DOCSLIB.ORG

Akkermansia Muciniphila

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Akkermansia Muciniphila Intestinal Immunity to the Commensal Bacterium Akkermansia muciniphila By Eduardo Ansaldo Gine A dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Molecular and Cell Biology in the Graduate Division of the University of California, Berkeley Committee in charge: Professor Gregory Barton, Chair Professor Ellen Robey Professor Sarah Stanley Professor Michael Shapira Summer 2019 Abstract Intestinal Immunity to the Commensal Bacterium Akkermansia muciniphila By Eduardo Ansaldo Gine Doctor of Philosophy in Molecular and Cell Biology University of California, Berkeley Professor Gregory Barton, Chair Intestinal immunity plays critical roles in maintaining host health. Despite the abundance of foreign antigens and activated lymphocytes in the intestine, only a few commensal bacteria that induce cognate adaptive immune responses during homeostasis have been identified. In this dissertation, I reveal that Akkermansia muciniphila, an intestinal bacterium associated with beneficial effects on host metabolism and cancer immunotherapy, induces cognate T-dependent immunoglobulin G1 (IgG1) and IgA antibody responses and antigen-specific T cell responses during homeostasis. In contrast to the select few examples of previously characterized mucosal responses to commensal bacteria, T cell responses to A. muciniphila are limited to T follicular helper cells in the Peyer’s patches in a gnotobiotic setting, without appreciable induction of other T helper fates or migration to the lamina propria. However, A. muciniphila-specific responses are context-dependent, and adopt other T helper fates in the setting of a conventional microbiota. These findings suggest that contextual signals influence T cell immunity to the microbiota and modulate host immune function during homeostasis. Interestingly, T cells specific to A. muciniphila expand dramatically in a novel (but still uncharacterized) genetic mouse model of intestinal inflammation, suggesting that this bacterium may become a major mucosal antigen when homeostasis is disrupted. If so, T cell immunity to A. muciniphila may play critical roles during infection and inflammatory bowel diseases. 1 This dissertation is dedicated to my mother, whose unrealized dream was to become a scientist, and to my father, who always supported me in pursuing my own interests. i Table of Contents Chapter 1: Immunity and the microbiota ...................................................................... 1 From model antigens to commensal bacteria .......................................................................................... 1 The immune system and the microbiota in the intestine ......................................................................... 2 B cell responses to the microbiota in the intestine .................................................................................. 4 T cell responses to the microbiota in the intestine ................................................................................... 5 Chapter 2: Commensal bacteria induce T-dependent IgG antibody responses during homeostasis ....................................................................................................... 9 Background: ............................................................................................................................................ 9 Results: .................................................................................................................................................. 11 Discussion: ............................................................................................................................................ 13 Methods: ................................................................................................................................................ 14 Figures: .................................................................................................................................................. 16 Chapter 3: A. muciniphila induces cognate IgG1 antibody responses in conventional and gnotobiotic mice ............................................................................ 21 Background: .......................................................................................................................................... 21 Results: .................................................................................................................................................. 23 Discussion: ............................................................................................................................................ 25 Methods: ................................................................................................................................................ 27 Figures: .................................................................................................................................................. 29 Chapter 4: A. muciniphila induces antigen-specific T cell responses during homeostasis.................................................................................................................. 33 Background: .......................................................................................................................................... 33 Results: .................................................................................................................................................. 35 Discussion: ............................................................................................................................................ 38 Methods: ................................................................................................................................................ 39 Figures: .................................................................................................................................................. 44 Chapter 5: Description of a novel mouse line that induces ectopic responses to the microbiota ............................................................................................................... 57 Background: .......................................................................................................................................... 57 Results: .................................................................................................................................................. 58 Discussion: ............................................................................................................................................ 62 Methods: ................................................................................................................................................ 64 Figures: .................................................................................................................................................. 66 Chapter 6: Concluding remarks .................................................................................. 74 References: ................................................................................................................... 77 ii List of Figures Figure 2.1. Mice generate anti-commensal IgG1 antibodies during homeostasis ....................... 16 Figure 2.2. Anti-commensal IgG1 antibodies, but not other isotypes, are T cell-dependent ....... 18 Figure 2.3. Supporting data for sorting and 16S rDNA sequencing of IgG1-bound and unbound bacteria ......................................................................................................................................... 19 Figure 2.4. Additional IgG1-Seq experiments confirm targeting of Akkermansia and Bacteroides S24-7 ............................................................................................................................................. 20 Figure 3.1 Akkermansia muciniphila is necessary and sufficient to induce cognate A. muciniphila-specific IgG1 antibody responses ............................................................................. 29 Figure 3.2 A. muciniphila induces antigen-specific IgG1 and IgA antibody responses in SPF and gnotobiotic mice ........................................................................................................................... 31 Figure 4.1. Generation of A. muciniphila-specific hybridomas, TCR transgenic mice, and I-Ab tetramers ...................................................................................................................................... 45 Figure 4.2. Generation of A. muciniphila-specific I-Ab tetramers and validation of T cell lines ... 46 Figure 4.3 Characterization of Amuc124 TCR Transgenic mice .................................................... 48 Figure 4.4. A. muciniphila induces antigen-specific T follicular helper cell responses during homeostasis .................................................................................................................................. 50 Figure 4.5. Amuc124 TCR transgenic Rag1+/+ and Rag1–/– cells expand similarly in ASF+Akk mice ...................................................................................................................................................... 51 Figure 4.6. Endogenous A. muciniphila-specific T cells localize to the Peyer’s patches and adopt TFH markers. .................................................................................................................................. 52 Figure 4.7. A. muciniphila-specific
Load more

Recommended publications
  • Gastrointestinal Status and Microbiota Shaping in Amyotrophic Lateral Sclerosis: a New Frontier for Targeting?
    8 Gastrointestinal Status and Microbiota Shaping in Amyotrophic Lateral Sclerosis: A New Frontier for Targeting? Letizia Mazzini1 • Fabiola De Marchi1 • Elena Niccolai2 • Jessica Mandrioli3, Amedeo Amedei2 1ALS Centre, Department of Neurology, Maggiore della Carità Hospital, University of Piemonte Orientale, Novara, Italy; 2Department of Experimental and clinical Medicine, University of Florence, Firenze, Italy; 3Department of Biomedical, Metabolic and Neural Science, University of Modena and Reggio Emilia, Modena, Italy Author for correspondence: Letizia Mazzini, ALS Centre, Department of Neurology, Maggiore della Carità Hospital, University of Piemonte Orientale, Novara, Italy. Email: [email protected] Doi: https://doi.org/10.36255/exonpublications.amyotrophiclateralsclerosis. microbiota.2021 Abstract: Amyotrophic lateral sclerosis (ALS) is a rare and severe neurodegenera- tive disease affecting the upper and lower motor neurons, causing diffuse muscle paralysis. Etiology and pathogenesis remain largely unclear, but several environ- mental, genetic, and molecular factors are thought to be involved in the disease process. Emerging data identify a relationship between gut microbiota dysbiosis and neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, and ALS. In these disorders, neuroinflammation is being increasingly recognized as a driver for disease onset and progression. Gut bacteria play a crucial role in In: Amyotrophic Lateral Sclerosis. Araki T (Editor), Exon Publications, Brisbane, Australia. ISBN:
    [Show full text]
  • Diversity in the Extracellular Vesicle-Derived Microbiome of Tissues According to Tumor Progression in Pancreatic Cancer
    cancers Article Diversity in the Extracellular Vesicle-Derived Microbiome of Tissues According to Tumor Progression in Pancreatic Cancer Jin-Yong Jeong 1, Tae-Bum Kim 2 , Jinju Kim 1, Hwi Wan Choi 1, Eo Jin Kim 1, Hyun Ju Yoo 1 , Song Lee 3, Hye Ryeong Jun 3, Wonbeak Yoo 4 , Seokho Kim 5, Song Cheol Kim 3,6,* and Eunsung Jun 1,3,* 1 Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine and Asan Medical Center, Seoul 05505, Korea; [email protected] (J.-Y.J.); [email protected] (J.K.); [email protected] (H.W.C.); [email protected] (E.J.K.); [email protected] (H.J.Y.) 2 Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; [email protected] 3 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; [email protected] (S.L.); [email protected] (H.R.J.) 4 Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Korea; [email protected] 5 Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan 49315, Korea; [email protected] 6 Biomedical Engineering Research Center, Asan Institute of Life Science, AMIST, Asan Medical Center, Seoul 05505, Korea * Correspondence: [email protected] (S.C.K.); [email protected] (E.J.); Tel.: +82-2-3010-3936 (S.C.K.); +82-2-3010-1696 (E.J.); Fax: +82-2-474-9027 (S.C.K.); +82-2-474-9027 (E.J.) Received: 13 July 2020; Accepted: 17 August 2020; Published: 19 August 2020 Abstract: This study was conducted to identify the composition and diversity of the microbiome in tissues of pancreatic cancer and to determine its role.
    [Show full text]
  • Akkermansia Muciniphila Ameliorates the Age-Related Decline in Colonic
    van der Lugt et al. Immunity & Ageing (2019) 16:6 https://doi.org/10.1186/s12979-019-0145-z RESEARCH Open Access Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1−/Δ7 mice Benthe van der Lugt1*†, Adriaan A. van Beek2,3†, Steven Aalvink4, Ben Meijer3, Bruno Sovran5, Wilbert P. Vermeij6,7, Renata M. C. Brandt6, Willem M. de Vos4,8, Huub F. J. Savelkoul3, Wilma T. Steegenga1 and Clara Belzer4* Abstract Background: The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1−/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. Results: The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected.
    [Show full text]
  • Toxicological Safety Evaluation of Pasteurized Akkermansia Muciniphila
    Received: 6 July 2020 Revised: 10 July 2020 Accepted: 10 July 2020 DOI: 10.1002/jat.4044 RESEARCH ARTICLE Toxicological safety evaluation of pasteurized Akkermansia muciniphila Céline Druart1 | Hubert Plovier1 | Matthias Van Hul2 | Alizée Brient3 | Kirt R. Phipps4 | Willem M. de Vos5,6 | Patrice D. Cani2 1A-Mansia Biotech SA, Mont-Saint-Guibert, Belgium Abstract 2Walloon Excellence in Life Sciences and Gut microorganisms are vital for many aspects of human health, and the commensal BIOtechnology (WELBIO), Metabolism and bacterium Akkermansia muciniphila has repeatedly been identified as a key compo- Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université nent of intestinal microbiota. Reductions in A. muciniphila abundance are associated catholique de Louvain, Brussels, Belgium with increased prevalence of metabolic disorders such as obesity and type 2 diabetes. 3Citoxlab France, Evreux, France It was recently discovered that administration of A. muciniphila has beneficial effects 4Intertek Health Sciences Inc., Farnborough, Hampshire, UK and that these are not diminished, but rather enhanced after pasteurization. Pasteur- 5Laboratory of Microbiology, Wageningen ized A. muciniphila is proposed for use as a food ingredient, and was therefore sub- University, Wageningen, the Netherlands jected to a nonclinical safety assessment, comprising genotoxicity assays (bacterial 6Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, reverse mutation and in vitro mammalian cell micronucleus tests) and a 90-day toxic- Helsinki, Finland ity study. For the latter, Han Wistar rats were administered with the vehicle or pas- Correspondence teurized A. muciniphila at doses of 75, 375 or 1500 mg/kg body weight/day Patrice D. Cani, UCLouvain, Université (equivalent to 4.8 × 109, 2.4 × 1010, or 9.6 × 1010 A.
    [Show full text]
  • Experimental Evaluation of Ecological Principles to Understand and Modulate the Outcome of Bacterial Strain Competition in Gut Microbiomes
    Experimental evaluation of ecological principles to understand and modulate the outcome of bacterial strain competition in gut microbiomes Rafael R. Segura Munoz University of Nebraska-Lincoln Sara Mantz University of Nebraska-Lincoln Ines Martinez University of Alberta Robert J. Schmaltz University of Nebraska-Lincoln Jens Walter ( [email protected] ) APC Microbiome Ireland; University College Cork Amanda E. Ramer-Tait ( [email protected] ) University of Nebraska-Lincoln Research Article Keywords: Microbiome, niche, competitive exclusion, coexistence theory, gut ecosystems, engraftment, live biotherapeutics, intraspecic interactions, priority effects Posted Date: December 8th, 2020 DOI: https://doi.org/10.21203/rs.3.rs-123088/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/33 Abstract It is unclear if coexistence theory can be applied to gut microbiomes to understand their characteristics and modulate their composition. Through strictly controlled colonization experiments in mice, we demonstrated that strains of Akkermansia muciniphila and Bacteroides vulgatus could only be established if microbiomes were devoid of exactly these species. Strains of A. muciniphila showed strict competitive exclusion, while B. vulgates strains coexistedbut populations were still inuenced by competitive interactions. Priority effects were detected for both species as strains’ competitive tness increased when colonizing rst. Based on these observations, we devised a subtractive strategy for A. muciniphila using antibiotics and demonstrated that a strain from an assembled community can be stably replaced by another strain. Altogether, these results suggest that aspects of coexistence theory, e.g., niche partitioning and the impact of priority effects on tness differences, can be applied to explain ecological characteristics of gut microbiomes and modulate their composition.
    [Show full text]
  • Akkermansia Muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer Downloaded From
    Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer Downloaded from Justus Reunanen,a Veera Kainulainen,a Laura Huuskonen,a Noora Ottman,b Clara Belzer,b Heikki Huhtinen,c Willem M. de Vos,a,b,d Reetta Satokaria,e Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finlanda; Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlandsb; Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finlandc; Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finlandd; Functional Foods Forum, University of Turku, Turku, Finlande http://aem.asm.org/ Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. A. muciniphila has been linked with intestinal health and improved metabolic status in obese and type 2 diabetic subjects. Specifically, A. muciniphila has been shown to reduce high-fat-diet-induced endotoxemia, which develops as a result of an impaired gut barrier. Despite the accumulating evidence of the health-promoting effects of A. muciniphila, the mechanisms of interaction of the bacterium with the host have received little attention. In this study, we used several in vitro models to inves- tigate the adhesion of A. muciniphila to the intestinal epithelium and its interaction with the host mucosa. We found that A. muciniphila adheres strongly to the Caco-2 and HT-29 human colonic cell lines but not to human colonic mucus. In addition, A. muciniphila showed binding to the extracellular matrix protein laminin but not to collagen I or IV, fibronectin, or fetuin. Im- on March 20, 2018 by TERKKO NATIONAL LIBRARY OF HEALTH SCIENCES portantly, A.
    [Show full text]
  • Akkermansia Muciniphila for Its Future Application Paranymphs Steven Aalvink E a P L I C [email protected]
    M e t a b Invitation o l i c c h You are kindly invited to a r a attend the public defense c t e of my PhD thesis r i z a t i o n a Metabolic n d v characterization i a b l e and viable delivery of d e l Akkermansia i v e r y muciniphila o f A for its future application k k e r m Monday, January 22, 2018 a n at 4 pm in the Aula of s i a Wageningen University m Generaal Foulkesweg 1A, u c Metabolic characterization Wageningen i n i p h and viable delivery of i Kees C. H. van der Ark l a f [email protected] o r Akkermansia muciniphila i t s f u Paranymphs t for its future application u r Steven Aalvink e a [email protected] p p l i c a Hugo de Vries t i o [email protected] n 2 0 Kees C. H. van der Ark 1 8 Metabolic characterization and viable delivery of Akkermansia muciniphila for its future application Kees C.H. van der Ark Metabolic characterization and viable delivery of Akkermansia muciniphila for its future application Kees C.H. van der Ark Thesis committee Promotor Prof. Dr Willem M. de Vos Professor of Microbiology Wageningen University & Research Thesis Co-promotor Dr Clara Belzer submitted in fulfilment of the requirements for the degree of doctor Assistant professor, Laboratory of Microbiology at Wageningen University Wageningen University & Research by the authority of the Rector Magnificus, Other members Prof.
    [Show full text]
  • The Impact of Microbiota on the Pathogenesis of Amyotrophic Lateral Sclerosis and the Possible Benefits of Polyphenols
    H OH metabolites OH Review The Impact of Microbiota on the Pathogenesis of Amyotrophic Lateral Sclerosis and the Possible Benefits of Polyphenols. An Overview Julia Casani-Cubel 1 , María Benlloch 2,* , Claudia Emmanuela Sanchis-Sanchis 2,* , Raquel Marin 3 , Jose María Lajara-Romance 4 and Jose Enrique de la Rubia Orti 2 1 Doctoral Degree School, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain; [email protected] 2 Department of Health Science, Catholic University San Vicente Mártir, 46001 Valencia, Spain; [email protected] 3 Laboratory of Cellular Neurobiology, School of Medicine, Faculty of Health Sciences, University of La Laguna, 38190 Tenerife, Spain; [email protected] 4 Multimedia Department, Catholic University of Valencia San Vicente Mártir, 46001 Valencia, Spain; [email protected] * Correspondence: [email protected] (M.B.); [email protected] (C.E.S.-S.) Abstract: The relationship between gut microbiota and neurodegenerative diseases is becoming clearer. Among said diseases amyotrophic lateral sclerosis (ALS) stands out due to its severity and, as with other chronic pathologies that cause neurodegeneration, gut microbiota could play a fundamental role in its pathogenesis. Therefore, polyphenols could be a therapeutic alternative due Citation: Casani-Cubel, J.; Benlloch, to their anti-inflammatory action and probiotic effect. Thus, the objective of our narrative review M.; Sanchis-Sanchis, C.E.; Marin, R.; was to identify those bacteria that could have connection with the mentioned disease (ALS) and to Lajara-Romance, J.M.; de la Rubia analyze the benefits produced by administering polyphenols. Therefore, an extensive search was Orti, J.E. The Impact of Microbiota on carried out selecting the most relevant articles published between 2005 and 2020 on the PubMed and the Pathogenesis of Amyotrophic EBSCO database on research carried out on cell, animal and human models of the disease.
    [Show full text]
  • Genome Sequencing of 39 Akkermansia Muciniphila Isolates Reveals Its Population Structure, Genomic and Functional Diverisity, An
    Guo et al. BMC Genomics (2017) 18:800 DOI 10.1186/s12864-017-4195-3 RESEARCHARTICLE Open Access Genome sequencing of 39 Akkermansia muciniphila isolates reveals its population structure, genomic and functional diverisity, and global distribution in mammalian gut microbiotas Xianfeng Guo1†, Shenghui Li2†, Jiachun Zhang1, Feifan Wu1, Xiangchun Li2, Dan Wu1, Min Zhang1, Zihao Ou1, Zhuye Jie2, Qiulong Yan3, Peng Li2, Jiangfeng Yi4 and Yongzheng Peng1* Abstract Background: Akkermansia muciniphila is one of the most dominant bacteria that resides on the mucus layer of intestinal tract and plays key role in human health, however, little is known about its genomic content. Results: Herein, we for the first time characterized the genomic architecture of A. muciniphila based on whole-genome sequencing, assembling, and annotating of 39 isolates derived from human and mouse feces. We revealed a flexible open pangenome of A. muciniphila currently consisting of 5644 unique proteins. Phylogenetic analysis identified three species-level A. muciniphila phylogroups exhibiting distinct metabolic and functional features. Based on the comprehensive genome catalogue, we reconstructed 106 newly A. muciniphila metagenome assembled genomes (MAGs) from available metagenomic datasets of human, mouse and pig gut microbiomes, revealing a transcontinental distribution of A. muciniphila phylogroups across mammalian gut microbiotas. Accurate quantitative analysis of A. muciniphila phylogroups in human subjects further demonstrated its strong correlation with body mass index and anti-diabetic drug usage. Furthermore, we found that, during their mammalian gut evolution history, A. muciniphila acquired extra genes, especially antibiotic resistance genes, from symbiotic microbes via recent lateral gene transfer. Conclusions: The genome repertoire of A. muciniphila provided insights into population structure, evolutionary and functional specificity of this significant bacterium.
    [Show full text]
  • Schistosoma Mansoni Infection Is Associated with Quantitative and Qualitative Modifications of the Mammalian Intestinal Microbio
    www.nature.com/scientificreports OPEN Schistosoma mansoni infection is associated with quantitative and qualitative modifcations of the Received: 4 April 2018 Accepted: 20 July 2018 mammalian intestinal microbiota Published: xx xx xxxx Timothy P. Jenkins1, Laura E. Peachey1, Nadim J. Ajami 2, Andrew S. MacDonald 3, Michael H. Hsieh4,5,6, Paul J. Brindley7, Cinzia Cantacessi 1 & Gabriel Rinaldi7,8 In spite of the extensive contribution of intestinal pathology to the pathophysiology of schistosomiasis, little is known of the impact of schistosome infection on the composition of the gut microbiota of its mammalian host. Here, we characterised the fuctuations in the composition of the gut microbial fora of the small and large intestine, as well as the changes in abundance of individual microbial species, of mice experimentally infected with Schistosoma mansoni with the goal of identifying microbial taxa with potential roles in the pathophysiology of infection and disease. Bioinformatic analyses of bacterial 16S rRNA gene data revealed an overall reduction in gut microbial alpha diversity, alongside a signifcant increase in microbial beta diversity characterised by expanded populations of Akkermansia muciniphila (phylum Verrucomicrobia) and lactobacilli, in the gut microbiota of S. mansoni-infected mice when compared to uninfected control animals. These data support a role of the mammalian gut microbiota in the pathogenesis of hepato-intestinal schistosomiasis and serves as a foundation for the design of mechanistic studies to unravel the complex relationships amongst parasitic helminths, gut microbiota, pathophysiology of infection and host immunity. Schistosomiasis, a major neglected tropical disease, is considered the most problematic of the human helmin- thiases in terms of morbidity and mortality1.
    [Show full text]
  • Akkermansia Muciniphila: Key Player in Metabolic and Gastrointestinal Disorders
    European Review for Medical and Pharmacological Sciences 2019; 23: 8075-8083 Akkermansia muciniphila: key player in metabolic and gastrointestinal disorders I.G. MACCHIONE1,2, L.R. LOPETUSO1,2, G. IANIRO1,2, M. NAPOLI1,2, G. GIBIINO1,2, G. RIZZATTI1,2, V. PETITO1, A. GASBARRINI1,2, F. SCALDAFERRI1,2 1Istituto di Patologia Speciale Medica, Università Cattolica del Sacro Cuore, Rome, Italy 2UOC Medicina Interna e Gastroenterologia, Area Medicina Interna, Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy Abstract. – OBJECTIVE: Gut microbiota has as the “gut microbiota”, has been estimated to a key role in host metabolic regulation and im- exceed 1014 microorganisms, which encompasses mune response, and its dysbiosis represents ~10 times more bacterial cells than the number one of the main causes of gastrointestinal dis- of human cells and over 100 times the amount eases. In this scenario, Akkermansia muciniph- of genomic content (microbiome) as the human ila is a crucial player in keeping the integrity of 1,2 the gastrointestinal tract. genome . MATERIALS AND METHODS: This review fo- Latest evidence supports the role of gut micro- cuses on the correlation between gut microbio- biota in several host functions, and this dysbiotic ta and intestinal homeostasis, primarily explor- condition has been linked to cardiovascular dis- ing A. muciniphila and its involvement in the de- ease, neurodegenerative conditions, psychiatric velopment of metabolic disorders and gastroin- disorders, and autoimmune conditions3-6. testinal diseases. 7,8 RESULTS: Akkermansia muciniphila belongs to Early studies sought to identify the normal the Verrucomicrobia phylum, and it colonizes the set of microbes that colonizes healthy people, mucus layer in the gastrointestinal tract, repre- by culture and characterization of physiological senting 1 to 4% of the fecal microbiota.
    [Show full text]
  • Download from NCBI at Dec
    bioRxiv preprint doi: https://doi.org/10.1101/2020.09.10.292292; this version posted September 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 A thousand metagenome-assembled genomes of Akkermansia reveal new 2 phylogroups and geographical and functional variations in human gut 3 4 Qing-Bo Lv 1, 2, Sheng-Hui Li 3, Yue Zhang 3, Yan-Chun Wang 4, Yong-Zheng Peng 5, #, 5 Xiao-Xuan Zhang 1, # 6 7 1. College of Veterinary Medicine, Qingdao Agricultural University, Qingdao 266109, China. 8 2. College of Animal Science & Veterinary Medicine, Heilongjiang Bayi Agricultural 9 University, Daqing 163319, China. 10 3. Shenzhen Puensum Genetech Institute, Shenzhen 518052, China. 11 4. College of Animal Science and Technology, Jilin Agricultural University, Changchun 12 130118, China 13 5. Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, 14 Guangzhou 510282, China. 15 16 17 #Address correspondence to Y.Z.P. ([email protected]) and X.X.Z. 18 ([email protected]) 19 20 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.09.10.292292; this version posted September 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 21 Abstract 22 The present study revealed the genomic architecture of Akkermansia in human gut by 23 analyzing 1,119 near-complete metagenome-assembled genomes, 84 public available 24 genomes, and 1 newly sequenced A. glycaniphila strain.
    [Show full text]