I.K.); (K.D.); (A.G.); (S.K.); (P.H.); (P.B.)
| | - Stanisław Kopeć
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 60-569 Poznan, Poland; (I.K.); (K.D.); (A.G.); (S.K.); (P.H.); (P.B.)
| | - Paulina Horwat
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 60-569 Poznan, Poland; (I.K.); (K.D.); (A.G.); (S.K.); (P.H.); (P.B.)
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 60-569 Poznan, Poland; (I.K.); (K.D.); (A.G.); (S.K.); (P.H.); (P.B.)
| | - Marta Stelmach-Mardas
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 60-569 Poznan, Poland; (I.K.); (K.D.); (A.G.); (S.K.); (P.H.); (P.B.)
- Correspondence: ; Tel.: +48-697-424-245
| | - Marcin Mardas
- Department of Gynecological Oncology, Institute of Oncology, Poznan University of Medical Sciences, 60-569 Poznan, Poland;
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22
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Shah MF, Al Mamun MA, Hossain MT, Moniruzzaman M, Yeasmine S, Uddin MH, Jasim Uddin M. Clearance of Escherichia coli by the freshwater mussel Lamellidens marginalis in laboratory conditions. MOLLUSCAN RESEARCH 2022. [DOI: 10.1080/13235818.2022.2070101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Md. Firoz Shah
- Department of Fisheries Management, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Md. Abdullah Al Mamun
- Department of Fisheries Management, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | | | | | - Selina Yeasmine
- Freshwater Station, Bangladesh Fisheries Research Institute, Mymensingh, Bangladesh
| | - Md. Helal Uddin
- Department of Fisheries Management, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - M. Jasim Uddin
- Department of Fisheries Management, Bangladesh Agricultural University, Mymensingh, Bangladesh
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23
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Upadhyay D, Das P, Dattagupta S, Makharia GK, Jagannathan NR, Sharma U. NMR based metabolic profiling of patients with potential celiac disease elucidating early biochemical changes of gluten-sensitivity: A pilot Study. Clin Chim Acta 2022; 531:291-301. [PMID: 35489390 DOI: 10.1016/j.cca.2022.04.999] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/07/2022] [Accepted: 04/25/2022] [Indexed: 11/15/2022]
Abstract
BACKGROUND The patients with positive celiac disease (CeD) specific serology, but no evidence of intestinal inflammation are defined as potential celiac disease (PCeD) patients. About one-third of PCeD patients develop intestinal inflammation over time. The present study investigated the metabolome of small intestinal biopsies, blood plasma, and urine of patients with PCeD to understand the biochemical changes underlying the CeD. METHODS The metabolic profiles of small intestinal biopsies, blood plasma, and urine of patients with PCeD (n=7) were compared with CeD (n=64) and controls (n=15) [disease controls (DC) and healthy controls (HC)] using 1H NMR spectroscopy. RESULTS The intestinal mucosa of PCeD showed lower levels of histidine, glycine, tyrosine, and tryptophan compared to DC. Altered levels of 6 metabolites (glucose, acetate, acetoacetate, β-hydroxybutyrate, pyruvate, arginine) in blood plasma and two metabolites (succinate and aminohippurate) in urine were observed in PCeD compared to HC. The PLS-DA model built on the concentration of blood plasma showed separate clustering for PCeD and CeD patients. CONCLUSION Altered metabolic profile of PCeD suggested that gluten intolerance was evident at the metabolic level before the intestinal damage. Altered energy metabolism and lower cytoprotective activity (histidine, glycine, arginine) indicated vulnerability to develop intestinal inflammation in PCeD over time. Our study may provide an insight into early biochemical processes of the progression of PCeD to CeD.
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Affiliation(s)
- Deepti Upadhyay
- Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi -110 029, India
| | - Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, New Delhi -110 029, India
| | - Siddhartha Dattagupta
- Department of Pathology, All India Institute of Medical Sciences, New Delhi -110 029, India
| | - Govind K Makharia
- Department of Gastroenterology & Human Nutrition, All India Institute of Medical Sciences, New Delhi -110 029, India
| | | | - Uma Sharma
- Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi -110 029, India.
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24
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Nafady MH, Sayed ZS, Abdelkawy DA, Shebl ME, Elsayed RA, Ashraf GM, Perveen A, Attia MS, Bahbah EI. The Effect of Gut Microbe Dysbiosis on the Pathogenesis of Alzheimer's Disease (AD) and related conditions. Curr Alzheimer Res 2022; 19:274-284. [PMID: 35440296 DOI: 10.2174/1567205019666220419101205] [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: 12/30/2021] [Revised: 02/17/2022] [Accepted: 03/09/2022] [Indexed: 11/22/2022]
Abstract
It has been hypothesized that the shift in gut microbiota composition, known as gut microbe dysbiosis, may be correlated with the onset of Alzheimer's disease (AD), which is the most common cause of dementia characterized by a gradual deterioration in cognitive function associated with the development of amyloid-beta (Aβ) plaques. The gut microbiota dysbiosis induces the release of significant amounts of amyloids, lipopolysaccharides, and neurotoxins, which might play a role in modulating signaling pathways and immune activation, leading to the production of proinflammatory cytokines related to the pathogenesis of AD. The dysbiosis of gut microbe is associated with various diseases such as type 2 diabetes, obesity, hypertension, and some neuropsychiatric disorders like depression, anxiety, and stress. It is conceivable that these diseases trigger the onset of AD. Thus, modifying the gut microbiota composition with probiotic and prebiotic supplementation can reduce depression and anxiety symptoms, lower stress reactivity, and improve memory. This narrative review aimed to examine the possible role of gut microbe dysbiosis in AD's pathogenesis.
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Affiliation(s)
- Mohamed H Nafady
- Radiological Imaging Technology Department, Faculty of Applied Medical Science, Misr university for science and technology (MUST), Cairo, Egypt.,Radiation Science Department, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Zeinab S Sayed
- Faculty of Applied Medical Science (AMS), Misr university for science and technology (MUST), Cairo, Egypt
| | - Dalia A Abdelkawy
- Faculty of Applied Medical Science (AMS), Misr university for science and technology (MUST), Cairo, Egypt
| | - Mostafa E Shebl
- Faculty of Applied Medical Science (AMS), Misr university for science and technology (MUST), Cairo, Egypt
| | - Reem A Elsayed
- Faculty of Applied Medical Science (AMS), Misr university for science and technology (MUST), Cairo, Egypt
| | - Ghulam Md Ashraf
- Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.,Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Asma Perveen
- Glocal School of Life Sciences, Glocal University, Mirzapur Pole, Saharanpur, Uttar Pradesh, India
| | - Mohamed S Attia
- Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt
| | - Eshak I Bahbah
- Faculty of Medicine, Al-Azhar University, Damietta, Egypt.,Medical Research Group of Egypt (MRGE), Cairo, Egypt.,SevoClin Research Group, Cairo, Egypt
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25
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Hartmann P. Editorial: The Microbiome in Hepatobiliary and Intestinal Disease. Front Physiol 2022; 13:893074. [PMID: 35492588 PMCID: PMC9044070 DOI: 10.3389/fphys.2022.893074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 03/11/2022] [Indexed: 12/12/2022] Open
Affiliation(s)
- Phillipp Hartmann
- Department of Pediatrics, University of California, San Diego, San Diego, CA, United States
- Division of Gastroenterology, Hepatology and Nutrition, Rady Children’s Hospital San Diego, San Diego, CA, United States
- *Correspondence: Phillipp Hartmann,
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26
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López-Siles M, Camprubí-Font C, Gómez Del Pulgar EM, Sabat Mir M, Busquets D, Sanz Y, Martinez-Medina M. Prevalence, Abundance, and Virulence of Adherent-Invasive Escherichia coli in Ulcerative Colitis, Colorectal Cancer, and Coeliac Disease. Front Immunol 2022; 13:748839. [PMID: 35359974 PMCID: PMC8960851 DOI: 10.3389/fimmu.2022.748839] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 01/31/2022] [Indexed: 01/08/2023] Open
Abstract
Background & Aims Adherent-invasive E. coli (AIEC) has largely been implicated in the pathogenesis of Crohn’s disease (CD). E. coli strains with similar genetic backgrounds and virulence genes profiles have been associated with other intestinal disorders, such as ulcerative colitis (UC), colorectal cancer (CRC), and coeliac disease (CeD), but the role of AIEC in these diseases remains unexplored. We aimed to assess the distribution, abundance, and pathogenic features of AIEC in UC, CRC, and CeD. Methods The AIEC phenotype was investigated in 4,233 E. coli isolated from the ileum and colon of 14 UC and 15 CRC patients and in 38 fecal E. coli strains obtained from 17 CeD and 10 healthy (H) children. AIEC prevalence and abundance were compared with previous data from CD patients and H controls. Clonality, virulence gene carriage, and phylogenetic origin were determined for the AIEC identified. Results In UC, AIEC prevalence was intermediate between CD and H subjects (UC: 35.7%, CD: 55.0%, H: 21.4%), and similar to CD patients with colonic disease (C-CD: 40.0%). In CRC, the prevalence was lower (6.7%) than these groups. In patients with AIEC, the estimated abundance was similar across all intestinal conditions. All AIEC strains isolated from UC and CRC belonged to the B1 phylogroup, except for a strain of the A phylogroup, and the majority (75% of clonally distinct AIEC) harbored the Afa/Dr operon and the cdt gene. None of the E. coli isolated from the CeD cohort were AIEC. Nonetheless, E. coli strains isolated from active CeD patients showed higher invasion indices than those isolated from H and inactive CeD pediatric patients. Conclusion We support the hypothesis that AIEC-like strains can be involved not only in CD but also in UC. Further works are needed to study the virulence particularities of these groups of strains and to determine if there is a causative link between AIEC and UC. In contrast, we rule out the possible association of AIEC with CRC. In addition, to further study the E. coli strains in CeD for their possible pathogenic role would be of interest.
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Affiliation(s)
- Mireia López-Siles
- Microbiology of Intestinal Diseases, Biology Department, Universitat de Girona, Girona, Spain
| | - Carla Camprubí-Font
- Microbiology of Intestinal Diseases, Biology Department, Universitat de Girona, Girona, Spain
| | - Eva M Gómez Del Pulgar
- Instituto de Agroquímica y Tecnología de Alimentos, Spanish National Research Council (CSIC), Paterna, Spain
| | - Miriam Sabat Mir
- Department of Gastroenterology, Hospital Santa Caterina, Salt, Spain
| | - David Busquets
- Department of Gastroenterology, Hospital Universitari Doctor Josep Trueta, Girona, Spain
| | - Yolanda Sanz
- Instituto de Agroquímica y Tecnología de Alimentos, Spanish National Research Council (CSIC), Paterna, Spain
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27
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Liu ZZ, Sun JH, Wang WJ. Gut microbiota in gastrointestinal diseases during pregnancy. World J Clin Cases 2022; 10:2976-2989. [PMID: 35647135 PMCID: PMC9082698 DOI: 10.12998/wjcc.v10.i10.2976] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 07/18/2021] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota (GM) is a micro-ecosystem composed of all microorganisms in the human intestine. The interaction between GM and the host plays an important role in maintaining normal physiological functions in the host. Dysbiosis of the GM may cause various diseases. GM has been demonstrated to be associated with human health and disease, and changes during individual development and disease. Pregnancy is a complicated physiological process. Hormones, the immune system, metabolism, and GM undergo drastic changes during pregnancy. Gastrointestinal diseases during pregnancy, such as hepatitis, intrahepatic cholestasis of pregnancy, and pre-eclampsia, can affect both maternal and fetal health. The dysregulation of GM during pregnancy may lead to a variety of diseases, including gastrointestinal diseases. Herein, we review recent research articles on GM in pregnancy-related gastrointestinal diseases, discuss the interaction of the GM with the host under normal physiological conditions, gastrointestinal diseases, and pregnancy-specific disorders. As more attention is paid to reproductive health, the pathogenic mechanism of GM in gastrointestinal diseases during pregnancy will be further studied to provide a theoretical basis for the use of probiotics to treat these diseases.
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Affiliation(s)
- Zhong-Zhen Liu
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
| | - Jing-Hua Sun
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Wen-Jing Wang
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
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28
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Robeson MS, Manna K, Randolph C, Byrum S, Hakkak R. Short-Term Metformin Treatment Enriches Bacteroides dorei in an Obese Liver Steatosis Zucker Rat Model. Front Microbiol 2022; 13:834776. [PMID: 35432282 PMCID: PMC9006818 DOI: 10.3389/fmicb.2022.834776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 03/07/2022] [Indexed: 11/29/2022] Open
Abstract
Obesity is the leading cause of health-related diseases in the United States and World. Previously, we reported that obesity can change gut microbiota using the Zucker rat model. Metformin is an oral anti-hyperglycemic agent approved by the FDA to treat type 2 diabetes (T2D) in adults and children older than 10 years of age. The correlation of short-term metformin treatment and specific alterations to the gut microbiota in obese models is less known. Short-term metformin has been shown to reduce liver steatosis. Here we investigate the effects of short-term metformin treatment on population of gut microbiota profile in an obese rat model. Five week old obese (n = 12) female Zucker rats after 1 week of acclimation, received AIN-93 G diet for 8 weeks and then rats were randomly assigned into two groups (6 rats/group): (1) obese without metformin (ObC), or (2) obese with metformin (ObMet). Metformin was mixed with AIN-93G diet at 1,000 mg/kg of diet. Rats were weighed twice per week. All rats were sacrificed at the end of metformin treatment at 10 weeks and fecal samples were collected and kept at -80°C. Total microbial DNA was collected directly from the fecal samples used for shotgun-metagenomics sequencing and subsequently analyzed using MetaPlAn and HUMAnN. After stringent data filtering and quality control we found significant differences (p = 0.0007) in beta diversity (Aitchison distances) between the ObC vs. ObMet groups. Supervised and unsupervised analysis of the log-ratios Bacteroides dorei and B. massiliensis vs. all other Bacteroides spp., revealed that B. dorei and B. massiliensis were enriched in the ObMet group, while the remaining Bacteroides spp. where enriched in the ObC group (p = 0.002). The contributional diversity of pathways is also significantly associated by treatment group (p = 0.008). In summary, in the obese Zucker rat model, short-term metformin treatment changes the gut microbiota profile, particularly altering the composition Bacteroides spp. between ObC and ObMet.
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Affiliation(s)
- Michael S. Robeson
- Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Kanishka Manna
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | | | - Stephanie Byrum
- Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Reza Hakkak
- Arkansas Children’s Research Institute, Little Rock, AR, United States
- Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR, United States
- Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States
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29
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Khoshbayan A, Shariati A, Razavi S, Baseri Z, Ghodousi A, Darban-Sarokhalil D. Mutation in mgrB is the major colistin resistance mechanism in Klebsiella pneumoniae clinical isolates in Tehran, Iran. Acta Microbiol Immunol Hung 2022; 69:61-67. [PMID: 35113039 DOI: 10.1556/030.2022.01679] [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: 12/08/2021] [Accepted: 01/03/2022] [Indexed: 12/22/2022]
Abstract
Colistin is considered as one of a last resort antimicrobial agent against multidrug-resistant Gram-negative bacteria including Escherichia coli and Klebsiella pneumoniae. However, the recent emergence of colistin resistance (ColR) worldwide that severely restricts therapeutic options is a serious threat to global public health. In this study we have investigated the molecular determinants in ColR K. pneumoniae isolates collected from clinical specimens. A total of 98 E. coli and 195 K. pneumoniae clinical isolates were collected from two hospitals from August 2018 to December 2019 in Tehran, Iran. Colistin susceptibility and minimum inhibitory concentrations (MIC) were determined according to the Clinical and Laboratory Standards Institute by disk diffusion method, and microdilution method, respectively. For isolates with colistin MIC ≥4 μg mL-1, PCR was performed for the detection of mcr-1 to mcr-4 genes. Moreover, nucleotide sequences of mgrB, phoP, phoQ, pmrA, and pmrB genes were determined by sequencing. Finally, the transcriptional level of pmrK and pmrC genes was evaluated by quantitative reverse transcription PCR (RT-qPCR). None of the E. coli isolates were resistant to colistin while 21 out 195 K. pneumoniae isolates were identified as resistant, 19 of which carried mutation in the mgrB gene. Three different mutations were observed in the pmrB gene in 3 K. pneumoniae isolates. None of the ColR isolates showed alternations in pmrA, phoP, and phoQ genes. Furthermore, none of the plasmid-encoding genes were detected. Transcriptional level of the pmrK gene increased in all ColR isolates meanwhile, pmrC overexpression was detected in 16 out 21 (76.19%) isolates. Eventually, all ColR isolates were susceptible to tigecycline. Our results demonstrated that the alternation of mgrB gene is the main mechanism related to colistin resistance among ColR K. pneumoniae isolates in this study.
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Affiliation(s)
- Amin Khoshbayan
- 1 Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Aref Shariati
- 2 Molecular and Medicine Research Center, Khomein University of Medical Sciences, Khomein, Iran
| | - Shabnam Razavi
- 1 Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zohre Baseri
- 3 Department of Pathology and Laboratory Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Arash Ghodousi
- 4 Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University, Milan, Italy
| | - Davood Darban-Sarokhalil
- 1 Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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30
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Aboulaghras S, Piancatelli D, Oumhani K, Balahbib A, Bouyahya A, Taghzouti K. Pathophysiology and immunogenetics of celiac disease. Clin Chim Acta 2022; 528:74-83. [PMID: 35120899 DOI: 10.1016/j.cca.2022.01.022] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/20/2022] [Accepted: 01/28/2022] [Indexed: 02/08/2023]
Abstract
Celiac disease (CD) is a chronic inflammatory enteropathy caused by gluten (protein from wheat, rye and, barley) in genetically predisposed individuals carrying the HLA-DQ2/HLA-DQ8 genotype. This pathology has a multifactorial etiology in which HLA genes, the microbiome, gluten and, other environmental factors are involved in the development of the disease. Its pathogenesis involves both innate and adaptive immunity as well as upregulation of IL-15. The objective of this review is to examine the results of current studies on genetic and environmental variables to better understand the pathogenesis of this enteropathy. The complex etiology of celiac disease makes our understanding of the pathogenesis of the disease incomplete, and a better knowledge of the many genetic and environmental components would help us better understand the pathophysiology of celiac disease.
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Affiliation(s)
- Sara Aboulaghras
- Physiology and Physiopathology Team, Faculty of Sciences, Genomic of Human Pathologies Research, Mohammed V University in Rabat, Morocco; Laboratoire d'Immunologie, Institut National d'Hygiene, Rabat, Morocco
| | - Daniela Piancatelli
- National Research Council (CNR)-Institute of Translational Pharmacology (IFT), L'Aquila, Italy
| | - Khadija Oumhani
- Laboratoire d'Immunologie, Institut National d'Hygiene, Rabat, Morocco
| | - Abdelaali Balahbib
- Laboratory of Zoology and General Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco
| | - Abdelhakim Bouyahya
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Genomic Center of Human Pathologies Research, Mohammed V University in Rabat, Rabat, Morocco.
| | - Khalid Taghzouti
- Physiology and Physiopathology Team, Faculty of Sciences, Genomic of Human Pathologies Research, Mohammed V University in Rabat, Morocco
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31
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Fecal Microbiota Transplants for Inflammatory Bowel Disease Treatment: Synthetic- and Engineered Communities-Based Microbiota Transplants Are the Future. Gastroenterol Res Pract 2022; 2022:9999925. [PMID: 35140783 PMCID: PMC8820897 DOI: 10.1155/2022/9999925] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 01/12/2022] [Indexed: 12/21/2022] Open
Abstract
The human intestine harbors a huge number of diverse microorganisms where a variety of complex interactions take place between the microbes as well as the host and gut microbiota. Significant long-term variations in the gut microbiota (dysbiosis) have been associated with a variety of health conditions including inflammatory bowel disease (IBD). Conventional fecal microbiota transplantations (FMTs) have been utilized to treat IBD and have been proved promising. However, various limitations such as transient results, pathogen transfer, storage, and reproducibility render conventional FMT less safe and less sustainable. Defined synthetic microbial communities (SynCom) have been used to dissect the host-microbiota-associated functions using gnotobiotic animals or in vitro cell models. This review focuses on the potential use of SynCom in IBD and its advantages and relative safety over conventional FMT. Additionally, this review reinforces how various technological advances could be combined with SynCom to have a better understanding of the complex microbial interactions in various gut inflammatory diseases including IBD. Some technological advances including the availability of a gut-on-a-chip system, intestinal organoids, ex vivo intestinal cultures, AI-based refining of the microbiome structural and functional data, and multiomic approaches may help in making more practical in vitro models of the human host. Additionally, an increase in the cultured diversity from gut microbiota and the availability of their genomic information would further make the design and utilization of SynCom more feasible. Taken together, the combined use of the available knowledge of the gut microbiota in health and disease and recent technological advances and the development of defined SynCom seem to be a promising, safe, and sustainable alternative to conventional FMT in treating IBD.
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32
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Singh A, Kaur H, Midha V, Sood A. Microorganisms in the Pathogenesis and Management of Celiac Disease (CeD). ROLE OF MICROORGANISMS IN PATHOGENESIS AND MANAGEMENT OF AUTOIMMUNE DISEASES 2022:287-307. [DOI: 10.1007/978-981-19-4800-8_15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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33
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Rej A, Sanders D. Irritable bowel syndrome. COELIAC DISEASE AND GLUTEN-RELATED DISORDERS 2022:247-261. [DOI: 10.1016/b978-0-12-821571-5.00010-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Xu D, Li L, Tang X, Chen J, Yan W, Wang L, Zhang X, Li B, Yao H. Potential prebiotic functions of a characterised
Ehretia macrophylla
Wall. fruit polysaccharide. Int J Food Sci Technol 2022. [DOI: 10.1111/ijfs.15005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Dan Xu
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety School of Food Science and Engineering South China University of Technology 381 Wushan Road, Tianhe District Guangzhou 510640 China
| | - Lin Li
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety School of Food Science and Engineering South China University of Technology 381 Wushan Road, Tianhe District Guangzhou 510640 China
- School of Chemical Engineering and Energy Technology Dongguan University of Technology College Road 1 Dongguan 523808 China
| | - Xin Tang
- Department of Food Science and Engineering Jinan University Guangzhou 510632 China
| | - Juncheng Chen
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety School of Food Science and Engineering South China University of Technology 381 Wushan Road, Tianhe District Guangzhou 510640 China
| | - Wenbing Yan
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety School of Food Science and Engineering South China University of Technology 381 Wushan Road, Tianhe District Guangzhou 510640 China
| | - Lei Wang
- Department of Food Science and Engineering Jinan University Guangzhou 510632 China
| | - Xia Zhang
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety School of Food Science and Engineering South China University of Technology 381 Wushan Road, Tianhe District Guangzhou 510640 China
| | - Bing Li
- Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety School of Food Science and Engineering South China University of Technology 381 Wushan Road, Tianhe District Guangzhou 510640 China
| | - Hong Yao
- Centre for Nutrition and Food Sciences Queensland Alliance for Agriculture and Food Innovation The University of Queensland St Lucia Qld 4072 Australia
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35
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Chronic Intestinal Pseudo-Obstruction: Is There a Connection with Gut Microbiota? Microorganisms 2021; 9:microorganisms9122549. [PMID: 34946150 PMCID: PMC8703706 DOI: 10.3390/microorganisms9122549] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/06/2021] [Accepted: 12/07/2021] [Indexed: 12/23/2022] Open
Abstract
Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome characterized by severe impairment of gastrointestinal (GI) motility, and its symptoms are suggestive of partial or complete intestinal obstruction in the absence of any lesion restricting the intestinal lumen. Diagnosis and therapy of CIPO patients still represent a significant challenge for clinicians, despite their efforts to improve diagnostic workup and treatment strategies for this disease. The purpose of this review is to better understand what is currently known about the relationship between CIPO patients and intestinal microbiota, with a focus on the role of the enteric nervous system (ENS) and the intestinal endocrine system (IES) in intestinal motility, underling the importance of further studies to deeply understand the causes of gut motility dysfunction in these patients.
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36
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Wu X, Qian L, Liu K, Wu J, Shan Z. Gastrointestinal microbiome and gluten in celiac disease. Ann Med 2021; 53:1797-1805. [PMID: 34647492 PMCID: PMC8519548 DOI: 10.1080/07853890.2021.1990392] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 09/30/2021] [Indexed: 01/11/2023] Open
Abstract
Coeliac disease (CD), also known as gluten sensitive enteropathy, is an autoimmune intestinal disease induced by gluten in genetically susceptible individuals. Gluten is a common ingredient in daily diet and is one of the main environmental factors to induce coeliac disease. Adhering to gluten free diet (GFD) is an effective method for treating CD. Microbiota plays an extremely important role in maintaining human health, and diet is the main factor to regulate the composition and function of gut microbiota. Recent studies have shown that gluten metabolism is closely related to gastrointestinal tract (GIT) microbiota. With the increasing prevalence of coeliac disease, there is a need for alternative treatments to GFD. In this review, biological medication of gluten, relationship between gluten and gut microflora, effect of GFD on GIT microflora, and effect of probiotics on CD were reviewed. By analysing the research progress on relationship between gluten and gastrointestinal microbiome in coeliac disease, this review tried to explore the prospective and potential mechanism of microecological agents in treating coeliac disease.
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Affiliation(s)
- Xingxing Wu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lin Qian
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Kexin Liu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jing Wu
- Institute of Chinese Medicine, Nanjing Drum Tower Hospital, Nanjing University, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhaowei Shan
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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37
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Sample D, Fouhse J, King S, Huynh HQ, Dieleman LA, Willing BP, Turner J. Baseline Fecal Microbiota in Pediatric Patients With Celiac Disease Is Similar to Controls But Dissimilar After 1 Year on the Gluten-Free Diet. JPGN REPORTS 2021; 2:e127. [PMID: 37206457 PMCID: PMC10191547 DOI: 10.1097/pg9.0000000000000127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 08/02/2021] [Indexed: 05/21/2023]
Abstract
The objectives of this pilot study were to examine fecal microbiota composition of pediatric patients with celiac disease (CD) before and after a 1-year gluten-free diet (GFD) and to determine the association with symptoms and anti-tissue transglutaminase (aTTG) antibody. Methods Stool samples were obtained from pediatric patients with CD and from healthy controls. Patients were classified by the presence (diarrhea, abdominal pain, weight loss) or absence (asymptomatic, headache, fatigue, etc.) of typical CD gastrointestinal symptoms and by aTTG normalization post-GFD intervention (< 7 U/mL). Fecal microbial composition was measured using 16S ribosomal RNA gene amplicon sequencing of the V3-V4 region. Results At diagnosis, 13 of 22 patients with CD had typical gastrointestinal symptoms, the remaining patients having atypical or asymptomatic presentations. After a 1-year GFD, all symptomatic patients improved and 9 of 19 had normalized aTTG. Prior to GFD, no distinct microbial signature was observed between patients and controls (P = 0.39). Post-GFD, patients with CD had a unique microbial signature with reductions in known fiber-degrading bacteria, including Blautia, Dorea, Lactobacillus, and Prevotella compared with controls. Within the patients with CD, microbial composition was not associated with reported symptom presentation or aTTG normalization. Conclusions Pediatric patients with CD only had a unique microbial signature compared with healthy controls when placed on the GFD. These results suggest that pediatric patients with CD may not have a unique fecal microbial signature indicative of inherent dysbiosis, in contrast to that suggested for older patients. In children with CD, diet may play a role in shaping microbial composition more so than disease status.
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Affiliation(s)
- Dory Sample
- From the Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
| | - Janelle Fouhse
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Seema King
- Department of Medicine, Community Health Sciences, University of Calgary, Calgary, AB, Canada
| | - Hien Q. Huynh
- From the Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
| | - Levinus A. Dieleman
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Benjamin P. Willing
- Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada
| | - Justine Turner
- From the Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
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38
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Verdu EF, Schuppan D. Co-factors, Microbes, and Immunogenetics in Celiac Disease to Guide Novel Approaches for Diagnosis and Treatment. Gastroenterology 2021; 161:1395-1411.e4. [PMID: 34416277 DOI: 10.1053/j.gastro.2021.08.016] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 08/10/2021] [Accepted: 08/10/2021] [Indexed: 12/14/2022]
Abstract
Celiac disease (CeD) is a frequent immune-mediated disease that affects not only the small intestine but also many extraintestinal sites. The role of gluten proteins as dietary triggers, HLA-DQ2 or -DQ8 as major necessary genetic predisposition, and tissue transglutaminase (TG2) as mechanistically involved autoantigen, are unique features of CeD. Recent research implicates many cofactors working in synergism with these key triggers, including the intestinal microbiota and their metabolites, nongluten dietary triggers, intestinal barrier defects, novel immune cell phenotypes, and mediators and cytokines. In addition, apart from HLA-DQ2 and -DQ8, multiple and complex predisposing genetic factors and interactions have been defined, most of which overlap with predispositions in other, usually autoimmune, diseases that are linked to CeD. The resultant better understanding of CeD pathogenesis, and its manifold manifestations has already paved the way for novel therapeutic approaches beyond the lifelong strict gluten-free diet, which poses a burden to patients and often does not lead to complete mucosal healing. Thus, supported by improved mouse models for CeD and in vitro organoid cultures, several targeted therapies are in phase 2-3 clinical studies, such as highly effective gluten-degrading oral enzymes, inhibition of TG2, cytokine therapies, induction of tolerance to gluten ingestion, along with adjunctive and preventive approaches using beneficial probiotics and micronutrients. These developments are supported by novel noninvasive markers of CeD severity and activity that may be used as companion diagnostics, allow easy-to perform and reliable monitoring of patients, and finally support personalized therapy for CeD.
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Affiliation(s)
- Elena F Verdu
- Division of Gastroenterology, Department of Internal Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada
| | - Detlef Schuppan
- Institute of Translational Immunology,Research Center for Immune Therapy and Celiac Center, University Medical Center, Johannes Gutenberg University, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
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39
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Comparative Analysis of the Impact of Urolithins on the Composition of the Gut Microbiota in Normal-Diet Fed Rats. Nutrients 2021; 13:nu13113885. [PMID: 34836145 PMCID: PMC8618180 DOI: 10.3390/nu13113885] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 10/25/2021] [Accepted: 10/27/2021] [Indexed: 02/07/2023] Open
Abstract
The gut microbiota consists of a community of microorganisms that inhabit the large intestine. These microbes play important roles in maintaining gut barrier integrity, inflammation, lipid and carbohydrate metabolism, immunity, and protection against pathogens. However, recent studies have shown that dysfunction in the gut microbiota composition can lead to the development of several diseases. Urolithin A has recently been approved as a functional food ingredient. In this study, we examined the potentials of urolithin A (Uro-A) and B (Uro-B) in improving metabolic functions and their impact on gut microbiota composition under a metabolically unchallenged state in normal rats. Male Wistar rats (n = 18) were randomly segregated into three groups, with Group 1 serving as the control group. Groups 2 and 3 were administered with 2.5 mg/kg Uro-A and Uro-B, respectively, for four weeks. Our results showed that both Uro-A and B improved liver and kidney functions without affecting body weight. Metagenomic analysis revealed that both Uro-A and B induced the growth of Akkermansia. However, Uro-A decreased species diversity and microbial richness and negatively impacted the composition of pathogenic microbes in normal rats. Taken together, this study showed the differential impacts of Uro-A and B on the gut microbiota composition in normal rats and would thus serve as a guide in the choice of these metabolites as a functional food ingredient or prebiotic.
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40
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Marzorati M, Van den Abbeele P, Bubeck S, Bayne T, Krishnan K, Young A. Treatment with a spore-based probiotic containing five strains of Bacillus induced changes in the metabolic activity and community composition of the gut microbiota in a SHIME® model of the human gastrointestinal system. Food Res Int 2021; 149:110676. [PMID: 34600678 DOI: 10.1016/j.foodres.2021.110676] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 08/02/2021] [Accepted: 08/26/2021] [Indexed: 12/16/2022]
Abstract
MegaSporeBiotic™ is an oral, spore-based probiotic comprised of five Bacillus spp. (Bacillus indicus HU36, Bacillus subtilis HU58, Bacillus coagulans SC208, Bacillus licheniformis SL307, and Bacillus clausii SC109). The effects of MegaSporeBiotic™ on gut microbiota activity and community composition were evaluated for the first time using an in vitro model of the human gastrointestinal tract, the simulator of the human intestinal microbial ecosystem (SHIME®), under healthy conditions. Following a stabilization period and a control period (2 weeks each), the reactor feed was supplemented with daily MegaSporeBiotic™ for 3 weeks (treatment period). Changes in microbial community activity and composition between the control and treatment periods were evaluated for each colon compartment (ascending [AC], transverse [TC], and descending colon [DC]). Propionate levels increased significantly in the TC (week 2, P = 0.02; week 3, P = 0.0019) and DC (week 2, P = 0.03) with treatment while lactate levels significantly decreased in the TC (week 3, P = 0.03). Ammonium levels were significantly decreased during the final week of treatment (TC, P = 0.02; DC, P = 0.03). Overall, Akkermansia muciniphila, Bifidobacteria spp., and Firmicutes increased with treatment while Lactobacillus spp. and Bacteroidetes decreased. The Firmicutes:Bacteroidetes ratio increased with treatment in the AC compartment. MegaSporeProbiotic™ treatment resulted in changes in metabolism and increased bacterial diversity.
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Affiliation(s)
- Massimo Marzorati
- Center for Microbial Ecology and Technology (CMET), Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium; ProDigest, Technologiepark 82, 9052 Zwijnaarde, Belgium
| | | | - Sarah Bubeck
- Bubeck Scientific Communications, 194 Rainbow Drive #9418, Livingston, TX 77399, USA.
| | - Thomas Bayne
- Microbiome Labs, 101 E Town Pl, Saint Augustine, FL 92092, USA
| | - Kiran Krishnan
- Microbiome Labs, 101 E Town Pl, Saint Augustine, FL 92092, USA
| | - Aicacia Young
- Microbiome Labs, 101 E Town Pl, Saint Augustine, FL 92092, USA
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41
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Rawi M, Abdullah A, Ismail A, Sarbini SR. Manipulation of Gut Microbiota Using Acacia Gum Polysaccharide. ACS OMEGA 2021; 6:17782-17797. [PMID: 34308014 PMCID: PMC8296006 DOI: 10.1021/acsomega.1c00302] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Accepted: 05/19/2021] [Indexed: 05/16/2023]
Abstract
Acacia gum (AG) is a branched-polysaccharide gummy exudate that consists of arabinose and galactose. The traditional practice in African-Middle Eastern countries uses this gum as medicine. Traditional use of AG is to treat stomach disease, which can be a potential functional food. In this research, commercially available AG from Acacia senegal and Acacia seyal was investigated as the prebiotic. The experiment employed a pH-controlled in vitro colon model inoculated with human fecal microbiota to mimic the human colon. Fermentation samples at 0, 6, 12, and 24 h were brought for short-chain fatty acid (SCFA) analysis using high-performance liquid chromatography and bacterial enumeration via fluorescent in situ hybridization. Results showed that AG significantly promotes Bifidobacteria proliferation similar to fructo-oligosaccharides (FOS) while inhibiting the Clostridium histolyticum group, commonly associated with gut dysbiosis. Acetate, propionate, and butyrate showed a similar trend to FOS (p > 0.05). The AG shows potential against gut dysbiosis, as it promotes gut-probiotics, through modulation of microbial population and SCFA production, especially butyrate.
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Affiliation(s)
- Muhamad
Hanif Rawi
- Faculty
of Agricultural Science and Forestry, Universiti
Putra Malaysia Kampus Bintulu Sarawak, Bintulu, Sarawak 97008, Malaysia
| | - Aminah Abdullah
- Faculty
of Science and Technology, Universiti Kebangsaan
Malaysia, Bangi, Selangor 43600, Malaysia
| | - Amin Ismail
- Faculty
of Medicine and Health Sciences, Universiti
Putra Malaysia, Serdang, Selangor 43400, Malaysia
| | - Shahrul Razid Sarbini
- Faculty
of Agricultural Science and Forestry, Universiti
Putra Malaysia Kampus Bintulu Sarawak, Bintulu, Sarawak 97008, Malaysia
- Halal
Products Research Institute, Universiti
Putra Malaysia, Putra
Infoport, Serdang, Selangor 43400 UPM, Malaysia
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42
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Torun A, Hupalowska A, Trzonkowski P, Kierkus J, Pyrzynska B. Intestinal Microbiota in Common Chronic Inflammatory Disorders Affecting Children. Front Immunol 2021; 12:642166. [PMID: 34163468 PMCID: PMC8215716 DOI: 10.3389/fimmu.2021.642166] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 05/24/2021] [Indexed: 12/12/2022] Open
Abstract
The incidence and prevalence rate of chronic inflammatory disorders is on the rise in the pediatric population. Recent research indicates the crucial role of interactions between the altered intestinal microbiome and the immune system in the pathogenesis of several chronic inflammatory disorders in children, such as inflammatory bowel disease (IBD) and autoimmune diseases, such as type 1 diabetes mellitus (T1DM) and celiac disease (CeD). Here, we review recent knowledge concerning the pathogenic mechanisms underlying these disorders, and summarize the facts suggesting that the initiation and progression of IBD, T1DM, and CeD can be partially attributed to disturbances in the patterns of composition and abundance of the gut microbiota. The standard available therapies for chronic inflammatory disorders in children largely aim to treat symptoms. Although constant efforts are being made to maximize the quality of life for children in the long-term, sustained improvements are still difficult to achieve. Additional challenges are the changing physiology associated with growth and development of children, a population that is particularly susceptible to medication-related adverse effects. In this review, we explore new promising therapeutic approaches aimed at modulation of either gut microbiota or the activity of the immune system to induce a long-lasting remission of chronic inflammatory disorders. Recent preclinical studies and clinical trials have evaluated new approaches, for instance the adoptive transfer of immune cells, with genetically engineered regulatory T cells expressing antigen-specific chimeric antigen receptors. These approaches have revolutionized cancer treatments and have the potential for the protection of high-risk children from developing autoimmune diseases and effective management of inflammatory disorders. The review also focuses on the findings of studies that indicate that the responses to a variety of immunotherapies can be enhanced by strategic manipulation of gut microbiota, thus emphasizing on the importance of proper interaction between the gut microbiota and immune system for sustained health benefits and improvement of the quality of life of pediatric patients.
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Affiliation(s)
- Anna Torun
- Chair and Department of Biochemistry, Medical University of Warsaw, Warsaw, Poland
| | - Anna Hupalowska
- Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, United States
| | - Piotr Trzonkowski
- Department of Medical Immunology, Medical University of Gdansk, Gdansk, Poland
| | - Jaroslaw Kierkus
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
| | - Beata Pyrzynska
- Chair and Department of Biochemistry, Medical University of Warsaw, Warsaw, Poland
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43
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Sitkin SI, Avalueva EB, Oreshko LS, Khavkin AI. Intestinal microbiota and dysbiosis in celiac disease. ROSSIYSKIY VESTNIK PERINATOLOGII I PEDIATRII (RUSSIAN BULLETIN OF PERINATOLOGY AND PEDIATRICS) 2021; 66:116-122. [DOI: 10.21508/1027-4065-2021-66-2-116-122] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Affiliation(s)
- S. I. Sitkin
- Mechnikov North-Western State Medical University; Almazov National Medical Research Centre; State Research Institute of Highly Pure Biopreparations
| | | | | | - A. I. Khavkin
- Veltischev Research and Clinical Institute for Pediatrics at the Pirogov Russian National Research Medical University
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Sehrawat N, Yadav M, Singh M, Kumar V, Sharma VR, Sharma AK. Probiotics in microbiome ecological balance providing a therapeutic window against cancer. Semin Cancer Biol 2021; 70:24-36. [PMID: 32574811 DOI: 10.1016/j.semcancer.2020.06.009] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 05/25/2020] [Accepted: 06/11/2020] [Indexed: 02/07/2023]
Abstract
The gut microbiota composition and dietary factors in our food along with the use of prebiotics and probiotics play an important role in the maintenance of human health. A well-balanced gut microbial population is necessary for the host and the microbiota to coexist in a mutually beneficial relationship maintaining homeostasis. Considering the potential of modern technological tools, it is possible nowadays to engineer prebiotic bacteria having a positive influence on the microbiome on one hand while on the other one may have the ease to get rid of the pathogenic proinflammatory microbes or elements causing dysbiosis. Past studies have seen that in cancer there is a loss of inter-microbial relationship cum interactions within microbiota members, the metabolic products produced by them and the host immune system in a microbial ecosystem, leading to dysbiosis. Current review highlights the importance of probiotics in the management of cancer by bringing together majority of the studies together at a single platform and moreover, stresses upon the need to maintain eubiosis in order to evade and inhibit the progression of cancer. Continuous expansion in knowledge about probiotics, their effect on various cancers and the underlying mechanism of action has raised the global scientific interest towards their possible use against different cancers. Furthermore, the article emphasizes upon the need to explore newer therapeutic targets comprising of the microbiome which could further pave the way to the concept of personalized medicines for various kinds of malignancies so as to derive maximum benefits of a treatment modality and to preserve the microbial homeostasis.
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Affiliation(s)
- Nirmala Sehrawat
- Department of Biotechnology, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, 133207, India
| | - Mukesh Yadav
- Department of Biotechnology, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, 133207, India
| | - Manoj Singh
- Department of Biotechnology, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, 133207, India
| | - Vikas Kumar
- Department of Biotechnology, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, 133207, India
| | - Var Ruchi Sharma
- Department of Biotechnology, Sri Guru Gobind Singh College Sector-26, Chandigarh, UT 160019, India
| | - Anil K Sharma
- Department of Biotechnology, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana, 133207, India.
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45
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Sacchetti L, Nardelli C. Gut microbiome investigation in celiac disease: from methods to its pathogenetic role. Clin Chem Lab Med 2021; 58:340-349. [PMID: 31494628 DOI: 10.1515/cclm-2019-0657] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 08/06/2019] [Indexed: 12/12/2022]
Abstract
Our body is inhabited by a variety of microbes (microbiota), mainly bacteria, that outnumber our own cells. Until recently, most of what we knew about the human microbiota was based on culture methods, whereas a large part of the microbiota is uncultivable, and consequently previous information was limited. The advent of culture-independent methods and, particularly, of next-generation sequencing (NGS) methodology, marked a turning point in studies of the microbiota in terms of its composition and of the genes encoded by these microbes (microbiome). The microbiome is influenced predominantly by environmental factors that cause a large inter-individual variability (~20%) being its heritability only 1.9%. The gut microbiome plays a relevant role in human physiology, and its alteration ("dysbiosis") has been linked to a variety of inflammatory gut diseases, including celiac disease (CD). CD is a chronic, immune-mediated disorder that is triggered by both genetic (mainly HLA-DQ2/DQ8 haplotypes) and environmental factors (gluten), but, in recent years, a large body of experimental evidence suggested that the gut microbiome is an additional contributing factor to the pathogenesis of CD. In this review, we summarize the literature that has investigated the gut microbiome associated with CD, the methods and biological samples usually employed in CD microbiome investigations and the putative pathogenetic role of specific microbial alterations in CD. In conclusion, both gluten-microbe and host-microbe interactions drive the gluten-mediated immune response. However, it remains to be established whether the CD-associated dysbiosis is the consequence of the disease, a simple concomitant association or a concurring causative factor.
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Affiliation(s)
- Lucia Sacchetti
- CEINGE-Biotecnologie Avanzate SCarl, Naples, Italy.,Task Force on Microbiome Studies, Università degli Studi di Napoli Federico II and CEINGE-Biotecnologie Avanzate SCarl, Naples, Italy
| | - Carmela Nardelli
- CEINGE-Biotecnologie Avanzate SCarl, Naples, Italy.,Task Force on Microbiome Studies, Università degli Studi di Napoli Federico II and CEINGE-Biotecnologie Avanzate SCarl, Naples, Italy.,Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Naples, Italy
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46
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Contribution of Infectious Agents to the Development of Celiac Disease. Microorganisms 2021; 9:microorganisms9030547. [PMID: 33800833 PMCID: PMC8001938 DOI: 10.3390/microorganisms9030547] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 02/28/2021] [Accepted: 03/02/2021] [Indexed: 02/07/2023] Open
Abstract
The ingestion of wheat gliadin (alcohol-soluble proteins, an integral part of wheat gluten) and related proteins induce, in genetically predisposed individuals, celiac disease (CD), which is characterized by immune-mediated impairment of the small intestinal mucosa. The lifelong omission of gluten and related grain proteins, i.e., a gluten-free diet (GFD), is at present the only therapy for CD. Although a GFD usually reduces CD symptoms, it does not entirely restore the small intestinal mucosa to a fully healthy state. Recently, the participation of microbial components in pathogenetic mechanisms of celiac disease was suggested. The present review provides information on infectious diseases associated with CD and the putative role of infections in CD development. Moreover, the involvement of the microbiota as a factor contributing to pathological changes in the intestine is discussed. Attention is paid to the mechanisms by which microbes and their components affect mucosal immunity, including tolerance to food antigens. Modulation of microbiota composition and function and the potential beneficial effects of probiotics in celiac disease are discussed.
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Poddighe D, Kushugulova A. Salivary Microbiome in Pediatric and Adult Celiac Disease. Front Cell Infect Microbiol 2021; 11:625162. [PMID: 33680992 PMCID: PMC7927425 DOI: 10.3389/fcimb.2021.625162] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 01/06/2021] [Indexed: 12/15/2022] Open
Abstract
The human salivary microbiota includes hundreds of bacterial species. Alterations in gut microbiota have been explored in Celiac Disease (CD), but fewer studies investigated the characteristics of salivary microbiome in these patients, despite the potential implications in its pathogenesis. Indeed, some recent studies suggested that the partial digestion of gluten proteins by some bacteria may affect the array of gluten peptides reaching the gut and the way by which those are presented to the intestinal immune system. The available clinical studies investigating the salivary microbiota in children and adults, are insufficient to make any reliable conclusion, even though some bacterial species/phyla differences have been reported between celiac patients and controls. However, the salivary microbiome could correlate better with the duodenal microbiota, than the fecal one. Therefore, further clinical studies on salivary microbiome by different and independent research groups and including different populations, are advisable in order to explore the usefulness of the salivary microbiome analysis and understand some aspects of CD pathogenesis with potential clinical and practical implications.
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Affiliation(s)
- Dimitri Poddighe
- Department of Medicine, Nazarbayev University School of Medicine (NUSOM), Nur-Sultan, Kazakhstan.,Department of Pediatrics, National Research Center for Mother and Child Health, University Medical Center, Nur-Sultan, Kazakhstan
| | - Almagul Kushugulova
- Laboratory of Human Microbiome and Longevity, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan
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Multidimensional Disadvantages of a Gluten-Free Diet in Celiac Disease: A Narrative Review. Nutrients 2021; 13:nu13020643. [PMID: 33669442 PMCID: PMC7920475 DOI: 10.3390/nu13020643] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/05/2021] [Accepted: 02/09/2021] [Indexed: 12/17/2022] Open
Abstract
A gluten-free diet is the mainstay method of treatment and the prevention of celiac disease complications. However, an inadequately balanced gluten-free diet can increase the risk of obesity, negatively affect glucose and lipid metabolism, and increase the risk of the metabolic syndrome. Therefore, an adequate nutritional counselling is necessary for patients diagnosed with celiac disease in order to prevent and treat the components of the metabolic syndrome.
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Nanoparticles in the Food Industry and Their Impact on Human Gut Microbiome and Diseases. Int J Mol Sci 2021; 22:ijms22041942. [PMID: 33669290 PMCID: PMC7920074 DOI: 10.3390/ijms22041942] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 02/02/2021] [Accepted: 02/10/2021] [Indexed: 12/11/2022] Open
Abstract
The use of inorganic nanoparticles (NPs) has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about how they may impact human health. As the gut microbiome continues to be increasingly implicated in various diseases of unknown etiology, researchers have begun studying the potentially toxic effects of these NPs on the gut microbiome. Unfortunately, conflicting results have limited researcher’s ability to evaluate the true impact of NPs on the gut microbiome in relation to health. This review focuses on the impact of five inorganic NPs (silver, iron oxide, zinc oxide, titanium dioxide, and silicon dioxide) on the gut microbiome and gastrointestinal tract with consideration for various methodological differences within the literature. This is important as NP-induced changes to the gut could lead to various gut-related diseases. These include irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), celiac disease, and colorectal cancer. Research in this area is necessary as the use of NPs in various industries continues to grow along with the number of people suffering from chronic gastrointestinal diseases.
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Shin SY, Hussain Z, Lee YJ, Park H. An altered composition of fecal microbiota, organic acids, and the effect of probiotics in the guinea pig model of postoperative ileus. Neurogastroenterol Motil 2021; 33:e13966. [PMID: 32815235 DOI: 10.1111/nmo.13966] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 06/15/2020] [Accepted: 07/21/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND The aim of this study is to investigate the altered composition of fecal microbiota, organic acids, and the effect of probiotics in the guinea pig model of the postoperative ileus (POI). METHODS A laparotomy with cecal manipulation was performed to induce POI in guinea pigs. Fecal pellets were collected before the operation (the baseline) and 1, 3, and 5 days after the operation. The extracted fecal DNA was amplified and sequenced using the Illumina MiSeq sequencing system. The same POI procedures were performed after oral pretreatment of the probiotics for 7 days before operation. The effect of the probiotics on the selected taxa and fecal acetate were evaluated, as were the butyrate levels. The colonic transit was assessed by measurement of the fecal pellet output. KEY RESULTS The communities of the baseline and POI groups indicated significantly distinct composition. The genera Bifidobacterium and Lactobacillus were more abundant in the baseline group compared with the POI groups, and Bacteroides and Blautia were more abundant in the POI groups. Decreased abundances of the species Bifidobacterium bifidum and Bifidobacterium longum after the POI procedure were significantly increased in the probiotics group. The decreased fecal butyrate level after the POI procedure was significantly increased, and colonic transit was significantly improved in the probiotics group. CONCLUSIONS AND INFERENCES POI induces gut bacterial dysbiosis. Moreover, pretreatment of probiotics before operation restores the beneficial bacterial species, butyrate production, and bowel movement. The modulation of gut microbiota may help the treatment and prevention of POI.
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Affiliation(s)
- Seung Yong Shin
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Zahid Hussain
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Ju Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyojin Park
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
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