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      Gut Microbiota: The Missing Link Between Helicobacter pylori Infection and Metabolic Disorders?

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          Abstract

          Helicobacter pylori ( H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. Although the majority of infected individuals remain asymptomatic, this bacterium colonizes the gastric mucosa causing the development of various clinical conditions as peptic ulcers, chronic gastritis and gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas, but complications are not limited to gastric ones. Extradigestive pathologies, including metabolic disturbances such as diabetes, obesity and nonalcoholic fatty liver disease, have also been associated with H. pylori infection. However, the underlying mechanisms connecting H. pylori with extragastric metabolic diseases needs to be clarified. Notably, the latest studies on the topic have confirmed that H. pylori infection modulates gut microbiota in humans. Damage in the gut bacterial community (dysbiosis) has been widely related to metabolic dysregulation by affecting adiposity, host energy balance, carbohydrate metabolism, and hormonal modulation, among others. Taking into account that Type 2 diabetic patients are more prone to be H. pylori positive, gut microbiota emerges as putative key factor responsible for this interaction. In this regard, the therapy of choice for H. pylori eradication, based on proton pump inhibitor combined with two or more antibiotics, also alters gut microbiota composition, but consequences on metabolic health of the patients has been scarcely explored. Recent studies from our group showed that, despite decreasing gut bacterial diversity, conventional H. pylori eradication therapy is related to positive changes in glucose and lipid profiles. The mechanistic insights explaining these effects should also be addressed in future research. This review will deal with the role of gut microbiota as the linking factor between H. pylori infection and metabolic diseases, and discussed the impact that gut bacterial modulation by H. pylori eradication treatment can also have in host’s metabolism. For this purpose, new evidence from the latest human studies published in more recent years will be analyzed.

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          An obesity-associated gut microbiome with increased capacity for energy harvest.

          The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
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            A metagenome-wide association study of gut microbiota in type 2 diabetes.

            Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.
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              Microbial ecology: human gut microbes associated with obesity.

              Two groups of beneficial bacteria are dominant in the human gut, the Bacteroidetes and the Firmicutes. Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Our findings indicate that obesity has a microbial component, which might have potential therapeutic implications.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/931505
                URI : https://loop.frontiersin.org/people/549627
                URI : https://loop.frontiersin.org/people/650164
                URI : https://loop.frontiersin.org/people/711845
                Journal
                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                1664-2392
                17 June 2021
                2021
                : 12
                : 639856
                Affiliations
                [1] 1 Unidad de Gestión Clínica de Endocrinología y Nutrición (Hospital Universitario Virgen de la Victoria), Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga , Málaga, Spain
                [2] 2 Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII) , Madrid, Spain
                [3] 3 Department of Cell Biology, Physiology and Immunology. Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)-Reina Sofia University Hospital, University of Cordoba , Córdoba, Spain
                Author notes

                Edited by: Hamid El Azzouzi, Erasmus Medical Center, Netherlands

                Reviewed by: Ma. Cecilia Opazo, Andres Bello University, Chile; Antonio Salgado Somoza, Independent Researcher, Neufchateau, Belgium

                *Correspondence: Francisco J. Tinahones, fjtinahones@ 123456uma.es ; Mercedes Clemente-Postigo, mer.cp@ 123456hotmail.com

                †These authors have contributed equally to this work and share first authorship

                ‡These authors have contributed equally to this work and share last authorship

                This article was submitted to Translational Endocrinology, a section of the journal Frontiers in Endocrinology

                Article
                10.3389/fendo.2021.639856
                8247771
                34220702
                bada0ea5-a931-4681-8bde-2ca67812131b
                Copyright © 2021 Martin-Nuñez, Cornejo-Pareja, Clemente-Postigo and Tinahones

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 December 2020
                : 17 May 2021
                Page count
                Figures: 0, Tables: 3, Equations: 0, References: 192, Pages: 19, Words: 10866
                Funding
                Funded by: Ministerio de Ciencia, Innovación y Universidades 10.13039/100014440
                Award ID: Juan de la Cierva Formación FJCI-2017-34349, Juan de la Cierva Formación FJCI-2017-32194
                Funded by: Instituto de Salud Carlos III 10.13039/501100004587
                Award ID: Juan Rodés JR19/00054, Río Hortega CM 17/00169, PI18/01160
                Funded by: Consejería de Salud y Familias, Junta de Andalucía 10.13039/501100010566
                Award ID: PI-0092-2017 , RIC-0539-2018
                Funded by: European Regional Development Fund 10.13039/501100008530
                Categories
                Endocrinology
                Review

                Endocrinology & Diabetes
                helicobacter pylori,gut microbiota,metabolism,eradication therapy for helicobacter pylori,metabolic diseases,diabetes

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