|
1
|
Heidrich V, Valles-Colomer M, Segata N. Human microbiome acquisition and transmission. Nat Rev Microbiol 2025:10.1038/s41579-025-01166-x. [PMID: 40119155 DOI: 10.1038/s41579-025-01166-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/14/2025] [Indexed: 03/24/2025]
Abstract
As humans, we host personal microbiomes intricately connected to our biology and health. Far from being isolated entities, our microbiomes are dynamically shaped by microbial exchange with the surroundings, in lifelong microbiome acquisition and transmission processes. In this Review, we explore recent studies on how our microbiomes are transmitted, beginning at birth and during interactions with other humans and the environment. We also describe the key methodological aspects of transmission inference, based on the uniqueness of the building blocks of the microbiome - single microbial strains. A better understanding of human microbiome transmission will have implications for studies of microbial host regulation, of microbiome-associated diseases, and for effective microbiome-targeting strategies. Besides exchanging strains with other humans, there is also preliminary evidence we acquire microorganisms from animals and food, and thus a complete understanding of microbiome acquisition and transmission can only be attained by adopting a One Health perspective.
Collapse
Affiliation(s)
| | | | - Nicola Segata
- Department CIBIO, University of Trento, Trento, Italy.
- Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy.
- Department of Twins Research and Genetic Epidemiology, King's College London, London, UK.
| |
Collapse
|
|
2
|
Moyo GT, Tepekule B, Katsidzira L, Blaser MJ, Metcalf CJE. Getting ahead of human-associated microbial decline in Africa: the urgency of sampling in light of epidemiological transition. Trends Microbiol 2025:S0966-842X(25)00005-8. [PMID: 40021386 DOI: 10.1016/j.tim.2025.01.004] [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: 09/15/2024] [Revised: 01/03/2025] [Accepted: 01/14/2025] [Indexed: 03/03/2025]
Abstract
Evidence is growing that human-associated early-life microbial diversity modulates health over the long term, via effects in the infant termed 'immune and metabolic education'. Documenting high microbial diversity contexts, such as in Africa, thus, has rich potential for understanding this aspect of the landscape of health. Yet, change on the continent is occurring rapidly, and microbial communities are shifting as behaviors and diets are altered, and antibiotic use expands; we may be losing the opportunity to obtain relevant data. After introducing what is known about the effects of early life microbial diversity on late life health, we provide an overview of what is known of the current, and expected future, trajectory of human-associated microbial diversity in Africa, introducing data on the core drivers. We argue that critical insights may be lost if better understanding of infant microbial communities in Africa is not obtained soon.
Collapse
Affiliation(s)
- Gugulethu T Moyo
- Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
| | - Burcu Tepekule
- Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA
| | - Leolin Katsidzira
- Department of Internal Medicine, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe
| | - Martin J Blaser
- Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ, USA
| | - C Jessica E Metcalf
- Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA
| |
Collapse
|
|
3
|
Schweitzer M, Wassermann B, Abdelfattah A, Cernava T, Berg G. Microbiome Literacy: Enhancing Public and Academic Understanding Through the 'Microbiome & Health' Online Course. Microb Biotechnol 2025; 18:e70094. [PMID: 39936816 DOI: 10.1111/1751-7915.70094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 01/07/2025] [Accepted: 01/10/2025] [Indexed: 02/13/2025] Open
Abstract
Microorganisms are fundamental to life on Earth, influencing biogeochemical processes, soil fertility, and the health of humans, animals and plants. Human activities have left a remarkable footprint on the environment, including global microbiomes. Enhancing awareness and improving education about microbiome functions can contribute to a sustainable economy and resilient systems. However, public understanding of microbiome science is hindered by misinformation and limited accessible educational resources. To address this, we developed the massive open online course (MOOC) 'Microbiome & Health', available on iMooX.at and YouTube. The course, structured into six units, covers microbiome concepts, methodologies, human and plant microbiomes, antibiotic resistance, and environmental impacts, aligning with the One Health concept and the Sustainable Development Goals of the United Nations. Initial results show that the MOOC provides the means to increase microbiology literacy, with 73.2% external participation and above-average completion rates. Integration as a mandatory component in university courses has improved student performance, halting declining grades and pass rates. This highlights the MOOC's potential to enhance public and academic understanding of microbiome science, fostering informed decisions for sustainable health and environmental stewardship as well as paving the way for new microbiome-based solutions in biotechnology.
Collapse
Affiliation(s)
- Matthias Schweitzer
- Institute of Environmental Biotechnology, Graz University of Technology, Graz, Austria
| | - Birgit Wassermann
- Institute of Environmental Biotechnology, Graz University of Technology, Graz, Austria
| | - Ahmed Abdelfattah
- Institute of Environmental Biotechnology, Graz University of Technology, Graz, Austria
- Leibniz Institute for Agricultural Engineering and Bioeconomy (ATB), Potsdam, Germany
- Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany
| | - Tomislav Cernava
- Institute of Environmental Biotechnology, Graz University of Technology, Graz, Austria
- School of Biological Sciences, Faculty of Environmental and Life Sciences, Southampton, UK
| | - Gabriele Berg
- Institute of Environmental Biotechnology, Graz University of Technology, Graz, Austria
- Leibniz Institute for Agricultural Engineering and Bioeconomy (ATB), Potsdam, Germany
- Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany
| |
Collapse
|
|
4
|
Beghini F, Pullman J, Alexander M, Shridhar SV, Prinster D, Singh A, Matute Juárez R, Airoldi EM, Brito IL, Christakis NA. Gut microbiome strain-sharing within isolated village social networks. Nature 2025; 637:167-175. [PMID: 39567691 PMCID: PMC11666459 DOI: 10.1038/s41586-024-08222-1] [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: 03/27/2023] [Accepted: 10/15/2024] [Indexed: 11/22/2024]
Abstract
When humans assemble into face-to-face social networks, they create an extended social environment that permits exposure to the microbiome of others, thereby shaping the composition and diversity of the microbiome at individual and population levels1-6. Here we use comprehensive social network mapping and detailed microbiome sequencing data in 1,787 adults within 18 isolated villages in Honduras7 to investigate the relationship between network structure and gut microbiome composition. Using both species-level and strain-level data, we show that microbial sharing occurs between many relationship types, notably including non-familial and non-household connections. Furthermore, strain-sharing extends to second-degree social connections, suggesting the relevance of a person's broader network. We also observe that socially central people are more microbially similar to the overall village than socially peripheral people. Among 301 people whose microbiome was re-measured 2 years later, we observe greater convergence in strain-sharing in connected versus otherwise similar unconnected co-villagers. Clusters of species and strains occur within clusters of people in village social networks, meaning that social networks provide the social niches within which microbiome biology and phenotypic impact are manifested.
Collapse
Affiliation(s)
- Francesco Beghini
- Yale Institute for Network Science, Yale University, New Haven, CT, USA
| | - Jackson Pullman
- Yale Institute for Network Science, Yale University, New Haven, CT, USA
- Department of Statistics and Data Science, Yale University, New Haven, CT, USA
| | - Marcus Alexander
- Yale Institute for Network Science, Yale University, New Haven, CT, USA
| | - Shivkumar Vishnempet Shridhar
- Yale Institute for Network Science, Yale University, New Haven, CT, USA
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA
| | - Drew Prinster
- Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
| | - Adarsh Singh
- Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA
| | | | - Edoardo M Airoldi
- Department of Statistics, Operations and Data Science, Fox School of Business, Temple University, Philadelphia, PA, USA
- Data Science Institute, Temple University, Philadelphia, PA, USA
| | - Ilana L Brito
- Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA
| | - Nicholas A Christakis
- Yale Institute for Network Science, Yale University, New Haven, CT, USA.
- Department of Statistics and Data Science, Yale University, New Haven, CT, USA.
- Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA.
| |
Collapse
|
|
5
|
Mancin L, Paoli A, Berry S, Gonzalez JT, Collins AJ, Lizarraga MA, Mota JF, Nicola S, Rollo I. Standardization of gut microbiome analysis in sports. Cell Rep Med 2024; 5:101759. [PMID: 39368478 PMCID: PMC11514603 DOI: 10.1016/j.xcrm.2024.101759] [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: 05/14/2024] [Revised: 08/09/2024] [Accepted: 09/10/2024] [Indexed: 10/07/2024]
Abstract
The gut microbiome plays a significant role in physiological functions such as nutrient processing, vitamin production, inflammatory response, and immune modulation, which, in turn, are important contributors to athlete health and performance. To date, the interpretation, discussion, and visualization of microbiome results of athletes are challenging, due to a lack of standard parameters and reference data for collection and comparison. The purpose of this perspective piece is to provide researchers with an easy-to-understand framework for the collection, analysis, and data management related to the gut microbiome with a specific focus on athletic populations. In the absence of a consensus on microbiome research in the sports field, we hope that these considerations serve as foundational "best practice." Adherence to these standard operating procedures will accelerate the path toward improving the quality of data and ultimately our understanding of the influence of the gut microbiome in sport settings.
Collapse
Affiliation(s)
- Laura Mancin
- Department of Biomedical Sciences, University of Padua, Padua, Italy; Human Inspired Technology Research Center HIT, University of Padua, Padua, Italy.
| | - Antonio Paoli
- Department of Biomedical Sciences, University of Padua, Padua, Italy; Human Inspired Technology Research Center HIT, University of Padua, Padua, Italy
| | - Sara Berry
- Department of Nutritional Sciences, King's College London, London, UK
| | | | - Adam J Collins
- Department for Health, University of Bath, BA2 7AY Bath, UK
| | | | - Joao Felipe Mota
- APC Microbiome Ireland, Department of Medicine, School of Microbiology, University College Cork, T12 YT20 Cork, Ireland
| | - Segata Nicola
- Centre for Integrative Biology, University of Trento, Trento, Italy
| | - Ian Rollo
- Gatorade Sports Science Institute, PepsiCo Life Sciences, Global R&D, Leicestershire, UK; School of Sports Exercise and Health Sciences, Loughborough University, Leicestershire, UK
| |
Collapse
|
|
6
|
Ma Z, Zuo T, Frey N, Rangrez AY. A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation. Signal Transduct Target Ther 2024; 9:237. [PMID: 39307902 PMCID: PMC11418828 DOI: 10.1038/s41392-024-01946-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 07/03/2024] [Accepted: 08/01/2024] [Indexed: 09/26/2024] Open
Abstract
The human microbiome is a complex and dynamic system that plays important roles in human health and disease. However, there remain limitations and theoretical gaps in our current understanding of the intricate relationship between microbes and humans. In this narrative review, we integrate the knowledge and insights from various fields, including anatomy, physiology, immunology, histology, genetics, and evolution, to propose a systematic framework. It introduces key concepts such as the 'innate and adaptive genomes', which enhance genetic and evolutionary comprehension of the human genome. The 'germ-free syndrome' challenges the traditional 'microbes as pathogens' view, advocating for the necessity of microbes for health. The 'slave tissue' concept underscores the symbiotic intricacies between human tissues and their microbial counterparts, highlighting the dynamic health implications of microbial interactions. 'Acquired microbial immunity' positions the microbiome as an adjunct to human immune systems, providing a rationale for probiotic therapies and prudent antibiotic use. The 'homeostatic reprogramming hypothesis' integrates the microbiome into the internal environment theory, potentially explaining the change in homeostatic indicators post-industrialization. The 'cell-microbe co-ecology model' elucidates the symbiotic regulation affecting cellular balance, while the 'meta-host model' broadens the host definition to include symbiotic microbes. The 'health-illness conversion model' encapsulates the innate and adaptive genomes' interplay and dysbiosis patterns. The aim here is to provide a more focused and coherent understanding of microbiome and highlight future research avenues that could lead to a more effective and efficient healthcare system.
Collapse
Affiliation(s)
- Ziqi Ma
- Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany.
- DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg, Germany.
| | - Tao Zuo
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China
- Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Norbert Frey
- Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany.
- DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg, Germany.
| | - Ashraf Yusuf Rangrez
- Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Heidelberg, Germany.
- DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg, Germany.
| |
Collapse
|
|
7
|
Zaatry R, Herren R, Gefen T, Geva-Zatorsky N. Microbiome and infectious disease: diagnostics to therapeutics. Microbes Infect 2024; 26:105345. [PMID: 38670215 DOI: 10.1016/j.micinf.2024.105345] [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: 07/13/2023] [Revised: 04/22/2024] [Accepted: 04/22/2024] [Indexed: 04/28/2024]
Abstract
Over 300 years of research on the microbial world has revealed their importance in human health and disease. This review explores the impact and potential of microbial-based detection methods and therapeutic interventions, integrating research of early microbiologists, current findings, and future perspectives.
Collapse
Affiliation(s)
- Rawan Zaatry
- Rappaport Faculty of Medicine, Rappaport Technion Integrated Cancer Center, Technion, Haifa, Israel
| | - Rachel Herren
- Rappaport Faculty of Medicine, Rappaport Technion Integrated Cancer Center, Technion, Haifa, Israel
| | - Tal Gefen
- Rappaport Faculty of Medicine, Rappaport Technion Integrated Cancer Center, Technion, Haifa, Israel
| | - Naama Geva-Zatorsky
- Rappaport Faculty of Medicine, Rappaport Technion Integrated Cancer Center, Technion, Haifa, Israel; CIFAR, Humans & the Microbiome, Toronto, Canada.
| |
Collapse
|
|
8
|
Piperni E, Nguyen LH, Manghi P, Kim H, Pasolli E, Andreu-Sánchez S, Arrè A, Bermingham KM, Blanco-Míguez A, Manara S, Valles-Colomer M, Bakker E, Busonero F, Davies R, Fiorillo E, Giordano F, Hadjigeorgiou G, Leeming ER, Lobina M, Masala M, Maschio A, McIver LJ, Pala M, Pitzalis M, Wolf J, Fu J, Zhernakova A, Cacciò SM, Cucca F, Berry SE, Ercolini D, Chan AT, Huttenhower C, Spector TD, Segata N, Asnicar F. Intestinal Blastocystis is linked to healthier diets and more favorable cardiometabolic outcomes in 56,989 individuals from 32 countries. Cell 2024; 187:4554-4570.e18. [PMID: 38981480 DOI: 10.1016/j.cell.2024.06.018] [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: 05/12/2023] [Revised: 02/23/2024] [Accepted: 06/11/2024] [Indexed: 07/11/2024]
Abstract
Diet impacts human health, influencing body adiposity and the risk of developing cardiometabolic diseases. The gut microbiome is a key player in the diet-health axis, but while its bacterial fraction is widely studied, the role of micro-eukaryotes, including Blastocystis, is underexplored. We performed a global-scale analysis on 56,989 metagenomes and showed that human Blastocystis exhibits distinct prevalence patterns linked to geography, lifestyle, and dietary habits. Blastocystis presence defined a specific bacterial signature and was positively associated with more favorable cardiometabolic profiles and negatively with obesity (p < 1e-16) and disorders linked to altered gut ecology (p < 1e-8). In a diet intervention study involving 1,124 individuals, improvements in dietary quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings suggest a potentially beneficial role for Blastocystis, which may help explain personalized host responses to diet and downstream disease etiopathogenesis.
Collapse
Affiliation(s)
- Elisa Piperni
- Department CIBIO, University of Trento, Trento, Italy; IEO, Istituto Europeo di Oncologia IRCSS, Milan, Italy
| | - Long H Nguyen
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA; Harvard Chan Microbiome in Public Health Center, Boston, MA, USA
| | - Paolo Manghi
- Department CIBIO, University of Trento, Trento, Italy
| | - Hanseul Kim
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA
| | - Edoardo Pasolli
- Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy
| | - Sergio Andreu-Sánchez
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Alberto Arrè
- Department CIBIO, University of Trento, Trento, Italy; Zoe Ltd, London, UK
| | - Kate M Bermingham
- Zoe Ltd, London, UK; Department of Nutritional Sciences, King's College London, London, UK
| | | | - Serena Manara
- Department CIBIO, University of Trento, Trento, Italy
| | | | | | - Fabio Busonero
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy
| | | | - Edoardo Fiorillo
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy
| | | | | | - Emily R Leeming
- Department of Twins Research and Genetic Epidemiology, King's College London, London, UK
| | - Monia Lobina
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy
| | - Marco Masala
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy
| | - Andrea Maschio
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy
| | | | - Mauro Pala
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy
| | - Maristella Pitzalis
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy
| | | | - Jingyuan Fu
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Alexandra Zhernakova
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Simone M Cacciò
- Department of Infectious Diseases, Istituto Superiore Di Sanità, Rome, Italy
| | - Francesco Cucca
- Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Cagliari, Italy; Dipartimento di Scienze Biomediche, Università degli Studi di Sassari, Sassari, Italy
| | - Sarah E Berry
- Department of Nutritional Sciences, King's College London, London, UK
| | - Danilo Ercolini
- Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA; Harvard Chan Microbiome in Public Health Center, Boston, MA, USA
| | - Curtis Huttenhower
- Harvard T.H. Chan School of Public Health, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Tim D Spector
- Department of Twins Research and Genetic Epidemiology, King's College London, London, UK
| | - Nicola Segata
- Department CIBIO, University of Trento, Trento, Italy; IEO, Istituto Europeo di Oncologia IRCSS, Milan, Italy; Department of Twins Research and Genetic Epidemiology, King's College London, London, UK.
| | | |
Collapse
|
|
9
|
Schweitzer M, Wlasak M, Wassermann B, Marcher F, Poglitsch C, Pirker J, Berg G. 'Tiny Biome Tales': A gamified review about the influence of lifestyle choices on the human microbiome. Microb Biotechnol 2024; 17:e14544. [PMID: 39119866 PMCID: PMC11310763 DOI: 10.1111/1751-7915.14544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 07/23/2024] [Indexed: 08/10/2024] Open
Abstract
In the last two decades, new discoveries from microbiome research have changed our understanding of human health. It became evident that daily habits and lifestyle choices shape the human microbiome and ultimately determine health or disease. Therefore, we developed 'Tiny Biome Tales' (https://microbiome.gamelabgraz.at/), a science pedagogy video game designed like a scientific review based exclusively on peer-reviewed articles, to teach about the influence of lifestyle choices on the human microbiome during pregnancy, early and adult life, and related health consequences. Despite the scientific character, it can be played by a broad audience. Here, we also present a scientific assessment and showed that playing the game significantly contributed to knowledge gain. The innovative style of the 'gamified review' represents an ideal platform to disseminate future findings from microbiome research by updating existing and adding new scenes to the game.
Collapse
Affiliation(s)
- Matthias Schweitzer
- Institute of Environmental BiotechnologyGraz University of TechnologyGrazAustria
| | - Maximilian Wlasak
- Institute of Interactive Systems and Data ScienceGraz University of TechnologyGrazAustria
| | - Birgit Wassermann
- Institute of Environmental BiotechnologyGraz University of TechnologyGrazAustria
| | - Florian Marcher
- Institute of Interactive Systems and Data ScienceGraz University of TechnologyGrazAustria
| | - Christian Poglitsch
- Institute of Interactive Systems and Data ScienceGraz University of TechnologyGrazAustria
| | - Johanna Pirker
- Institute of Interactive Systems and Data ScienceGraz University of TechnologyGrazAustria
- Institut für InformatikLudwig‐Maximilians‐UniversitätMunichGermany
| | - Gabriele Berg
- Institute of Environmental BiotechnologyGraz University of TechnologyGrazAustria
- Leibniz Institute for Agricultural Engineering and Bioeconomy (ATB)PotsdamGermany
- Institute for Biochemistry and BiologyUniversity of PotsdamPotsdamGermany
| |
Collapse
|
|
10
|
Zhao Y, Chaw JK, Liu L, Chaw SH, Ang MC, Ting TT. Systematic literature review on reinforcement learning in non-communicable disease interventions. Artif Intell Med 2024; 154:102901. [PMID: 38838400 DOI: 10.1016/j.artmed.2024.102901] [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: 03/22/2023] [Revised: 02/21/2024] [Accepted: 06/02/2024] [Indexed: 06/07/2024]
Abstract
There is evidence that reducing modifiable risk factors and strengthening medical and health interventions can reduce early mortality and economic losses from non-communicable diseases (NCDs). Machine learning (ML) algorithms have been successfully applied to preventing and controlling NCDs. Reinforcement learning (RL) is the most promising of these approaches because of its ability to dynamically adapt interventions to NCD disease progression and its commitment to achieving long-term intervention goals. This paper reviews the preferred algorithms, data sources, design details, and obstacles to clinical application in existing studies to facilitate the early application of RL algorithms in clinical practice research for NCD interventions. We screened 40 relevant papers for quantitative and qualitative analysis using the PRISMA review flow diagram. The results show that researchers tend to use Deep Q-Network (DQN) and Actor-Critic as well as their improved or hybrid algorithms to train and validate RL models on retrospective datasets. Often, the patient's physical condition is the main defining parameter of the state space, while interventions are the main defining parameter of the action space. Mostly, changes in the patient's physical condition are used as a basis for immediate rewards to the agent. Various attempts have been made to address the challenges to clinical application, and several approaches have been proposed from existing research. However, as there is currently no universally accepted solution, the use of RL algorithms in clinical practice for NCD interventions necessitates more comprehensive responses to the issues addressed in this paper, which are safety, interpretability, training efficiency, and the technical aspect of exploitation and exploration in RL algorithms.
Collapse
Affiliation(s)
- Yanfeng Zhao
- Institute of Visual Informatics, National University of Malaysia, Bangi, Selangor, Malaysia
| | - Jun Kit Chaw
- Institute of Visual Informatics, National University of Malaysia, Bangi, Selangor, Malaysia.
| | - Lin Liu
- Henan Vocational University of Science and Technology, Zhoukou, Henan, China
| | - Sook Hui Chaw
- Department of Anaesthesiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Mei Choo Ang
- Institute of Visual Informatics, National University of Malaysia, Bangi, Selangor, Malaysia
| | - Tin Tin Ting
- Faculty of Data Science and Information Technology, INTI International University, Nilai, Negeri Sembilan, Malaysia
| |
Collapse
|
|
11
|
Bridge LA, Hernández Vargas JA, Trujillo-Cáceres SJ, Beigrezaei S, Chatelan A, Salehi-Abargouei A, Muka T, Uriza-Pinzón JP, Raeisi-Dehkordi H, Franco OH, Grompone G, Artola Arita V. Two cosmoses, one universe: a narrative review exploring the gut microbiome's role in the effect of urban risk factors on vascular ageing. Maturitas 2024; 184:107951. [PMID: 38471294 DOI: 10.1016/j.maturitas.2024.107951] [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: 10/03/2023] [Revised: 02/06/2024] [Accepted: 02/20/2024] [Indexed: 03/14/2024]
Abstract
In the face of rising global urbanisation, understanding how the associated environment and lifestyle impact public health is a cornerstone for prevention, research, and clinical practice. Cardiovascular disease is the leading cause of morbidity and mortality worldwide, with urban risk factors contributing greatly to its burden. The current narrative review adopts an exposome approach to explore the effect of urban-associated physical-chemical factors (such as air pollution) and lifestyle on cardiovascular health and ageing. In addition, we provide new insights into how these urban-related factors alter the gut microbiome, which has been associated with an increased risk of cardiovascular disease. We focus on vascular ageing, before disease onset, to promote preventative research and practice. We also discuss how urban ecosystems and social factors may interact with these pathways and provide suggestions for future research, precision prevention and management of vascular ageing. Most importantly, future research and decision-making would benefit from adopting an exposome approach and acknowledging the diverse and boundless universe of the microbiome.
Collapse
Affiliation(s)
- Lara Anne Bridge
- Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Juliana Alexandra Hernández Vargas
- Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Silvia Juliana Trujillo-Cáceres
- Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Sara Beigrezaei
- Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Angeline Chatelan
- Geneva School of Health Sciences, HES-SO University of Applied Sciences and Arts Western Switzerland, Geneva, Switzerland
| | - Amin Salehi-Abargouei
- Research Center for Food Hygiene and Safety, Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | - Julieth Pilar Uriza-Pinzón
- Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Hamidreza Raeisi-Dehkordi
- Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Oscar H Franco
- Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | | | - Vicente Artola Arita
- Department of Global Public Health and Bioethics, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
| |
Collapse
|
|
12
|
Algavi YM, Borenstein E. Relative dispersion ratios following fecal microbiota transplant elucidate principles governing microbial migration dynamics. Nat Commun 2024; 15:4447. [PMID: 38789466 PMCID: PMC11126695 DOI: 10.1038/s41467-024-48717-z] [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: 09/12/2023] [Accepted: 05/08/2024] [Indexed: 05/26/2024] Open
Abstract
Microorganisms frequently migrate from one ecosystem to another. Yet, despite the potential importance of this process in modulating the environment and the microbial ecosystem, our understanding of the fundamental forces that govern microbial dispersion is still lacking. Moreover, while theoretical models and in-vitro experiments have highlighted the contribution of species interactions to community assembly, identifying such interactions in vivo, specifically in communities as complex as the human gut, remains challenging. To address this gap, here we introduce a robust and rigorous computational framework, termed Relative Dispersion Ratio (RDR) analysis, and leverage data from well-characterized fecal microbiota transplant trials, to rigorously pinpoint dependencies between taxa during the colonization of human gastrointestinal tract. Our analysis identifies numerous pairwise dependencies between co-colonizing microbes during migration between gastrointestinal environments. We further demonstrate that identified dependencies agree with previously reported findings from in-vitro experiments and population-wide distribution patterns. Finally, we explore metabolic dependencies between these taxa and characterize the functional properties that facilitate effective dispersion. Collectively, our findings provide insights into the principles and determinants of community dynamics following ecological translocation, informing potential opportunities for precise community design.
Collapse
Affiliation(s)
- Yadid M Algavi
- Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Elhanan Borenstein
- Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel.
- The Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv, Israel.
- Santa Fe Institute, Santa Fe, NM, USA.
| |
Collapse
|
|
13
|
Bosch TCG, Wigley M, Colomina B, Bohannan B, Meggers F, Amato KR, Azad MB, Blaser MJ, Brown K, Dominguez-Bello MG, Ehrlich SD, Elinav E, Finlay BB, Geddie K, Geva-Zatorsky N, Giles-Vernick T, Gros P, Guillemin K, Haraoui LP, Johnson E, Keck F, Lorimer J, McFall-Ngai MJ, Nichter M, Pettersson S, Poinar H, Rees T, Tropini C, Undurraga EA, Zhao L, Melby MK. The potential importance of the built-environment microbiome and its impact on human health. Proc Natl Acad Sci U S A 2024; 121:e2313971121. [PMID: 38662573 PMCID: PMC11098107 DOI: 10.1073/pnas.2313971121] [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] [Indexed: 05/18/2024] Open
Abstract
There is increasing evidence that interactions between microbes and their hosts not only play a role in determining health and disease but also in emotions, thought, and behavior. Built environments greatly influence microbiome exposures because of their built-in highly specific microbiomes coproduced with myriad metaorganisms including humans, pets, plants, rodents, and insects. Seemingly static built structures host complex ecologies of microorganisms that are only starting to be mapped. These microbial ecologies of built environments are directly and interdependently affected by social, spatial, and technological norms. Advances in technology have made these organisms visible and forced the scientific community and architects to rethink gene-environment and microbe interactions respectively. Thus, built environment design must consider the microbiome, and research involving host-microbiome interaction must consider the built-environment. This paradigm shift becomes increasingly important as evidence grows that contemporary built environments are steadily reducing the microbial diversity essential for human health, well-being, and resilience while accelerating the symptoms of human chronic diseases including environmental allergies, and other more life-altering diseases. New models of design are required to balance maximizing exposure to microbial diversity while minimizing exposure to human-associated diseases. Sustained trans-disciplinary research across time (evolutionary, historical, and generational) and space (cultural and geographical) is needed to develop experimental design protocols that address multigenerational multispecies health and health equity in built environments.
Collapse
Affiliation(s)
- Thomas C. G. Bosch
- Zoological Institute, University of Kiel, Kiel24118, Germany
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
| | - Mark Wigley
- Graduate School of Architecture, Planning and Preservation, Columbia University, New York, NY10027
| | - Beatriz Colomina
- School of Architecture, Princeton University, Princeton, NJ08544
| | - Brendan Bohannan
- The Institute of Ecology and Evolution, University of Oregon, Eugene, OR97403-5289
| | - Forrest Meggers
- Princeton University School of Architecture & Andlinger Center for Energy and the Environment, Princeton, NJ08540
| | - Katherine R. Amato
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Department of Anthropology, Northwestern University, Evanston, IL60208
| | - Meghan B. Azad
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB R3E 0Z3, Canada
- Department of Community Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P5, Canada
| | - Martin J. Blaser
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Children’s Hospital Research Institute of Manitoba, Winnipeg, MBR3E 3P4, Canada
- Center for Advanced Biotechnology and Medicine at Rutgers Biomedical and Health Sciences, Rutgers University, Piscataway, NJ08854-8021
| | - Kate Brown
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Program in Science, Technology and Society, Massachusetts Institute of Technology, Cambridge, MA02139
| | - Maria Gloria Dominguez-Bello
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ08901
- Department of Anthropology, Rutgers University, New Brunswick, NJ08901
| | - Stanislav Dusko Ehrlich
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Institute of Neurology, University College London, LondonWC1N 3RX, United Kingdom
| | - Eran Elinav
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Systems Immunology Department, Weizmann Institute of Science, Rehovot761000, Israel
- Division of Microbiome & Cancer, Deutsches Krebsforschungszentrum, 69120Heidelberg, Germany
| | - B. Brett Finlay
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Michael Smith Laboratories, University of British Columbia, Vancouver, BCV6T 1Z4, Canada
| | - Kate Geddie
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Medical and Related Sciences Centre, The Canadian Institute for Advanced Research, Toronto, ONM5G 1L7, Canada
| | - Naama Geva-Zatorsky
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Technion Integrated Cancer Center, Technion-Israel Institute of Technology, Haifa3525433, Israel
- Department of Cell Biology and Cancer Science, Technion-Israel Institute of Technology, Haifa3525433, Israel
| | - Tamara Giles-Vernick
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Anthropology & Ecology of Disease Emergence, Institut Pasteur, Université Paris Cité, Paris75015, France
| | - Philippe Gros
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Department of Biochemistry, McGill University, Montreal, QCH3G 1Y6, Canada
| | - Karen Guillemin
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Institute of Molecular Biology, University of Oregon, Eugene, OR97403
| | - Louis-Patrick Haraoui
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Department of Microbiology and Infectious Diseases, Université de Sherbrooke, CanadaJ1E 4K8
| | - Elizabeth Johnson
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- College of Human Ecology, Cornell University, IthakaNY14853
| | - Frédéric Keck
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Laboratoire d’Anthropologie Sociale, Collège de France, Paris75005, France
| | - Jamie Lorimer
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- School of Geography and the Environment, University of Oxford, OX1 3QY, United Kingdom
| | - Margaret J. McFall-Ngai
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Division of Biology and Biological Engineering, Caltech, Pasadena, CA91125
| | - Mark Nichter
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- School of Anthropology, University of Arizona, Tucson, AZ85721
| | - Sven Pettersson
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Nanyang Technological University, Singapore637715, Singapore
| | - Hendrik Poinar
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Department of Anthropology, McMaster University, Hamilton, ONL8S 4M4, Canada
| | - Tobias Rees
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- LIMN, Berkeley, CA94708
| | - Carolina Tropini
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Department of Microbiology and Immunology and School of Biomedical Engineering, University of British Columbia, Vancouver, BCV6T 1Z3, Canada
| | - Eduardo A. Undurraga
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Escuela de Gobierno, Pontificia Universidad Católica de Chile, Santiago7820436, Chile
| | - Liping Zhao
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ08901
| | - Melissa K. Melby
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ONM5G 1M1, Canada
- Department of Anthropology, University of Delaware, Newark, DE19716
| |
Collapse
|
|
14
|
Perdijk O, Azzoni R, Marsland BJ. The microbiome: an integral player in immune homeostasis and inflammation in the respiratory tract. Physiol Rev 2024; 104:835-879. [PMID: 38059886 DOI: 10.1152/physrev.00020.2023] [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: 05/02/2023] [Revised: 11/07/2023] [Accepted: 11/30/2023] [Indexed: 12/08/2023] Open
Abstract
The last decade of microbiome research has highlighted its fundamental role in systemic immune and metabolic homeostasis. The microbiome plays a prominent role during gestation and into early life, when maternal lifestyle factors shape immune development of the newborn. Breast milk further shapes gut colonization, supporting the development of tolerance to commensal bacteria and harmless antigens while preventing outgrowth of pathogens. Environmental microbial and lifestyle factors that disrupt this process can dysregulate immune homeostasis, predisposing infants to atopic disease and childhood asthma. In health, the low-biomass lung microbiome, together with inhaled environmental microbial constituents, establishes the immunological set point that is necessary to maintain pulmonary immune defense. However, in disease perturbations to immunological and physiological processes allow the upper respiratory tract to act as a reservoir of pathogenic bacteria, which can colonize the diseased lung and cause severe inflammation. Studying these host-microbe interactions in respiratory diseases holds great promise to stratify patients for suitable treatment regimens and biomarker discovery to predict disease progression. Preclinical studies show that commensal gut microbes are in a constant flux of cell division and death, releasing microbial constituents, metabolic by-products, and vesicles that shape the immune system and can protect against respiratory diseases. The next major advances may come from testing and utilizing these microbial factors for clinical benefit and exploiting the predictive power of the microbiome by employing multiomics analysis approaches.
Collapse
Affiliation(s)
- Olaf Perdijk
- Department of Immunology, School of Translational Science, Monash University, Melbourne, Victoria, Australia
| | - Rossana Azzoni
- Department of Immunology, School of Translational Science, Monash University, Melbourne, Victoria, Australia
| | - Benjamin J Marsland
- Department of Immunology, School of Translational Science, Monash University, Melbourne, Victoria, Australia
| |
Collapse
|
|
15
|
Sarkar A, McInroy CJA, Harty S, Raulo A, Ibata NGO, Valles-Colomer M, Johnson KVA, Brito IL, Henrich J, Archie EA, Barreiro LB, Gazzaniga FS, Finlay BB, Koonin EV, Carmody RN, Moeller AH. Microbial transmission in the social microbiome and host health and disease. Cell 2024; 187:17-43. [PMID: 38181740 PMCID: PMC10958648 DOI: 10.1016/j.cell.2023.12.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 12/06/2023] [Accepted: 12/06/2023] [Indexed: 01/07/2024]
Abstract
Although social interactions are known to drive pathogen transmission, the contributions of socially transmissible host-associated mutualists and commensals to host health and disease remain poorly explored. We use the concept of the social microbiome-the microbial metacommunity of a social network of hosts-to analyze the implications of social microbial transmission for host health and disease. We investigate the contributions of socially transmissible microbes to both eco-evolutionary microbiome community processes (colonization resistance, the evolution of virulence, and reactions to ecological disturbance) and microbial transmission-based processes (transmission of microbes with metabolic and immune effects, inter-specific transmission, transmission of antibiotic-resistant microbes, and transmission of viruses). We consider the implications of social microbial transmission for communicable and non-communicable diseases and evaluate the importance of a socially transmissible component underlying canonically non-communicable diseases. The social transmission of mutualists and commensals may play a significant, under-appreciated role in the social determinants of health and may act as a hidden force in social evolution.
Collapse
Affiliation(s)
- Amar Sarkar
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA.
| | - Cameron J A McInroy
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA
| | - Siobhán Harty
- Independent, Tandy Court, Spitalfields, Dublin, Ireland
| | - Aura Raulo
- Department of Biology, University of Oxford, Oxford, UK; Department of Computing, University of Turku, Turku, Finland
| | - Neil G O Ibata
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA
| | - Mireia Valles-Colomer
- Department of Medicine and Life Sciences, Pompeu Fabra University, Barcelona, Spain; Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy
| | - Katerina V-A Johnson
- Institute of Psychology, Leiden University, Leiden, the Netherlands; Department of Psychiatry, University of Oxford, Oxford, UK
| | - Ilana L Brito
- Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA
| | - Joseph Henrich
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA
| | - Elizabeth A Archie
- Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, USA
| | - Luis B Barreiro
- Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA; Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA
| | - Francesca S Gazzaniga
- Molecular Pathology Unit, Cancer Center, Massachusetts General Hospital Research Institute, Charlestown, MA, USA; Department of Pathology, Harvard Medical School, Boston, MA, USA
| | - B Brett Finlay
- Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada; Department of Biochemistry, University of British Columbia, Vancouver, BC, Canada
| | - Eugene V Koonin
- National Center for Biotechnology Information, National Library of Medicine, Bethesda, MD, USA
| | - Rachel N Carmody
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA
| | - Andrew H Moeller
- Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY, USA
| |
Collapse
|
|
16
|
Valles-Colomer M, Manghi P, Cumbo F, Masetti G, Armanini F, Asnicar F, Blanco-Miguez A, Pinto F, Punčochář M, Garaventa A, Amoroso L, Ponzoni M, Corrias MV, Segata N. Neuroblastoma is associated with alterations in gut microbiome composition subsequent to maternal microbial seeding. EBioMedicine 2024; 99:104917. [PMID: 38104504 PMCID: PMC10731604 DOI: 10.1016/j.ebiom.2023.104917] [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: 07/12/2023] [Revised: 11/21/2023] [Accepted: 12/01/2023] [Indexed: 12/19/2023] Open
Abstract
BACKGROUND Neuroblastoma is the most frequent extracranial solid tumour in children, accounting for ∼15% of deaths due to cancer in childhood. The most common clinical presentation are abdominal tumours. An altered gut microbiome composition has been linked to multiple cancer types, and reported in murine models of neuroblastoma. Whether children with neuroblastoma display alterations in gut microbiome composition remains unexplored. METHODS We assessed gut microbiome composition by shotgun metagenomic profiling in an observational cross-sectional study on 288 individuals, consisting of patients with a diagnosis of neuroblastoma at disease onset (N = 63), healthy controls matching the patients on the main covariates of microbiome composition (N = 94), healthy siblings of the patients (N = 13), mothers of patients (N = 59), and mothers of the controls (N = 59). We examined taxonomic and functional microbiome composition and mother-infant strain transmission patterns. FINDINGS Patients with neuroblastoma displayed alterations in gut microbiome composition characterised by reduced microbiome richness, decreased relative abundances of 18 species (including Phocaeicola dorei and Bifidobacterium bifidum), enriched protein fermentation and reduced carbohydrate fermentation potential. Using machine learning, we could successfully discriminate patients from controls (AUC = 82%). Healthy siblings did not display such alterations but resembled the healthy control group. No significant differences in maternal microbiome composition nor mother-to-offspring transmission were detected. INTERPRETATION Patients with neuroblastoma display alterations in taxonomic and functional gut microbiome composition, which cannot be traced to differential maternal seeding. Follow-up research should include investigating potential causal links. FUNDING Italian Ministry of Health Ricerca Corrente and Ricerca Finalizzata 5 per mille (to MPonzoni); Fondazione Italiana Neuroblastoma (to MPonzoni); European Research Council (ERC-StG project MetaPG-716575 and ERC-CoG microTOUCH-101045015 to NS); the European H2020 program ONCOBIOME-825410 project (to NS); the National Cancer Institute of the National Institutes of Health 1U01CA230551 (to NS); the Premio Internazionale Lombardia e Ricerca 2019 (to NS); the MIUR Progetti di Ricerca di Rilevante Interesse Nazionale (PRIN) Bando 2017 Grant 2017J3E2W2 (to NS); EMBO ALTF 593-2020 and Knowledge Generation Project from the Spanish Ministry of Science and Innovation (PID2022-139328OA-I00) (to MV-C).
Collapse
Affiliation(s)
- Mireia Valles-Colomer
- Department CIBIO, University of Trento, Trento, Italy; MELIS Department, Pompeu Fabra University, Barcelona, Spain.
| | - Paolo Manghi
- Department CIBIO, University of Trento, Trento, Italy
| | - Fabio Cumbo
- Department CIBIO, University of Trento, Trento, Italy
| | | | | | | | | | | | | | | | | | - Mirco Ponzoni
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Maria Valeria Corrias
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Nicola Segata
- Department CIBIO, University of Trento, Trento, Italy; Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy.
| |
Collapse
|
|
17
|
Abstract
Our perception of microbes has considerably changed since the recognition of their pathogenic potential in the 19th century. The discovery of antibiotics and their subsequent widespread adoption have substantially altered the landscape of medicine, providing us with treatment options for many infectious diseases and enabling the deployment of previously risky interventions (eg, surgical procedures and chemotherapy), while also leading to the rise of AMR. The latter is commonly viewed as the predominant downside of antibiotic use. However, with the increasing recognition that all metazoan organisms rely on a community of microbes (the microbiota) for normal development and for most physiologic processes, the negative impacts of antibiotic use now extend well beyond AMR. Using the iceberg as a metaphor, we argue that the effects of antibiotics on AMR represent the tip of the iceberg, with much greater repercussions stemming from their role in the rise of so-called noncommunicable diseases (including obesity, diabetes, allergic and autoimmune diseases, neurodevelopmental disorders, and certain cancers). We highlight some of the emerging science around the intersection of the microbiome, antibiotic use, and health (including biological costs and future therapeutic avenues), and we advocate a more nuanced approach in evaluating the impacts of proposed antibiotic use, especially in the setting of preexposure and postexposure prophylaxis.
Collapse
Affiliation(s)
- Louis-Patrick Haraoui
- Department of Microbiology and Infectious Diseases, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
- Centre de Recherche Charles-Le Moyne, Greenfield Park, Quebec, Canada
- Humans & the Microbiome Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada
| | - Martin J Blaser
- Humans & the Microbiome Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada
- Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey, USA
- Robert Wood Johnson School of Medicine, Departments of Medicine and Pathology & Laboratory Medicine, New Brunswick, New Jersey, USA
| |
Collapse
|
|
18
|
Liang Y, Li Q, Liu Y, Guo Y, Li Q. Awareness of intratumoral bacteria and their potential application in cancer treatment. Discov Oncol 2023; 14:57. [PMID: 37148441 PMCID: PMC10164222 DOI: 10.1007/s12672-023-00670-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 04/25/2023] [Indexed: 05/08/2023] Open
Abstract
Hitherto, the recognition of the microbiota role in tumorigenesis and clinical studies mostly focused on the intestinal flora. In contrast to the gut microbiome, microorganisms resident in tumor tissue are in close contact with cancer cells and therefore have the potential to have similar or even different functional patterns to the gut flora. Some investigations have shown intratumoral bacteria, which might come from commensal microbiota in mucosal areas including the gastrointestinal tract and oral cavity, or from nearby normal tissues. The existence, origin, and interactions of intratumoral bacteria with the tumor microenvironment all contribute to intratumoral microorganism heterogeneity. Intratumoral bacteria have a significant role in tumor formation. They can contribute to cancer at the genetic level by secreting poisons that directly damage DNA and also intimately related to immune system response at the systemic level. Intratumoral bacteria have an impact on chemotherapy and immunotherapy in cancer. Importantly, various properties of bacteria such as targeting and ease of modification make them powerful candidates for precision therapy, and combining microbial therapies with other therapies is expected to improve the effectiveness of cancer treatment. In this review, we mainly described the heterogeneity and potential sources of intratumoral bacteria, overviewed the important mechanisms by which they were involved in tumor progression, and summarized their potential value in oncology therapy. At last, we highlight the problems of research in this field, and look forward to a new wave of studies using the various applications of intratumoral microorganisms in cancer therapy.
Collapse
Affiliation(s)
- Yin Liang
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China
| | - Qiyan Li
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China
| | - Yulin Liu
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China
| | - Yajie Guo
- Department of Emergency, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China.
| | - Qingjiao Li
- Department of Laboratory Medicine, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518033, China.
| |
Collapse
|
|
19
|
Valles-Colomer M, Menni C, Berry SE, Valdes AM, Spector TD, Segata N. Cardiometabolic health, diet and the gut microbiome: a meta-omics perspective. Nat Med 2023; 29:551-561. [PMID: 36932240 PMCID: PMC11258867 DOI: 10.1038/s41591-023-02260-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 02/16/2023] [Indexed: 03/19/2023]
Abstract
Cardiometabolic diseases have become a leading cause of morbidity and mortality globally. They have been tightly linked to microbiome taxonomic and functional composition, with diet possibly mediating some of the associations described. Both the microbiome and diet are modifiable, which opens the way for novel therapeutic strategies. High-throughput omics techniques applied on microbiome samples (meta-omics) hold the unprecedented potential to shed light on the intricate links between diet, the microbiome, the metabolome and cardiometabolic health, with a top-down approach. However, effective integration of complementary meta-omic techniques is an open challenge and their application on large cohorts is still limited. Here we review meta-omics techniques and discuss their potential in this context, highlighting recent large-scale efforts and the novel insights they provided. Finally, we look to the next decade of meta-omics research and discuss various translational and clinical pathways to improving cardiometabolic health.
Collapse
Affiliation(s)
- Mireia Valles-Colomer
- Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy
| | - Cristina Menni
- Department of Twin Research, King's College London, London, UK
| | - Sarah E Berry
- Department of Nutritional Sciences, King's College London, London, UK
| | - Ana M Valdes
- School of Medicine, University of Nottingham, Nottingham, UK
- Nottingham National Institute for Health Research Biomedical Research Centre, Nottingham, UK
| | - Tim D Spector
- Department of Twin Research, King's College London, London, UK
| | - Nicola Segata
- Department of Cellular, Computational and Integrative Biology, University of Trento, Trento, Italy.
- European Institute of Oncology, Scientific Institute for Research, Hospitalization and Healthcare, Milan, Italy.
| |
Collapse
|
|
20
|
Valles-Colomer M, Blanco-Míguez A, Manghi P, Asnicar F, Dubois L, Golzato D, Armanini F, Cumbo F, Huang KD, Manara S, Masetti G, Pinto F, Piperni E, Punčochář M, Ricci L, Zolfo M, Farrant O, Goncalves A, Selma-Royo M, Binetti AG, Becerra JE, Han B, Lusingu J, Amuasi J, Amoroso L, Visconti A, Steves CM, Falchi M, Filosi M, Tett A, Last A, Xu Q, Qin N, Qin H, May J, Eibach D, Corrias MV, Ponzoni M, Pasolli E, Spector TD, Domenici E, Collado MC, Segata N. The person-to-person transmission landscape of the gut and oral microbiomes. Nature 2023; 614:125-135. [PMID: 36653448 PMCID: PMC9892008 DOI: 10.1038/s41586-022-05620-1] [Citation(s) in RCA: 180] [Impact Index Per Article: 90.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 12/02/2022] [Indexed: 01/19/2023]
Abstract
The human microbiome is an integral component of the human body and a co-determinant of several health conditions1,2. However, the extent to which interpersonal relations shape the individual genetic makeup of the microbiome and its transmission within and across populations remains largely unknown3,4. Here, capitalizing on more than 9,700 human metagenomes and computational strain-level profiling, we detected extensive bacterial strain sharing across individuals (more than 10 million instances) with distinct mother-to-infant, intra-household and intra-population transmission patterns. Mother-to-infant gut microbiome transmission was considerable and stable during infancy (around 50% of the same strains among shared species (strain-sharing rate)) and remained detectable at older ages. By contrast, the transmission of the oral microbiome occurred largely horizontally and was enhanced by the duration of cohabitation. There was substantial strain sharing among cohabiting individuals, with 12% and 32% median strain-sharing rates for the gut and oral microbiomes, and time since cohabitation affected strain sharing more than age or genetics did. Bacterial strain sharing additionally recapitulated host population structures better than species-level profiles did. Finally, distinct taxa appeared as efficient spreaders across transmission modes and were associated with different predicted bacterial phenotypes linked with out-of-host survival capabilities. The extent of microorganism transmission that we describe underscores its relevance in human microbiome studies5, especially those on non-infectious, microbiome-associated diseases.
Collapse
Affiliation(s)
| | | | - Paolo Manghi
- Department CIBIO, University of Trento, Trento, Italy
| | | | | | | | | | - Fabio Cumbo
- Department CIBIO, University of Trento, Trento, Italy
| | - Kun D Huang
- Department CIBIO, University of Trento, Trento, Italy
| | - Serena Manara
- Department CIBIO, University of Trento, Trento, Italy
| | | | | | - Elisa Piperni
- Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy
| | | | - Liviana Ricci
- Department CIBIO, University of Trento, Trento, Italy
| | - Moreno Zolfo
- Department CIBIO, University of Trento, Trento, Italy
| | - Olivia Farrant
- Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Adriana Goncalves
- Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Marta Selma-Royo
- Department CIBIO, University of Trento, Trento, Italy
- Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), Paterna, Valencia, Spain
| | - Ana G Binetti
- Instituto de Lactología Industrial (CONICET-UNL), Facultad de Ingeniería Química, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - Jimmy E Becerra
- Grupo de Investigación Alimentación y Comportamiento Humano, Universidad Metropolitana, Barranquilla, Colombia
| | - Bei Han
- School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, China
| | - John Lusingu
- National Institute for Medical Research, Tanga Medical Research Centre, Tanga, Tanzania
| | - John Amuasi
- Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
| | | | - Alessia Visconti
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - Claire M Steves
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - Mario Falchi
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | | | - Adrian Tett
- Department CIBIO, University of Trento, Trento, Italy
- Centre for Microbiology and Environmental Systems Science, University of Vienna, Vienna, Austria
| | - Anna Last
- Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
| | - Qian Xu
- Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
- Realbio Genomics Institute, Shanghai, China
| | - Nan Qin
- Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
- Realbio Genomics Institute, Shanghai, China
| | - Huanlong Qin
- Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jürgen May
- Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
| | - Daniel Eibach
- Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
| | - Maria Valeria Corrias
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Mirco Ponzoni
- Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Genoa, Italy
| | - Edoardo Pasolli
- Department of Agricultural Sciences, University of Naples 'Federico II', Portici, Italy
| | - Tim D Spector
- Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
| | - Enrico Domenici
- Department CIBIO, University of Trento, Trento, Italy
- Centre for Computational and Systems Biology (COSBI), Microsoft Research Foundation, Rovereto, Italy
| | - Maria Carmen Collado
- Institute of Agrochemistry and Food Technology-National Research Council (IATA-CSIC), Paterna, Valencia, Spain
| | - Nicola Segata
- Department CIBIO, University of Trento, Trento, Italy.
- Department of Experimental Oncology, IEO European Institute of Oncology IRCCS, Milan, Italy.
| |
Collapse
|
|
21
|
Mills S, Yang B, Smith GJ, Stanton C, Ross RP. Efficacy of Bifidobacterium longum alone or in multi-strain probiotic formulations during early life and beyond. Gut Microbes 2023; 15:2186098. [PMID: 36896934 PMCID: PMC10012958 DOI: 10.1080/19490976.2023.2186098] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 02/24/2023] [Indexed: 03/11/2023] Open
Abstract
The significance of Bifidobacterium to human health can be appreciated from its early colonization of the neonatal gut, where Bifidobacterium longum represents the most abundant species. While its relative abundance declines with age, it is further reduced in several diseases. Research into the beneficial properties of B. longum has unveiled a range of mechanisms, including the production of bioactive molecules, such as short-chain fatty acids, polysaccharides, and serine protease inhibitors. From its intestinal niche, B. longum can have far-reaching effects in the body influencing immune responses in the lungs and even skin, as well as influencing brain activity. In this review, we present the biological and clinical impacts of this species on a range of human conditions beginning in neonatal life and beyond. The available scientific evidence reveals a strong rationale for continued research and further clinical trials that investigate the ability of B. longum to treat or prevent a range of diseases across the human lifespan.
Collapse
Affiliation(s)
- Susan Mills
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Bo Yang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | | | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Food Biosciences Department, Teagasc Food Research Centre, Co Cork, Ireland
| | - R. Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| |
Collapse
|
|
22
|
Garcia S, Ordoñez S, López-Molina VM, Lacruz-Pleguezuelos B, Carrillo de Santa Pau E, Marcos-Zambrano LJ. Citizen science helps to raise awareness about gut microbiome health in people at risk of developing non-communicable diseases. Gut Microbes 2023; 15:2241207. [PMID: 37530428 PMCID: PMC10399471 DOI: 10.1080/19490976.2023.2241207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 07/20/2023] [Indexed: 08/03/2023] Open
Abstract
Citizens lack knowledge about the impact of gut microbiota on health and how lifestyle and dietary choices can influence it, leading to Non-Communicable Diseases (NCDs) and affecting overall well-being. Participatory action research (PAR) is a promising approach to enhance communication and encourage individuals to adopt healthier behaviors and improve their health. In this study, we explored the feasibility of integrating the photovoice method with citizen science approaches to assess the impact of social and environmental factors on gut microbiota health. In this context, citizen science approaches entailed the involvement of participants in the collection of samples for subsequent analysis, specifically gut microbiome assessment via 16S rRNA gene sequencing. We recruited 70 volunteers and organized six photovoice groups based on age and educational background. Participants selected 64 photographs that represented the influence of daily habits on gut microbiota health and created four photovoice themes. Analysis of the gut microbiome using 16S rRNA gene sequencing identified 474 taxa, and in-depth microbial analysis revealed three clusters of people based on gut microbiome diversity and body mass index (BMI). Our findings indicate that participants enhanced their knowledge of gut microbiome health through PAR activities, and we found a correlation between lower microbial diversity, higher BMI, and better achievement of learning outcomes. Using PAR as a methodology is an effective way to increase citizens' awareness and engagement in self-care, maintain healthy gut microbiota, and prevent NCD development. These interventions are particularly beneficial for individuals at higher risk of developing NCDs.
Collapse
Affiliation(s)
- Silvia Garcia
- Computational Biology Group, Precision Nutrition and Cancer Research Program, IMDEA Food Institute, Madrid, Spain
| | - Sheyla Ordoñez
- Computational Biology Group, Precision Nutrition and Cancer Research Program, IMDEA Food Institute, Madrid, Spain
| | - Victor Manuel López-Molina
- Computational Biology Group, Precision Nutrition and Cancer Research Program, IMDEA Food Institute, Madrid, Spain
| | - Blanca Lacruz-Pleguezuelos
- Computational Biology Group, Precision Nutrition and Cancer Research Program, IMDEA Food Institute, Madrid, Spain
| | | | - Laura Judith Marcos-Zambrano
- Computational Biology Group, Precision Nutrition and Cancer Research Program, IMDEA Food Institute, Madrid, Spain
| |
Collapse
|
|
23
|
Wang H, Yang M, Cheng S, Ren Y, Deng Y, Liang J, Lin X, Li J, Yin J, Wu Q. The Spouses of Stroke Patients Have a Similar Oral Microbiome to Their Partners with an Elevated Risk of Stroke. Microorganisms 2022; 10:2288. [PMID: 36422358 PMCID: PMC9697374 DOI: 10.3390/microorganisms10112288] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/09/2022] [Accepted: 11/16/2022] [Indexed: 01/19/2024] Open
Abstract
Spousal members who share no genetic relatedness show similar oral microbiomes. Whether a shared microbiome increases the risk of cerebrovascular disease is challenging to investigate. The aim of this study was to compare the oral microbiota composition of poststroke patients, their partners, and controls and to compare the risk of stroke between partners of poststroke patients and controls. Forty-seven pairs of spouses and 34 control subjects were recruited for the study. Alcohol use, smoking, metabolic disease history, clinical test results, and oral health were documented. Oral microbiome samples were measured by 16S rRNA gene sequencing. The risk of stroke was measured by risk factor assessment (RFA) and the Framingham Stroke Profile (FSP). Poststroke patients and their partners exhibited higher alpha diversity than controls. Principal-coordinate analysis (PCoA) showed that poststroke patients share a more similar microbiota composition with their partners than controls. The differentially abundant microbial taxa among the 3 groups were identified by linear discriminant analysis effect size (LEfSe) analysis. The risk factor assessment indicated that partners of poststroke patients had a higher risk of stroke than controls. Spearman correlation analysis showed that Prevotellaceae was negatively associated with RFA. Lactobacillales was negatively associated with FSP, while Campilobacterota and [Eubacterium]_nodatum_group were positively associated with FSP. These results suggest that stroke risk may be transmissible between spouses through the oral microbiome, in which several bacteria might be involved in the pathogenesis of stroke.
Collapse
Affiliation(s)
- Huidi Wang
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Mengjia Yang
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Sanping Cheng
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Yueran Ren
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Yiting Deng
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Jingru Liang
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Xiaofei Lin
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Jie Li
- Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Jia Yin
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Qiheng Wu
- Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| |
Collapse
|
|
24
|
Kim KS. Regulation of T cell repertoires by commensal microbiota. Front Cell Infect Microbiol 2022; 12:1004339. [PMID: 36310871 PMCID: PMC9606468 DOI: 10.3389/fcimb.2022.1004339] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 09/20/2022] [Indexed: 11/25/2022] Open
Abstract
The gut microbiota plays an important role in regulating the host immune systems. It is well established that various commensal microbial species can induce the differentiation of CD4+ T helper subsets such as Foxp3+ regulatory T (Treg) cells and Th17 cells in antigen-dependent manner. The ability of certain microbial species to induce either Treg cells or Th17 cells is often linked to the altered susceptibility to certain immune disorders that are provoked by aberrant T cell response against self-antigens. These findings raise an important question as to how gut microbiota can regulate T cell repertoire and the activation of autoreactive T cells. This review will highlight microbiota-dependent regulation of thymic T cell development, maintenance of T cell repertoire in the secondary lymphoid tissues and the intestine, and microbiota-mediated modulation of autoreactive and tumor neoantigen-specific T cells in autoimmune diseases and tumors, respectively.
Collapse
|
|
25
|
Kumar A, Sakhare K, Bhattacharya D, Chattopadhyay R, Parikh P, Narayan KP, Mukherjee A. Communication in non-communicable diseases (NCDs) and role of immunomodulatory nutraceuticals in their management. Front Nutr 2022; 9:966152. [PMID: 36211513 PMCID: PMC9532975 DOI: 10.3389/fnut.2022.966152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 08/11/2022] [Indexed: 12/24/2022] Open
Abstract
Conveyance of pathogens between organisms causes communicable diseases. On the other hand, a non-communicable disease (NCD) was always thought to have no causative transmissible infective agents. Today, this clear distinction is increasingly getting blurred and NCDs are found to be associated with some transmissible components. The human microbiota carries a congregation of microbes, the majority and the most widely studied being bacteria in the gut. The adult human gut harbors ginormous inhabitant microbes, and the microbiome accommodates 150-fold more genes than the host genome. Microbial communities share a mutually beneficial relationship with the host, especially with respect to host physiology including digestion, immune responses, and metabolism. This review delineates the connection between environmental factors such as infections leading to gut dysbiosis and NCDs and explores the evidence regarding possible causal link between them. We also discuss the evidence regarding the value of appropriate therapeutic immunomodulatory nutritional interventions to reduce the development of such diseases. We behold such immunomodulatory effects have the potential to influence in various NCDs and restore homeostasis. We believe that the beginning of the era of microbiota-oriented personalized treatment modalities is not far away.
Collapse
Affiliation(s)
- Abhiram Kumar
- Esperer Onco Nutrition Pvt. Ltd., Mumbai, India
- Department of Biological Sciences, Birla Institute of Technology and Science – Pilani, Hyderabad, India
| | - Kalyani Sakhare
- Department of Biological Sciences, Birla Institute of Technology and Science – Pilani, Hyderabad, India
| | - Dwaipayan Bhattacharya
- Department of Biological Sciences, Birla Institute of Technology and Science – Pilani, Hyderabad, India
| | | | - Purvish Parikh
- Department of Clinical Haematology, Mahatma Gandhi Medical College and Hospital, Jaipur, India
| | - Kumar P. Narayan
- Department of Biological Sciences, Birla Institute of Technology and Science – Pilani, Hyderabad, India
- *Correspondence: Kumar P. Narayan,
| | | |
Collapse
|
|
26
|
Bu F, Yao X, Lu Z, Yuan X, Chen C, Li L, Li Y, Jiang F, Zhu L, Shi G, Chen Y. Pathogenic or Therapeutic: The Mediating Role of Gut Microbiota in Non-Communicable Diseases. Front Cell Infect Microbiol 2022; 12:906349. [PMID: 35873168 PMCID: PMC9301375 DOI: 10.3389/fcimb.2022.906349] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 06/10/2022] [Indexed: 11/18/2022] Open
Abstract
Noncommunicable diseases (NCDs) lead to 41 million deaths every year and account for 71% of all deaths worldwide. Increasing evidence indicates that gut microbiota disorders are closely linked to the occurrence and development of diseases. The gut microbiota, as a potential transmission medium, could play a key role in the transmission and treatment of diseases. The gut microbiota makes noncommunicable diseases communicable. New methods of the prevention and treatment of these diseases could be further explored through the gut microbiota.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Yugen Chen
- *Correspondence: Yugen Chen, ; Guoping Shi,
| |
Collapse
|
|
27
|
Tan JS, Ren JM, Fan L, Wei Y, Hu S, Zhu SS, Yang Y, Cai J. Genetic Predisposition of Anti-Cytomegalovirus Immunoglobulin G Levels and the Risk of 9 Cardiovascular Diseases. Front Cell Infect Microbiol 2022; 12:884298. [PMID: 35832381 PMCID: PMC9272786 DOI: 10.3389/fcimb.2022.884298] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 05/23/2022] [Indexed: 12/20/2022] Open
Abstract
Background Accumulating evidence has indicated that persistent human cytomegalovirus (HCMV) infection is associated with several cardiovascular diseases including atherosclerosis and coronary artery disease. However, whether there is a causal association between the level of anti-HCMV immune response and the risk of cardiovascular diseases remains unknown. Methods Single-nucleotide polymorphisms associated with anti-cytomegalovirus immunoglobulin (Ig) G levels were used as instrumental variables to estimate the causal effect of anti-cytomegalovirus IgG levels on 9 cardiovascular diseases (including atrial fibrillation, coronary artery disease, hypertension, heart failure, peripheral artery disease, pulmonary embolism, deep vein thrombosis of the lower extremities, rheumatic valve diseases, and non-rheumatic valve diseases). For each cardiovascular disease, Mendelian randomization (MR) analyses were performed. Inverse variance-weighted meta-analysis (IVW) with a random-effects model was used as a principal analysis. In addition to this, the weighted median approach and MR-Egger method were used for further sensitivity analysis. Results In the IVW analysis, genetically predicted anti-cytomegalovirus IgG levels were suggestively associated with coronary artery disease with an odds ratio (OR) of 1.076 [95% CI, 1.009–1.147; p = 0.025], peripheral artery disease (OR 1.709; 95% CI, 1.039–2.812; p = 0.035), and deep vein thrombosis (OR 1.002; 95% CI, 1.000–1.004; p = 0.025). In the further analysis, similar causal associations were obtained from weighted median analysis and MR-Egger analysis with lower precision. No notable heterogeneities and horizontal pleiotropies were observed (p > 0.05). Conclusions/Interpretation Our findings first provide direct evidence that genetic predisposition of anti-cytomegalovirus IgG levels increases the risk of coronary artery disease, peripheral artery disease, and deep vein thrombosis.
Collapse
Affiliation(s)
- Jiang-Shan Tan
- Emergency Center, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jia-Meng Ren
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education. Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, China
| | - Luyun Fan
- Hypertension Center, FuWai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yuhao Wei
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China
| | - Song Hu
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sheng-Song Zhu
- Center for Respiratory and Pulmonary Vascular Diseases, Department of Cardiology, Key Laboratory of Pulmonary Vascular Medicine, National Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanmin Yang
- Emergency Center, Fuwai Hospital, National Center for Cardiovascular Diseases, National Clinical Research Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Yangmin Yang, ; Jun Cai,
| | - Jun Cai
- Hypertension Center, FuWai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- *Correspondence: Yangmin Yang, ; Jun Cai,
| |
Collapse
|
|
28
|
Wensel CR, Pluznick JL, Salzberg SL, Sears CL. Next-generation sequencing: insights to advance clinical investigations of the microbiome. J Clin Invest 2022; 132:e154944. [PMID: 35362479 PMCID: PMC8970668 DOI: 10.1172/jci154944] [Citation(s) in RCA: 193] [Impact Index Per Article: 64.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Next-generation sequencing (NGS) technology has advanced our understanding of the human microbiome by allowing for the discovery and characterization of unculturable microbes with prediction of their function. Key NGS methods include 16S rRNA gene sequencing, shotgun metagenomic sequencing, and RNA sequencing. The choice of which NGS methodology to pursue for a given purpose is often unclear for clinicians and researchers. In this Review, we describe the fundamentals of NGS, with a focus on 16S rRNA and shotgun metagenomic sequencing. We also discuss pros and cons of each methodology as well as important concepts in data variability, study design, and clinical metadata collection. We further present examples of how NGS studies of the human microbiome have advanced our understanding of human disease pathophysiology across diverse clinical contexts, including the development of diagnostics and therapeutics. Finally, we share insights as to how NGS might further be integrated into and advance microbiome research and clinical care in the coming years.
Collapse
Affiliation(s)
| | - Jennifer L. Pluznick
- Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Steven L. Salzberg
- Department of Biomedical Engineering
- Department of Computer Science, and
- Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland, USA
| | - Cynthia L. Sears
- Department of Medicine and
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| |
Collapse
|
|
29
|
Fan L, Ren J, Chen Y, Wang Y, Guo Z, Bu P, Yang J, Ma W, Zhu B, Zhao Y, Cai J. Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study. Trials 2022; 23:178. [PMID: 35209934 PMCID: PMC8867679 DOI: 10.1186/s13063-022-06086-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Accepted: 02/05/2022] [Indexed: 12/15/2022] Open
Abstract
Background Hypertension is currently the leading modifiable cause of global morbidity and mortality, leading to substantial health and financial burdens. Although multiple studies of management models and innovative therapeutic strategies for hypertension have been conducted, there are still gaps in the field, with a poor control rate reflecting a lack of novel, effective, clinically translated medication or intervention options. Recent animal and human studies repeatedly confirmed a link between the microbiota and hypertension. Of note is our previous study establishing a cause-and-effect relationship between the gut microbiota and blood pressure elevation. A hypothesis of gut microbiota intervention for treating hypertension is thus postulated, and fecal microbiota transplantation (FMT) from healthy donors was performed. Methods A multicenter, randomized, placebo-controlled, blinded clinical trial will be performed in 120 grade 1 hypertensive patients for 3 months. All recruited patients will be randomly assigned in a 1:1 ratio to take oral FMT capsules or placebo capsules on day 1, day 7, and day 14 and will be followed up on day 30, day 60, and day 90. The primary outcome is the change in office systolic blood pressure from baseline to day 30. The main secondary outcomes are BP indicators, including changes in systolic and diastolic blood pressure from office and 24-h ambulatory blood pressure monitoring; assessments of ankle-branchial index and pulse wave velocity; profiling of fecal microbial composition and function; profiling of fecal and serum metabolome; changes in levels of blood glucose, blood lipids, and body mass index; and assessment of adverse events as a measure of safety. Discussion Expanding upon our previous research on the role of the gut microbiota in the pathogenesis of hypertension, this study serves as a clinical translation advancement and explores the potential of fecal microbiota transplantation for treating hypertension. The underlying mechanisms, particularly the roles of specific microorganisms or their postbiotics in blood pressure amelioration, will also be investigated via multiple approaches, such as metagenomic sequencing and metabolomic profiling. Trial registration ClinicalTrials.govNCT04406129. Registered on May 28, 2020
Collapse
Affiliation(s)
- Luyun Fan
- Hypertension Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Ren
- Shanxi Bethune Hospital, Taiyuan, Shanxi, China
| | - Youren Chen
- The Second Affiliated Hospital of Shantou University, Shantou, Guangdong, China
| | - Yang Wang
- Medical Research & Biometrics Center, National Center for Cardiovascular Diseases, Fuwai Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Zihong Guo
- Fuwai Yunnan Cardiovascular Hospital, Kunming, Yunnan, China
| | - Peili Bu
- Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Jinfeng Yang
- The People's Hospital of Ji Xian District, Tianjin, China
| | - Wenjun Ma
- Hypertension Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bingpo Zhu
- Southern University of Science and Technology Hospital, Shenzhen, China
| | - Yanyan Zhao
- Medical Research & Biometrics Center, National Center for Cardiovascular Diseases, Fuwai Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Jun Cai
- Hypertension Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| |
Collapse
|
|
30
|
García-Río F, Alcázar-Navarrete B, Castillo-Villegas D, Cilloniz C, García-Ortega A, Leiro-Fernández V, Lojo-Rodriguez I, Padilla-Galo A, Quezada-Loaiza CA, Rodriguez-Portal JA, Sánchez-de-la-Torre M, Sibila O, Martínez-García MA. [Translated article] Biological Biomarkers in Respiratory Diseases. ARCHIVOS DE BRONCONEUMOLOGÍA 2022. [DOI: 10.1016/j.arbres.2022.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
31
|
Moya-Alvarez V, Sansonetti PJ. Understanding the pathways leading to gut dysbiosis and enteric environmental dysfunction in infants: the influence of maternal dysbiosis and other microbiota determinants during early life. FEMS Microbiol Rev 2022; 46:6516326. [PMID: 35088084 DOI: 10.1093/femsre/fuac004] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 12/10/2021] [Accepted: 01/25/2022] [Indexed: 11/13/2022] Open
Abstract
Maternal environmental enteric dysfunction (EED) encompasses undernutrition with an inflammatory gut profile, a variable degree of dysbiosis and increased translocation of pathogens in the gut mucosa. Even though recent research findings have shed light on the pathological pathways underlying the establishment of the infant gut dysbiosis, evidence on how maternal EED influences the development of gut dysbiosis and EED in the offspring remains elusive. This review summarizes the current knowledge on the effect of maternal dysbiosis and EED on infant health, and explores recent progress in unraveling the mechanisms of acquisition of a dysbiotic gut microbiota in the offspring. In Western communities, maternal inoculum, delivery mode, perinatal antibiotics, feeding practices, and infections are the major drivers of the infant gut microbiota during the first two years of life. In other latitudes, the infectious burden and maternal malnutrition might introduce further risk factors for infant gut dysbiosis. Novel tools, such as transcriptomics and metabolomics, have become indispensable to analyze the metabolic environment of the infant in utero and post-partum. Human-milk oligosaccharides have essential prebiotic, antimicrobial, and anti-biofilm properties that might offer additional therapeutic opportunities.
Collapse
Affiliation(s)
- Violeta Moya-Alvarez
- Molecular Microbial Pathogenesis - INSERM U1202, Department of Cell Biology and Infection, 28 rue du Dr. Roux, Institut Pasteur, 75015 Paris, France.,Epidemiology of Emergent Diseases Unit, Global Health Department, 25 rue du Dr. Roux, Institut Pasteur, 75015 Paris, France
| | - Philippe J Sansonetti
- Molecular Microbial Pathogenesis - INSERM U1202, Department of Cell Biology and Infection, 28 rue du Dr. Roux, Institut Pasteur, 75015 Paris, France.,Chaire de Microbiologie et Maladies Infectieuses, Collège de France, Paris, France.,The Center for Microbes, Development and Health, Institut Pasteur de Shanghai, China
| |
Collapse
|
|
32
|
Garcia-Rio F, Alcázar B, Castillo D, Cilloniz C, García-Ortega A, Leiro-Fernández V, Lojo-Rodriguez I, Padilla A, Quezada CA, Rodriguez-Portal JA, Sánchez-de-la-Torre M, Sibila O, Martinez-Garcia MA. Biomarcadores biológicos en las enfermedades respiratorias. Arch Bronconeumol 2022; 58:323-333. [DOI: 10.1016/j.arbres.2022.01.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/11/2022] [Accepted: 01/11/2022] [Indexed: 11/26/2022]
|
|
33
|
Anisman H, Kusnecov AW. Microbiota and health. Cancer 2022. [DOI: 10.1016/b978-0-323-91904-3.00003-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
|
|
34
|
Thingholm LB, Bang C, Rühlemann MC, Starke A, Sicks F, Kaspari V, Jandowsky A, Frölich K, Ismer G, Bernhard A, Bombis C, Struve B, Rausch P, Franke A. Ecology impacts the decrease of Spirochaetes and Prevotella in the fecal gut microbiota of urban humans. BMC Microbiol 2021; 21:276. [PMID: 34635060 PMCID: PMC8504008 DOI: 10.1186/s12866-021-02337-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 09/27/2021] [Indexed: 02/07/2023] Open
Abstract
Compared to the huge microbial diversity in most mammals, human gut microbiomes have lost diversity while becoming specialized for animal-based diets – especially compared to chimps, their genetically closest ancestors. The lowered microbial diversity within the gut of westernized populations has also been associated with different kinds of chronic inflammatory diseases in humans. To further deepen our knowledge on phylogenetic and ecologic impacts on human health and fitness, we established the herein presented biobank as well as its comprehensive microbiota analysis. In total, 368 stool samples from 38 different animal species, including Homo sapiens, belonging to four diverse mammalian orders were collected at seven different locations and analyzed by 16S rRNA gene amplicon sequencing. Comprehensive data analysis was performed to (i) determine the overall impact of host phylogeny vs. diet, location, and ecology and to (ii) examine the general pattern of fecal bacterial diversity across captive mammals and humans. By using a controlled study design with captive mammals we could verify that host phylogeny is the most dominant driver of mammalian gut microbiota composition. However, the effect of ecology appears to be able to overcome host phylogeny and should therefore be studied in more detail in future studies. Most importantly, our study could observe a remarkable decrease of Spirochaetes and Prevotella in westernized humans and platyrrhines, which is probably not only due to diet, but also to the social behavior and structure in these communities. Our study highlights the importance of phylogenetic relationship and ecology within the evolution of mammalian fecal microbiota composition. Particularly, the observed decrease of Spirochaetes and Prevotella in westernized communities might be associated to lifestyle dependent rapid evolutionary changes, potentially involved in the establishment of dysbiotic microbiomes, which promote the etiology of chronic diseases.
Collapse
Affiliation(s)
- Louise B Thingholm
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Campus Kiel, Rosalind-Franklin-Str, 12, 24105, Kiel, Germany
| | - Corinna Bang
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Campus Kiel, Rosalind-Franklin-Str, 12, 24105, Kiel, Germany
| | - Malte C Rühlemann
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Campus Kiel, Rosalind-Franklin-Str, 12, 24105, Kiel, Germany
| | - Annika Starke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Campus Kiel, Rosalind-Franklin-Str, 12, 24105, Kiel, Germany
| | - Florian Sicks
- Tierpark Berlin-Friedrichsfelde GmbH, Berlin, Germany
| | - Verena Kaspari
- Tierparkvereinigung Neumuenster e.V, Neumuenster, Germany
| | | | | | | | | | - Claudia Bombis
- Tierpark Hagenbeck Gemeinnützige Gesellschaft mbH, Hamburg, Germany
| | - Barbara Struve
- Leintalzoo Schwaigern, Freudenmühle 1, 74193, Schwaigern, Germany
| | - Philipp Rausch
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Campus Kiel, Rosalind-Franklin-Str, 12, 24105, Kiel, Germany.,Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Campus Kiel, Rosalind-Franklin-Str, 12, 24105, Kiel, Germany. .,University Hospital Schleswig Holstein (UKSH), Campus Kiel, Kiel, Germany.
| |
Collapse
|
|
35
|
Sharma SP, Suk KT, Kim DJ. Significance of gut microbiota in alcoholic and non-alcoholic fatty liver diseases. World J Gastroenterol 2021; 27:6161-6179. [PMID: 34712025 PMCID: PMC8515797 DOI: 10.3748/wjg.v27.i37.6161] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 07/05/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Liver-gut communication is vital in fatty liver diseases, and gut microbes are the key regulators in maintaining liver homeostasis. Chronic alcohol abuse and persistent overnutrition create dysbiosis in gut ecology, which can contribute to fatty liver disease. In this review, we discuss the gut microbial compositional changes that occur in alcoholic and nonalcoholic fatty liver diseases and how this gut microbial dysbiosis and its metabolic products are involved in fatty liver disease pathophysiology. We also summarize the new approaches related to gut microbes that might help in the diagnosis and treatment of fatty liver disease.
Collapse
Affiliation(s)
- Satya Priya Sharma
- Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon 24252, South Korea
| | - Ki Tae Suk
- Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon 24252, South Korea
| | - Dong Joon Kim
- Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon 24252, South Korea
| |
Collapse
|
|
36
|
Blaschke S, Carl J, Ellinger J, Birner U, Mess F. The Role of Physical Activity-Related Health Competence and Leisure-Time Physical Activity for Physical Health and Metabolic Syndrome: A Structural Equation Modeling Approach for German Office Workers. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:10153. [PMID: 34639454 PMCID: PMC8507877 DOI: 10.3390/ijerph181910153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/21/2021] [Accepted: 09/22/2021] [Indexed: 01/07/2023]
Abstract
Office workers (OWs) are prone to insufficient physical activity (PA), which increases their risk of metabolic syndrome (MetS) and impaired physical health. The Physical Activity-related Health Competence (PAHCO) model holds the potential to facilitate a healthy physically active lifestyle. Therefore, in this study, we investigate the interplay between PAHCO, leisure-time PA, physical health, and MetS in OWs in Germany. In a cross-sectional study, OWs (N = 316, 25% female) completed self-report questionnaires along with an occupational health checkup to examine their Metabolic Syndrome Severity Score (MetSSS) values. Structural equation modeling indicated a strong positive association between PAHCO and leisure-time PA and a small positive association with physical health. PAHCO showed a considerable negative association with the MetSSS. Leisure-time PA was a positive mediator for the PAHCO-physical health association but was not a significant mediator for the association between PAHCO and the MetSSS. These findings underscore the importance of PAHCO in the context of leisure-time PA, physical health, and MetS in OWs. Furthermore, our findings highlight the health-enhancing value of the qualitative aspects of PA, such as motivational and volitional components in PA participation, with respect to physical health and MetS.
Collapse
Affiliation(s)
- Simon Blaschke
- Department of Sport and Health Sciences, Technical University of Munich, 80992 Munich, Germany; (J.E.); (F.M.)
| | - Johannes Carl
- Department of Sport Science and Sport, Friedrich-Alexander University Erlangen-Nürnberg, 91058 Erlangen, Germany;
| | - Jan Ellinger
- Department of Sport and Health Sciences, Technical University of Munich, 80992 Munich, Germany; (J.E.); (F.M.)
| | - Ulrich Birner
- Siemens AG, Human Resources EHS, Department of Psychosocial Health and Well-Being, Otto-Hahn-Ring 6, 81739 Munich, Germany;
| | - Filip Mess
- Department of Sport and Health Sciences, Technical University of Munich, 80992 Munich, Germany; (J.E.); (F.M.)
| |
Collapse
|
|
37
|
Aguilera-Méndez A, Boone-Villa D, Nieto-Aguilar R, Villafaña-Rauda S, Molina AS, Sobrevilla JV. Role of vitamins in the metabolic syndrome and cardiovascular disease. Pflugers Arch 2021; 474:117-140. [PMID: 34518916 DOI: 10.1007/s00424-021-02619-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 08/14/2021] [Accepted: 08/30/2021] [Indexed: 12/25/2022]
Abstract
The prevalence of metabolic syndrome and cardiovascular disease has increased and continues to be the leading cause of mortality worldwide. The etiology of these diseases includes a complex phenotype derived from interactions between genetic, environmental, and nutritional factors. In this regard, it is common to observe vitamin deficiencies in the general population and even more in patients with cardiometabolic diseases due to different factors. Vitamins are essential micronutrients for cellular metabolism and their deficiencies result in diseases. In addition to its role in nutritional functions, increasingly, vitamins are being recognized as modulators of genetics expression and signals transduction, when consumed at pharmacological concentrations. Numerous randomized preclinical and clinical trials have evaluated the use of vitamin supplementation in the prevention and treatment of metabolic syndrome and cardiovascular disease. However, it is controversy regarding its efficacy in the treatment and prevention of these diseases. In this review, we investigated chemical basics, physiological effect and recommended daily intake, problems with deficiency and overdose, preclinical and clinical studies, and mechanisms of action of vitamin supplementation in the treatment and prevention of metabolic syndrome and cardiovascular disease.
Collapse
Affiliation(s)
- Asdrubal Aguilera-Méndez
- Institute of Biological Chemistry Research, Universidad Michoacana de San Nicolás de Hidalgo, Av. J. Mújica, Edificio B3, Ciudad Universitaria, CP, 58030, Morelia, Michoacán, México.
| | - Daniel Boone-Villa
- School of Medicine, North Section, Universidad Autónoma de Coahuila, Piedras Negras, 26090, Coahuila, México
| | - Renato Nieto-Aguilar
- University Center for Postgraduate Studies and Research, School of Dentistry, Universidad Michoacana de San Nicolás de Hidalgo, 58337, Morelia, Michoacán, México
| | - Santiago Villafaña-Rauda
- Postgraduate Section, Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, México
| | - Alfredo Saavedra Molina
- Institute of Biological Chemistry Research, Universidad Michoacana de San Nicolás de Hidalgo, Av. J. Mújica, Edificio B3, Ciudad Universitaria, CP, 58030, Morelia, Michoacán, México
| | - Janeth Ventura Sobrevilla
- School of Medicine, North Section, Universidad Autónoma de Coahuila, Piedras Negras, 26090, Coahuila, México
| |
Collapse
|
|
38
|
Zhuang P, Li H, Jia W, Shou Q, Zhu Y, Mao L, Wang W, Wu F, Chen X, Wan X, Wu Y, Liu X, Li Y, Zhu F, He L, Chen J, Zhang Y, Jiao J. Eicosapentaenoic and docosahexaenoic acids attenuate hyperglycemia through the microbiome-gut-organs axis in db/db mice. MICROBIOME 2021; 9:185. [PMID: 34507608 PMCID: PMC8434703 DOI: 10.1186/s40168-021-01126-6] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 07/08/2021] [Indexed: 05/04/2023]
Abstract
BACKGROUND Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been suggested to prevent the development of metabolic disorders. However, their individual role in treating hyperglycemia and the mechanism of action regarding gut microbiome and metabolome in the context of diabetes remain unclear. RESULTS Supplementation of DHA and EPA attenuated hyperglycemia and insulin resistance without changing body weight in db/db mice while the ameliorative effect appeared to be more pronounced for EPA. DHA/EPA supplementation reduced the abundance of the lipopolysaccharide-containing Enterobacteriaceae whereas elevated the family Coriobacteriaceae negatively correlated with glutamate level, genera Barnesiella and Clostridium XlVa associated with bile acids production, beneficial Bifidobacterium and Lactobacillus, and SCFA-producing species. The gut microbiome alterations co-occurred with the shifts in the metabolome, including glutamate, bile acids, propionic/butyric acid, and lipopolysaccharide, which subsequently relieved β cell apoptosis, suppressed hepatic gluconeogenesis, and promoted GLP-1 secretion, white adipose beiging, and insulin signaling. All these changes appeared to be more evident for EPA. Furthermore, transplantation with DHA/EPA-mediated gut microbiota mimicked the ameliorative effect of DHA/EPA on glucose homeostasis in db/db mice, together with similar changes in gut metabolites. In vitro, DHA/EPA treatment directly inhibited the growth of Escherichia coli (Family Enterobacteriaceae) while promoted Coriobacterium glomerans (Family Coriobacteriaceae), demonstrating a causal effect of DHA/EPA on featured gut microbiota. CONCLUSIONS DHA and EPA dramatically attenuated hyperglycemia and insulin resistance in db/db mice, which was mediated by alterations in gut microbiome and metabolites linking gut to adipose, liver and pancreas. These findings shed light into the gut-organs axis as a promising target for restoring glucose homeostasis and also suggest a better therapeutic effect of EPA for treating diabetes. Video abstract.
Collapse
Affiliation(s)
- Pan Zhuang
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Haoyu Li
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Wei Jia
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Qiyang Shou
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310005, Zhejiang, China
| | - Ya'er Zhu
- Analysis Center of Agrobiology and Environmental Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Lei Mao
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China
| | - Wenqiao Wang
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China
| | - Fei Wu
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China
| | - Xiaoqian Chen
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Xuzhi Wan
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Yuqi Wu
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Xiaohui Liu
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China
| | - Yin Li
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China
| | - Fanghuan Zhu
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Lilin He
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Jingnan Chen
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China
| | - Yu Zhang
- National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, Zhejiang, China.
| | - Jingjing Jiao
- Department of Nutrition, School of Public Health, Department of Clinical Nutrition of Affiliated Second Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, Zhejiang, China.
| |
Collapse
|
|
39
|
Society to cell: How child poverty gets “Under the Skin” to influence child development and lifelong health. DEVELOPMENTAL REVIEW 2021. [DOI: 10.1016/j.dr.2021.100983] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
|
|
40
|
Dietert RR. Microbiome First Medicine in Health and Safety. Biomedicines 2021; 9:biomedicines9091099. [PMID: 34572284 PMCID: PMC8468398 DOI: 10.3390/biomedicines9091099] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 08/16/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Microbiome First Medicine is a suggested 21st century healthcare paradigm that prioritizes the entire human, the human superorganism, beginning with the microbiome. To date, much of medicine has protected and treated patients as if they were a single species. This has resulted in unintended damage to the microbiome and an epidemic of chronic disorders [e.g., noncommunicable diseases and conditions (NCDs)]. Along with NCDs came loss of colonization resistance, increased susceptibility to infectious diseases, and increasing multimorbidity and polypharmacy over the life course. To move toward sustainable healthcare, the human microbiome needs to be front and center. This paper presents microbiome-human physiology from the view of systems biology regulation. It also details the ongoing NCD epidemic including the role of existing drugs and other factors that damage the human microbiome. Examples are provided for two entryway NCDs, asthma and obesity, regarding their extensive network of comorbid NCDs. Finally, the challenges of ensuring safety for the microbiome are detailed. Under Microbiome-First Medicine and considering the importance of keystone bacteria and critical windows of development, changes in even a few microbiota-prioritized medical decisions could make a significant difference in health across the life course.
Collapse
Affiliation(s)
- Rodney R Dietert
- Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853, USA
| |
Collapse
|
|
41
|
Knippel RJ, Drewes JL, Sears CL. The Cancer Microbiome: Recent Highlights and Knowledge Gaps. Cancer Discov 2021; 11:2378-2395. [PMID: 34400408 DOI: 10.1158/2159-8290.cd-21-0324] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/12/2021] [Accepted: 06/08/2021] [Indexed: 02/07/2023]
Abstract
Knowledge of the human microbiome, which is likely a critical factor in the initiation, progression, and prognosis of multiple forms of cancer, is rapidly expanding. In this review, we focus on recent investigations to discern putative, causative microbial species and the microbiome composition and structure currently associated with procarcinogenesis and tumorigenesis at select body sites. We specifically highlight forms of cancer, gastrointestinal and nongastrointestinal, that have significant bacterial associations and well-defined experimental evidence with the aim of generating directions for future experimental and translational investigations to develop a clearer understanding of the multifaceted mechanisms by which microbiota affect cancer formation. SIGNIFICANCE: Emerging and, for some cancers, strong experimental and translational data support the contribution of the microbiome to cancer biology and disease progression. Disrupting microbiome features and pathways contributing to cancer may provide new approaches to improving cancer outcomes in patients.
Collapse
Affiliation(s)
- Reece J Knippel
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Julia L Drewes
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Cynthia L Sears
- Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland.
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, Maryland
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| |
Collapse
|
|
42
|
Olowoyo P, Popoola F, Yaria J, Akinyemi R, Maffia P, Owolabi MO. Strategies for Reducing Non-Communicable Diseases in Africa. Pharmacol Res 2021; 170:105736. [PMID: 34147659 PMCID: PMC8800856 DOI: 10.1016/j.phrs.2021.105736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Affiliation(s)
- Paul Olowoyo
- Department of Medicine, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti and Federal Teaching Hospital, Ido-Ekiti, Nigeria
| | - Femi Popoola
- Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Nigeria
| | - Joseph Yaria
- Department of Medicine, University College Hospital, Ibadan, Nigeria
| | - Rufus Akinyemi
- Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Nigeria; Department of Medicine, University College Hospital, Ibadan, Nigeria
| | - Pasquale Maffia
- Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom; Department of Pharmacy, University of Naples Federico II, Naples, Italy
| | - Mayowa Ojo Owolabi
- Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Nigeria; Department of Medicine, University College Hospital, Ibadan, Nigeria.
| |
Collapse
|
|
43
|
Moreira-Rosário A, Marques C, Pinheiro H, Araújo JR, Ribeiro P, Rocha R, Mota I, Pestana D, Ribeiro R, Pereira A, de Sousa MJ, Pereira-Leal J, de Sousa J, Morais J, Teixeira D, Rocha JC, Silvestre M, Príncipe N, Gatta N, Amado J, Santos L, Maltez F, Boquinhas A, de Sousa G, Germano N, Sarmento G, Granja C, Póvoa P, Faria A, Calhau C. Gut Microbiota Diversity and C-Reactive Protein Are Predictors of Disease Severity in COVID-19 Patients. Front Microbiol 2021; 12:705020. [PMID: 34349747 PMCID: PMC8326578 DOI: 10.3389/fmicb.2021.705020] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/10/2021] [Indexed: 12/15/2022] Open
Abstract
The risk factors for coronavirus disease 2019 (COVID-19) severity are still poorly understood. Considering the pivotal role of the gut microbiota on host immune and inflammatory functions, we investigated the association between changes in the gut microbiota composition and the clinical severity of COVID-19. We conducted a multicenter cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: (1) the WHO Clinical Progression Scale-mild, 19 (16.5%); moderate, 37 (32.2%); or severe, 59 (51.3%), and (2) the location of recovery from COVID-19-ambulatory, 14 (household isolation, 12.2%); hospitalized in ward, 40 (34.8%); or hospitalized in the intensive care unit, 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing, and the data obtained were further related to the clinical parameters of COVID-19 patients. The risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison to mild COVID-19 patients, the gut microbiota of moderate and severe patients have: (a) lower Firmicutes/Bacteroidetes ratio; (b) higher abundance of Proteobacteria; and (c) lower abundance of beneficial butyrate-producing bacteria such as the genera Roseburia and Lachnospira. Multivariable regression analysis showed that the Shannon diversity index [odds ratio (OR) = 2.85, 95% CI = 1.09-7.41, p = 0.032) and C-reactive protein (OR = 3.45, 95% CI = 1.33-8.91, p = 0.011) are risk factors for severe COVID-19 (a score of 6 or higher in the WHO Clinical Progression Scale). In conclusion, our results demonstrated that hospitalized patients with moderate and severe COVID-19 have microbial signatures of gut dysbiosis; for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker of COVID-19 severity.
Collapse
Affiliation(s)
- André Moreira-Rosário
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Cláudia Marques
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Hélder Pinheiro
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Department of Infectious Diseases, Hospital Curry Cabral, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
| | - João Ricardo Araújo
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Pedro Ribeiro
- Centro de Medicina Laboratorial Germano de Sousa, Lisboa, Portugal
| | - Rita Rocha
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.,Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal
| | - Inês Mota
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Diogo Pestana
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Rita Ribeiro
- Centro de Medicina Laboratorial Germano de Sousa, Lisboa, Portugal
| | - Ana Pereira
- Centro de Medicina Laboratorial Germano de Sousa, Lisboa, Portugal
| | - Maria José de Sousa
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Centro de Medicina Laboratorial Germano de Sousa, Lisboa, Portugal
| | | | - José de Sousa
- Centro de Medicina Laboratorial Germano de Sousa, Lisboa, Portugal
| | - Juliana Morais
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal.,Faculdade de Ciências Médicas, Comprehensive Health Research Centre (CHRC), NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Diana Teixeira
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, Comprehensive Health Research Centre (CHRC), NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Júlio César Rocha
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Marta Silvestre
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Nuno Príncipe
- Department of Emergency and Intensive Care Medicine, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Nuno Gatta
- Department of Emergency and Intensive Care Medicine, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - José Amado
- Department of Emergency and Intensive Care Medicine, Centro Hospitalar Universitário de São João, Porto, Portugal
| | - Lurdes Santos
- Infectious Diseases Service, ID Intensive Care Unit, Faculdade de Medicina, Centro Hospitalar Universitário de São João, Universidade do Porto, Porto, Portugal
| | - Fernando Maltez
- Department of Infectious Diseases, Hospital Curry Cabral, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
| | - Ana Boquinhas
- Department of Emergency, CUF Infante Santo Hospital, Lisboa, Portugal
| | - Germano de Sousa
- Centro de Medicina Laboratorial Germano de Sousa, Lisboa, Portugal
| | - Nuno Germano
- Polyvalent Intensive Care Unit, Hospital Curry Cabral, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
| | - Gonçalo Sarmento
- Department of Internal Medicine, Centro Hospitalar de Entre o Douro e Vouga, Santa Maria da Feira, Portugal
| | - Cristina Granja
- Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal.,Department of Anesthesiology, Centro Hospitalar Universitário de São João, Porto, Portugal.,Department of Surgery and Physiology, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
| | - Pedro Póvoa
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Polyvalent Intensive Care Unit, Hospital São Francisco Xavier, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal.,Center for Clinical Epidemiology, Research Unit of Clinical Epidemiology, OUH Odense University Hospital, Odense, Denmark
| | - Ana Faria
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, Comprehensive Health Research Centre (CHRC), NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| | - Conceição Calhau
- Faculdade de Ciências M dicas, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal.,Faculdade de Ciências Médicas, CINTESIS - Center for Health Technology and Services Research, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal
| |
Collapse
|
|
44
|
Ralli T, Neupane YR, Saifi Z, Kohli K. Gut microbiota as an emerging therapeutic avenue for the treatment of non-alcoholic fatty liver disease. Curr Pharm Des 2021; 27:4677-4685. [PMID: 34176456 DOI: 10.2174/1389201022666210625141526] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 05/10/2021] [Indexed: 12/02/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of death related to liver diseases worldwide. Despite this, there is no specific treatment that is approved for the disease till now, which could be due to a poor understanding of the pathophysiology of this disease. In the past few decades, several scientists have speculated the root cause of NAFLD to be dysbalance in the gut microbiome resulting in a susceptibility totheinflammatory cascade in the liver. Herein, we hypothesize to fabricate a novel formulation containing prebiotic with probiotics, which, thereby would help in maintaining the gut homeostasis, and used for the treatment of NAFLD. The proposed novel formulation would contain a Bifidobacteriumsp. with Faecalibacteriumprausnitzii in the presence of a dietary fibre having hepatoprotective activity. These two strains of probiotics would help in increasing the concentration of butyrate in the gut, which in turn would inhibit intestinal inflammation and maintain gut integrity. The dietary fibre would serve a dual mechanism; firstly they would act as a prebiotic, which helps in the proliferation of administered probiotics and secondly, would protect the liver via own hepatoprotective action. This combinatorial approach would pave a new therapeutic avenue for the treatment of NAFLD.
Collapse
Affiliation(s)
- Tanya Ralli
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, JamiaHamdard, New Delhi, India
| | - Yub Raj Neupane
- Department of Pharmacy, National University of Singapore, Singapore
| | - Zoya Saifi
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, JamiaHamdard, New Delhi, India
| | - Kanchan Kohli
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, JamiaHamdard, New Delhi, India
| |
Collapse
|
|
45
|
Lv BM, Quan Y, Zhang HY. Causal Inference in Microbiome Medicine: Principles and Applications. Trends Microbiol 2021; 29:736-746. [PMID: 33895062 DOI: 10.1016/j.tim.2021.03.015] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 03/25/2021] [Accepted: 03/26/2021] [Indexed: 12/12/2022]
Abstract
Microorganisms that colonize the mammalian skin and cavity play critical roles in various physiological functions of the host. Numerous studies have revealed strong associations between the microbiota and multiple diseases. However, association does not mean causation. To clarify the mechanisms underlying microbiota-mediated diseases, research is moving from associative analyses to causation studies. In this article, we first introduce the principles of the computational methods for causal inference, and then discuss the applications of these methods in microbiome medicine. Furthermore, we examine the reliability of theoretically inferred causality by the interventionist framework. Finally, we show the potential of confirmed causality in microbiota-targeted therapy, especially in personalized dietary intervention. We conclude that a comprehensive understanding of the causal relationships between diets, microbiota, host targets, and diseases is critical to future microbiome medicine.
Collapse
Affiliation(s)
- Bo-Min Lv
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P. R. China
| | - Yuan Quan
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P. R. China
| | - Hong-Yu Zhang
- Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, P. R. China.
| |
Collapse
|
|
46
|
Catania F, Baedke J, Fábregas-Tejeda A, Nieves Delgado A, Vitali V, Long LAN. Global climate change, diet, and the complex relationship between human host and microbiome: Towards an integrated picture. Bioessays 2021; 43:e2100049. [PMID: 33829521 DOI: 10.1002/bies.202100049] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 03/12/2021] [Accepted: 03/16/2021] [Indexed: 02/06/2023]
Abstract
Dietary changes can alter the human microbiome with potential detrimental consequences for health. Given that environment, health, and evolution are interconnected, we ask: Could diet-driven microbiome perturbations have consequences that extend beyond their immediate impact on human health? We address this question in the context of the urgent health challenges posed by global climate change. Drawing on recent studies, we propose that not only can diet-driven microbiome changes lead to dysbiosis, they can also shape life-history traits and fuel human evolution. We posit that dietary shifts prompt mismatched microbiome-host genetics configurations that modulate human longevity and reproductive success. These mismatches can also induce a heritable intra-holobiont stress response, which encourages the holobiont to re-establish equilibrium within the changed nutritional environment. Thus, while mismatches between climate change-related genetic and epigenetic configurations within the holobiont increase the risk and severity of diseases, they may also affect life-history traits and facilitate adaptive responses. These propositions form a framework that can help systematize and address climate-related dietary challenges for policy and health interventions.
Collapse
Affiliation(s)
- Francesco Catania
- Institute for Evolution and Biodiversity, University of Münster, Münster, Germany
| | - Jan Baedke
- Department of Philosophy I, Ruhr University Bochum, Bochum, Germany
| | | | - Abigail Nieves Delgado
- Knowledge, Technology & Innovation, Wageningen University, Wageningen, The Netherlands.,Freudenthal Institute, Utrecht University, Utrecht, The Netherlands
| | - Valerio Vitali
- Institute for Evolution and Biodiversity, University of Münster, Münster, Germany
| | - Le Anh Nguyen Long
- Department of Public Administration, University of Twente, Enschede, The Netherlands
| |
Collapse
|
|
47
|
Finlay BB, Amato KR, Azad M, Blaser MJ, Bosch TCG, Chu H, Dominguez-Bello MG, Ehrlich SD, Elinav E, Geva-Zatorsky N, Gros P, Guillemin K, Keck F, Korem T, McFall-Ngai MJ, Melby MK, Nichter M, Pettersson S, Poinar H, Rees T, Tropini C, Zhao L, Giles-Vernick T. The hygiene hypothesis, the COVID pandemic, and consequences for the human microbiome. Proc Natl Acad Sci U S A 2021; 118:e2010217118. [PMID: 33472859 PMCID: PMC8017729 DOI: 10.1073/pnas.2010217118] [Citation(s) in RCA: 95] [Impact Index Per Article: 23.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Indexed: 12/12/2022] Open
Abstract
The COVID-19 pandemic has the potential to affect the human microbiome in infected and uninfected individuals, having a substantial impact on human health over the long term. This pandemic intersects with a decades-long decline in microbial diversity and ancestral microbes due to hygiene, antibiotics, and urban living (the hygiene hypothesis). High-risk groups succumbing to COVID-19 include those with preexisting conditions, such as diabetes and obesity, which are also associated with microbiome abnormalities. Current pandemic control measures and practices will have broad, uneven, and potentially long-term effects for the human microbiome across the planet, given the implementation of physical separation, extensive hygiene, travel barriers, and other measures that influence overall microbial loss and inability for reinoculation. Although much remains uncertain or unknown about the virus and its consequences, implementing pandemic control practices could significantly affect the microbiome. In this Perspective, we explore many facets of COVID-19-induced societal changes and their possible effects on the microbiome, and discuss current and future challenges regarding the interplay between this pandemic and the microbiome. Recent recognition of the microbiome's influence on human health makes it critical to consider both how the microbiome, shaped by biosocial processes, affects susceptibility to the coronavirus and, conversely, how COVID-19 disease and prevention measures may affect the microbiome. This knowledge may prove key in prevention and treatment, and long-term biological and social outcomes of this pandemic.
Collapse
Affiliation(s)
- B Brett Finlay
- Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada;
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
| | - Katherine R Amato
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Anthropology, Northwestern University, Evanston, IL 60208
| | - Meghan Azad
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Manitoba Interdisciplinary Lactation Centre, Children's Hospital Research Institute of Manitoba, Winnipeg, MB R3E 3P4, Canada
| | - Martin J Blaser
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Center for Advanced Biotechnology and Medicine at Rutgers Biomedical and Health Sciences, Rutgers University, Piscataway, NJ 08854-8021
| | - Thomas C G Bosch
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Zoologisches Institut, University of Kiel, 24118 Kiel, Germany
| | - Hiutung Chu
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Pathology, University of California San Diego, La Jolla, CA 92093
| | - Maria Gloria Dominguez-Bello
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ 08901
| | - Stanislav Dusko Ehrlich
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Metagenopolis Unit, French National Institute for Agricultural Research, 78350 Jouy-en-Josas, France
| | - Eran Elinav
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Immunology, Weizmann Institute of Science, Rehovot 761000, Israel
- Cancer-Microbiome Division, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany
| | - Naama Geva-Zatorsky
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Technion Integrated Cancer Center, Department of Cell Biology and Cancer Science, Technion-Israel Institute of Technology, Haifa 3525433, Israel
| | - Philippe Gros
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Biochemistry, McGill University, Montreal, QC H3G 1Y6, Canada
| | - Karen Guillemin
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Institute of Molecular Biology, University of Oregon, Eugene, OR 97403
| | - Frédéric Keck
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Centre National de la Recherche Scientifique, 75016 Paris, France
- Laboratoire d'Anthropologie Sociale, Collège de France, 75005 Paris, France
| | - Tal Korem
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Systems Biology, Irving Cancer Research Center, Columbia University, New York, NY 10032
- Department of Obstetrics and Gynecology, Irving Cancer Research Center, Columbia University, New York, NY 10032
| | - Margaret J McFall-Ngai
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Pacific Biosciences Research Center, University of Hawai'i at Manoa, Honolulu, HI 96822
| | - Melissa K Melby
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Anthropology, University of Delaware, Newark, DE 19711
| | - Mark Nichter
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Anthropology, University of Arizona, Tucson, AZ 85721
| | - Sven Pettersson
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Lee Kong Chian School of Medicine, Nanyang Technological University, 637715 Singapore
| | - Hendrik Poinar
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Anthropology, McMaster University, Hamilton, ON L8S 4M4, Canada
| | - Tobias Rees
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Transformations of the Human Program, Berggruen Institute, Los Angeles, CA 90013
| | - Carolina Tropini
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- School of Biomedical Engineering, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
- Department of Microbiology & Immunology, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
| | - Liping Zhao
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada
- Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ 08901
| | - Tamara Giles-Vernick
- Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, ON M5G 1M1, Canada;
- Anthropology & Ecology of Disease Emergence, Institut Pasteur, 75015 Paris, France
| |
Collapse
|
|
48
|
Mentis AFA, Dardiotis E, Efthymiou V, Chrousos GP. Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews. BMC Med 2021; 19:6. [PMID: 33435977 PMCID: PMC7805241 DOI: 10.1186/s12916-020-01873-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Accepted: 11/26/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The etiologies of chronic neurological diseases, which heavily contribute to global disease burden, remain far from elucidated. Despite available umbrella reviews on single contributing factors or diseases, no study has systematically captured non-purely genetic risk and/or protective factors for chronic neurological diseases. METHODS We performed a systematic analysis of umbrella reviews (meta-umbrella) published until September 20th, 2018, using broad search terms in MEDLINE, SCOPUS, Web of Science, Cochrane Database of Systematic Reviews, Cumulative Index to Nursing and Allied Health Literature, ProQuest Dissertations & Theses, JBI Database of Systematic Reviews and Implementation Reports, DARE, and PROSPERO. The PRISMA guidelines were followed for this study. Reference lists of the identified umbrella reviews were also screened, and the methodological details were assessed using the AMSTAR tool. For each non-purely genetic factor association, random effects summary effect size, 95% confidence and prediction intervals, and significance and heterogeneity levels facilitated the assessment of the credibility of the epidemiological evidence identified. RESULTS We identified 2797 potentially relevant reviews, and 14 umbrella reviews (203 unique meta-analyses) were eligible. The median number of primary studies per meta-analysis was 7 (interquartile range (IQR) 7) and that of participants was 8873 (IQR 36,394). The search yielded 115 distinctly named non-genetic risk and protective factors with a significant association, with various strengths of evidence. Mediterranean diet was associated with lower risk of dementia, Alzheimer disease (AD), cognitive impairment, stroke, and neurodegenerative diseases in general. In Parkinson disease (PD) and AD/dementia, coffee consumption, and physical activity were protective factors. Low serum uric acid levels were associated with increased risk of PD. Smoking was associated with elevated risk of multiple sclerosis and dementia but lower risk of PD, while hypertension was associated with lower risk of PD but higher risk of dementia. Chronic occupational exposure to lead was associated with higher risk of amyotrophic lateral sclerosis. Late-life depression was associated with higher risk of AD and any form of dementia. CONCLUSIONS We identified several non-genetic risk and protective factors for various neurological diseases relevant to preventive clinical neurology, health policy, and lifestyle counseling. Our findings could offer new perspectives in secondary research (meta-research).
Collapse
Affiliation(s)
- Alexios-Fotios A Mentis
- Public Health Laboratories, Hellenic Pasteur Institute, Athens, Greece; and, Department of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece.
| | - Efthimios Dardiotis
- Department of Neurology, University Hospital of Larissa, University of Thessaly, Larissa, Greece
| | - Vasiliki Efthymiou
- University Research Institute of Maternal and Child Health and Precision Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - George P Chrousos
- University Research Institute of Maternal and Child Health and Precision Medicine, and UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
49
|
Giron MC, Mazzi U. Molecular imaging of microbiota-gut-brain axis: searching for the right targeted probe for the right target and disease. Nucl Med Biol 2021; 92:72-77. [PMID: 33262001 DOI: 10.1016/j.nucmedbio.2020.11.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/05/2020] [Accepted: 11/11/2020] [Indexed: 12/16/2022]
Abstract
The highly bidirectional dialogue between the gut and the brain is markedly stimulated and influenced by the microbiome through integrated neuroendocrine, neurological and immunological processes. Gut microbiota itself communicate with the host producing hormonal intermediates, metabolites, proteins, and toxins responsible for a variety of biochemical and functional inputs, thereby shaping host homeostasis. Indeed, a dysregulated microbiota-gut-brain axis might be the origin of many neuroimmune-mediated disorders, e.g. autism, multiple sclerosis, depression, Alzheimer's and Parkinson's disease, which appear months or even years prior to a diagnosis, corroborating the theory that the pathological process is spread from the gut to the brain. A much deeper comprehension of how commensal microbe can be manipulated to interfere with disease progression is crucial for developing new strategies to diagnose and treat diseases. In recent years, the potential of positron-emission-tomography (PET) in the field of bacteria detection has gained attention. The uptake of several PET tracers has been evaluated to investigate infection pathophysiology, e.g. sterile or pathogen-mediated infection, monitoring of progression, or as a surrogate endpoint in clinical trials. In this minireview, we briefly describe the role of microbiome-gut-brain axis in health and disease and we discuss the imaging modalities and agents that could be applied to study the dynamic interactions between microbiome, gut and brain. These are key aspects in understanding the biochemical lexicon underpinning the microbiome-host crosstalk that would enable the development of diagnostics and therapeutics by targeting the human microbiota.
Collapse
Affiliation(s)
- Maria Cecilia Giron
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Italy.
| | - Ulderico Mazzi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Italy
| |
Collapse
|
|
50
|
Schelkle B, Galland Q. Microbiome Research: Open Communication Today, Microbiome Applications in the Future. Microorganisms 2020; 8:E1960. [PMID: 33322055 PMCID: PMC7763060 DOI: 10.3390/microorganisms8121960] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 11/27/2020] [Accepted: 12/08/2020] [Indexed: 11/16/2022] Open
Abstract
Microbiome research has recently gained centre-stage in both basic science and translational applications, yet researchers often feel that public communication about its potential overpromises. This manuscript aims to share a perspective on how scientists can engage in more open, ethical and transparent communication using an ongoing research project on food systems microbiomes as a case study. Concrete examples of strategically planned communication efforts are outlined, which aim to inspire and empower other researchers. Finally, we conclude with a discussion on the benefits of open and transparent communication from early-on in innovation pathways, mainly increasing trust in scientific processes and thus paving the way to achieving societal milestones such as the UN Sustainable Development Goals and the EU Green Deal.
Collapse
Affiliation(s)
- Bettina Schelkle
- European Food Information Council, Rue des Deux Eglises 14, 1000 Brussels, Belgium
| | - Quentin Galland
- Hague Corporate Affairs, Rue Belliard 40, 1040 Brussels, Belgium;
| |
Collapse
|