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      Emerging Priorities for Microbiome Research

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          Abstract

          Microbiome research has increased dramatically in recent years, driven by advances in technology and significant reductions in the cost of analysis. Such research has unlocked a wealth of data, which has yielded tremendous insight into the nature of the microbial communities, including their interactions and effects, both within a host and in an external environment as part of an ecological community. Understanding the role of microbiota, including their dynamic interactions with their hosts and other microbes, can enable the engineering of new diagnostic techniques and interventional strategies that can be used in a diverse spectrum of fields, spanning from ecology and agriculture to medicine and from forensics to exobiology. From June 19–23 in 2017, the NIH and NSF jointly held an Innovation Lab on Quantitative Approaches to Biomedical Data Science Challenges in our Understanding of the Microbiome . This review is inspired by some of the topics that arose as priority areas from this unique, interactive workshop. The goal of this review is to summarize the Innovation Lab’s findings by introducing the reader to emerging challenges, exciting potential, and current directions in microbiome research. The review is broken into five key topic areas: (1) interactions between microbes and the human body, (2) evolution and ecology of microbes, including the role played by the environment and microbe-microbe interactions, (3) analytical and mathematical methods currently used in microbiome research, (4) leveraging knowledge of microbial composition and interactions to develop engineering solutions, and (5) interventional approaches and engineered microbiota that may be enabled by selectively altering microbial composition. As such, this review seeks to arm the reader with a broad understanding of the priorities and challenges in microbiome research today and provide inspiration for future investigation and multi-disciplinary collaboration.

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          Structure, Function and Diversity of the Healthy Human Microbiome

          Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin, and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics, and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analyzed the largest cohort and set of distinct, clinically relevant body habitats to date. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families, and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology, and translational applications of the human microbiome.
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            Diet rapidly and reproducibly alters the human gut microbiome

            Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut 1–5 , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals 2 , reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease 6 . In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
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              Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms

              DNA sequencing continues to decrease in cost with the Illumina HiSeq2000 generating up to 600 Gb of paired-end 100 base reads in a ten-day run. Here we present a protocol for community amplicon sequencing on the HiSeq2000 and MiSeq Illumina platforms, and apply that protocol to sequence 24 microbial communities from host-associated and free-living environments. A critical question as more sequencing platforms become available is whether biological conclusions derived on one platform are consistent with what would be derived on a different platform. We show that the protocol developed for these instruments successfully recaptures known biological results, and additionally that biological conclusions are consistent across sequencing platforms (the HiSeq2000 versus the MiSeq) and across the sequenced regions of amplicons.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                19 February 2020
                2020
                : 11
                : 136
                Affiliations
                [1] 1School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, PA, United States
                [2] 2The School District of Philadelphia , Philadelphia, PA, United States
                [3] 3Department of Infectious Diseases, J. Craig Venter Institute , La Jolla, CA, United States
                [4] 4Department of Nutrition, Dietetics and Food Sciences, Utah State University , Logan, UT, United States
                [5] 5Ecological and Evolutionary Signal-processing and Informatics Laboratory (EESI), Electrical and Computer Engineering, Drexel University , Philadelphia, PA, United States
                [6] 6College of Medicine, Drexel University , Philadelphia, PA, United States
                [7] 7Nexus Group, Faculty of Information Science and Technology, Gi-CoRE Station for Big Data & Cybersecurity, Hokkaido University , Sapporo, Japan
                [8] 8Department of Biological Science, Florida State University , Tallahassee, FL, United States
                [9] 9Department of Civil Engineering, New Mexico State University , Las Cruces, NM, United States
                [10] 10Department of Microbiology, The Ohio State University , Columbus, OH, United States
                [11] 11Department of Microbial Infection and Immunity, The Ohio State University , Columbus, OH, United States
                [12] 12Department of Biology, University of Nevada, Reno , Reno, NV, United States
                [13] 13Department of Biostatistics, Virginia Commonwealth University , Richmond, VA, United States
                [14] 14Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University , Portland, OR, United States
                [15] 15Department of Obstetrics and Gynecology, Oregon Health & Science University , Portland, OR, United States
                [16] 16Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego , San Diego, CA, United States
                [17] 17Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA, United States
                [18] 18Department of Electrical and Computer Engineering, The University of Iowa , Iowa City, IA, United States
                [19] 19Department of Dermatology, The University of Iowa , Iowa City, IA, United States
                Author notes

                Edited by: Rachel Susan Poretsky, The University of Illinois at Chicago, United States

                Reviewed by: Ram Prasad, Mahatma Gandhi Central University, Motihari, India; Emily K. Cope, Northern Arizona University, United States

                This article was submitted to Systems Microbiology, a section of the journal Frontiers in Microbiology

                Article
                10.3389/fmicb.2020.00136
                7042322
                32140140
                cc113ccf-309d-4fe2-8683-e3d2d17d360d
                Copyright © 2020 Cullen, Aneja, Beyhan, Cho, Woloszynek, Convertino, McCoy, Zhang, Anderson, Alvarez-Ponce, Smirnova, Karstens, Dorrestein, Li, Sen Gupta, Cheung, Powers, Zhao and Rosen.

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

                History
                : 13 August 2019
                : 21 January 2020
                Page count
                Figures: 4, Tables: 0, Equations: 1, References: 265, Pages: 27, Words: 0
                Categories
                Microbiology
                Review

                Microbiology & Virology
                microbiome interactions,gut microbiome,skin microbiome,prebiotics,probiotics,microbiome evolution,microbiome ecology,microbial forensics

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