Sick Individuals and Sick (Microbial) Populations: Challenges in Epidemiology and the Microbiome

The human microbiome represents a new frontier in understanding the biology of human health. While epidemiology in this area is still in its infancy, its scope will likely expand dramatically over the coming years. To rise to the challenge, we argue that epidemiology should capitalize on its population perspective as a critical complement to molecular microbiome research, allowing for the illumination of contextual mechanisms that may vary more across populations rather than among individuals. We first briefly review current research on social context and the gut microbiome, focusing specifically on socioeconomic status (SES) and race/ethnicity. Next, we reflect on the current state of microbiome epidemiology through the lens of one specific area, the association of the gut microbiome and metabolic disorders. We identify key methodological shortcomings of current epidemiological research in this area, including extensive selection bias, the use of noncompositionally robust measures, and a lack of attention to social factors as confounders or effect modifiers.

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Gut Feeling

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1860 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S504-S505

Author(s):

C. Cotta ◽

G. Jesus ◽

V. Vila Nova ◽

C. Moreira

Keyword(s):

Mental Disorders ◽

Gut Microbiota ◽

Gut Microbiome ◽

Bacterial Infections ◽

Human Microbiome ◽

Dietary Interventions ◽

Scientific Databases ◽

Antibiotic Drugs ◽

Microbiome Research ◽

Competing Interest

IntroductionThere is growing evidence of the importance of nutrition in mental disorders. Gut microbiota, influenced by environmental factors such as diet and stress, has been proposed as one of the players on a dynamic called gut-brain axis, which is thought to have an influence on behaviour and mental health.Objectives and aimsTo summarize recent evidence on the topic, and its potential role in psychiatric interventions.MethodsThe authors review updated literature collected from online scientific databases.ResultsThe development of the brain itself has been shown to be influenced by the gut microbiome. Research demonstrates that the composition of the microbiota has influence on behaviour through neuroendocrine and other neuroactive messengers production by the bacteria within the gut lumen. Studies in germ-free animals, animals exposed to bacterial infections, probiotic suplements or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. The gut microbiome has been implicated in brain disorders including anxiety and depression, multiple sclerosis, Alzheimer's disease, Parkinson's disease, and autism.ConclusionsThe treatment of mental disorders is usually based on pharmacological and psychotherapeutic interventions, and little attention is given to dietary interventions. The emerging field of research focused on the human microbiome suggests an important role for the gut microbiota in influencing brain development, behaviour and mood in humans, and points new strategies for developing novel therapeutics for mental disorders.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Rethinking antimicrobial stewardship paradigms in the context of the gut microbiome

JAC-Antimicrobial Resistance ◽

10.1093/jacamr/dlz015 ◽

2019 ◽

Vol 1 (1) ◽

Cited By ~ 1

Author(s):

Farah Shahi ◽

Kelly Redeker ◽

James Chong

Keyword(s):

Gut Microbiome ◽

Human Microbiome ◽

Health Impacts ◽

Current Evidence ◽

Gram Negative Bacteria ◽

Human Gut ◽

Routes Of Administration ◽

Health And Disease ◽

Diverse Community ◽

Review Current

Abstract Ongoing concerns over the presence and persistence of antimicrobial resistance (AMR), particularly in Gram-negative bacteria, continue to have significant global health impacts. The gastrointestinal tract, or ‘gut’, environment amplifies AMR in the human gut microbiome, even in the absence of antibiotics. It constitutes a complex and diverse community of organisms, and patterns and alterations within it are increasingly being found to be associated with states of health and disease. Our understanding of the effects of routes of administration of antimicrobials on the gut microbiome is still lacking despite recent advances in metagenomics. In this article we review current evidence for antibiotic effects on gut microbiota and explore possible prescribing and stewardship approaches that would seek to minimize these effects. If we are to preserve existing and new antimicrobials, we need to consider their use in the context of their effect on gut ecology, and the human microbiome in general.

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The current state and future direction of DoD gut microbiome research: a summary of the first DoD gut microbiome informational meeting

Standards in Genomic Sciences ◽

10.1186/s40793-018-0308-0 ◽

2018 ◽

Vol 13 (1) ◽

Cited By ~ 7

Author(s):

Steven Arcidiacono ◽

Jason W. Soares ◽

J. Philip Karl ◽

Linda Chrisey ◽

C. P. T. Blair C. R. Dancy ◽

...

Keyword(s):

Gut Microbiome ◽

Current State ◽

Microbiome Research ◽

Future Direction

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Workshop report: Toward the development of a human whole stool reference material for metabolomic and metagenomic gut microbiome measurements

Metabolomics ◽

10.1007/s11306-020-01744-5 ◽

2020 ◽

Vol 16 (11) ◽

Author(s):

Rupasri Mandal ◽

Raul Cano ◽

Cindy D. Davis ◽

David Hayashi ◽

Scott A. Jackson ◽

...

Keyword(s):

Quality Control ◽

Reference Material ◽

North America ◽

Gut Microbiome ◽

Community Needs ◽

The North ◽

Current State ◽

Course Of Action ◽

Microbiome Research ◽

The Impact

Abstract Introduction To date, there has been little effort to develop standards for metabolome-based gut microbiome measurements despite the significant efforts toward standard development for DNA-based microbiome measurements. Objectives The National Institute of Standards and Technology (NIST), The BioCollective (TBC), and the North America Branch of the International Life Sciences Institute (ILSI North America) are collaborating to extend NIST’s efforts to develop a Human Whole Stool Reference Material for the purpose of method harmonization and eventual quality control. Methods The reference material will be rationally designed for adequate quality assurance and quality control (QA/QC) for underlying measurements in the study of the impact of diet and nutrition on functional aspects of the host gut microbiome and relationships of those functions to health. To identify which metabolites deserve priority in their value assignment, NIST, TBC, and ILSI North America jointly conducted a workshop on September 12, 2019 at the NIST campus in Gaithersburg, Maryland. The objective of the workshop was to identify metabolites for which evidence indicates relevance to health and disease and to decide on the appropriate course of action to develop a fit-for-purpose reference material. Results This document represents the consensus opinions of workshop participants and co-authors of this manuscript, and provides additional supporting information. In addition to developing general criteria for metabolite selection and a preliminary list of proposed metabolites, this paper describes some of the strengths and limitations of this initiative given the current state of microbiome research. Conclusions Given the rapidly evolving nature of gut microbiome science and the current state of knowledge, an RM (as opposed to a CRM) measured for multiple metabolites is appropriate at this stage. As the science evolves, the RM can evolve to match the needs of the research community. Ultimately, the stool RM may exist in sequential versions. Beneficial to this evolution will be a clear line of communication between NIST and the stakeholder community to ensure alignment with current scientific understanding and community needs.

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The Human Gut Phageome: Origins and Roles in the Human Gut Microbiome

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.643214 ◽

2021 ◽

Vol 11 ◽

Author(s):

Eleanor M. Townsend ◽

Lucy Kelly ◽

George Muscatt ◽

Joshua D. Box ◽

Nicole Hargraves ◽

...

Keyword(s):

Gut Microbiome ◽

Adult Life ◽

Microbial Populations ◽

Human Gut ◽

Bacterial Populations ◽

Human Gut Microbiome ◽

Microbiome Research ◽

Health And Disease ◽

Over Time

The investigation of the microbial populations of the human body, known as the microbiome, has led to a revolutionary field of science, and understanding of its impacts on human development and health. The majority of microbiome research to date has focussed on bacteria and other kingdoms of life, such as fungi. Trailing behind these is the interrogation of the gut viruses, specifically the phageome. Bacteriophages, viruses that infect bacterial hosts, are known to dictate the dynamics and diversity of bacterial populations in a number of ecosystems. However, the phageome of the human gut, while of apparent importance, remains an area of many unknowns. In this paper we discuss the role of bacteriophages within the human gut microbiome. We examine the methods used to study bacteriophage populations, how this evolved over time and what we now understand about the phageome. We review the phageome development in infancy, and factors that may influence phage populations in adult life. The role and action of the phageome is then discussed at both a biological-level, and in the broader context of human health and disease.

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Associations Between Dysmenorrhea Symptom-Based Phenotypes and Vaginal Microbiome: A Pilot Study

Biological Research For Nursing ◽

10.1177/1099800420979606 ◽

2020 ◽

pp. 109980042097960

Author(s):

Chen X. Chen ◽

Janet S. Carpenter ◽

Tabitha Murphy ◽

Patricia Brooks ◽

J. Dennis Fortenberry

Keyword(s):

Young Adults ◽

Gut Microbiome ◽

Treatment Options ◽

Human Microbiome ◽

16S Rrna Gene Sequencing ◽

Adolescents And Young Adults ◽

Rrna Gene ◽

Sample Collection ◽

Microbiome Research ◽

Prospective Longitudinal

Human microbiome research provides rich opportunities to elucidate factors influencing health, uncover novel biomarkers, and expand disease treatment options. A well-conducted microbiome study depends not only on a rigorous design but also on successfully engaging participants in collecting quality samples. In this paper, we aim to describe (1) strategies our team used to engage adolescents and young adults in vaginal and gut microbiome sample self-collection and (2) their effectiveness. In our prospective, longitudinal, feasibility study of 20 female adolescents and young adults, research participants self-collected vaginal and gut microbiome samples at home. Using a participatory and iterative process, we developed strategies to engage participants in sample self-collection, including (1) providing clear instructions to ensure comprehension and buy-in, (2) providing a user-friendly take-home package, (3) minimizing disgust/embarrassment associated with sample collection, and (4) follow-up communications to facilitate sample collections and return. With these strategies, we achieved 100% participant retention and 100% sample return rates. All samples ( n = 80, 100%) were usable for downstream 16s rRNA gene sequencing and analysis. All participants rated the study procedures as acceptable, and qualitative data showed that strategies were well received by participants. This study suggests that carefully planning and implementing strategies to engage participants in sample self-collection can result in high degrees of participant compliance, sample quality, and participant satisfaction in microbiome research.

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Microbial evolution and ecological opportunity in the gut environment

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2019.1964 ◽

2019 ◽

Vol 286 (1915) ◽

pp. 20191964 ◽

Cited By ~ 2

Author(s):

Pauline D. Scanlan

Keyword(s):

Gut Microbiome ◽

Experimental Evolution ◽

Microbial Evolution ◽

Microbial Populations ◽

Human Gut ◽

Ecological Opportunity ◽

Microbiome Research ◽

Functional Consequences ◽

Using Data ◽

Individual Human

Recent genomic and metagenomic studies have highlighted the presence of rapidly evolving microbial populations in the human gut. However, despite the fundamental implications of this intuitive finding for both basic and applied gut microbiome research, very little is known about the mode, tempo and potential functional consequences of microbial evolution in the guts of individual human hosts over a lifetime. Here I assess the potential relevance of ecological opportunity to bacterial adaptation, colonization and persistence in the neonate and germ-free mammalian gut environment as well as over the course of an individual lifetime using data emerging from mouse models as well as human studies to provide examples where possible. I then briefly outline how the continued development and application of experimental evolution approaches coupled to genomic and metagenomic analysis is essential to disentangling drift from selection and identifying specific drivers of evolution in the gut microbiome within and between individual human hosts and populations.

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On the Stability Landscape of the Human Gut Microbiome: Implications for Microbiome-based Therapies

10.1101/176941 ◽

2017 ◽

Author(s):

Travis E. Gibson ◽

Vincent Carey ◽

Amir Bashan ◽

Elizabeth L. Hohmann ◽

Scott T. Weiss ◽

...

Keyword(s):

Gut Microbiome ◽

Fecal Microbiota Transplantation ◽

Human Microbiome ◽

Fecal Microbiota ◽

New Method ◽

Human Gut ◽

Cross Sectional ◽

Human Gut Microbiome ◽

Microbiome Research ◽

The Stability

AbstractUnderstanding how gut microbial species determine their abundances is crucial in developing any microbiome-based therapy. Towards that end, we show that the compositions of our gut microbiota have characteristic and attractive steady states, and hence respond to perturbations in predictable ways. This is achieved by developing a new method to analyze the stability landscape of the human gut microbiome. In order to illustrate the efficacy of our method and its ecological interpretation in terms of asymptotic stability, this novel method is applied to various human cohorts, including large cross-sectional studies, long longitudinal studies with frequent sampling, and perturbation studies via fecal microbiota transplantation, antibiotic and probiotic treatments. These findings will facilitate future ecological modeling efforts in human microbiome research. Moreover, the method allows for the prediction of the compositional shift of the gut microbiome during the fecal microbiota transplantation process. This result holds promise for translational applications, such as, personalized donor selection when performing fecal microbiota transplantations.One Sentence SummaryA new method for analyzing the stability landscape of the human gut microbiome and predicting its steady-state composition is developed.

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A predictive index for health status using species-level gut microbiome profiling

Nature Communications ◽

10.1038/s41467-020-18476-8 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Vinod K. Gupta ◽

Minsuk Kim ◽

Utpal Bakshi ◽

Kevin Y. Cunningham ◽

John M. Davis ◽

...

Keyword(s):

Health Status ◽

Gut Microbiome ◽

Human Microbiome ◽

Diversity Indices ◽

Predictive Index ◽

Α Diversity ◽

Microbiome Research ◽

Microbiome Profiling ◽

Insight Into ◽

Human Stool

Abstract Providing insight into one’s health status from a gut microbiome sample is an important clinical goal in current human microbiome research. Herein, we introduce the Gut Microbiome Health Index (GMHI), a biologically-interpretable mathematical formula for predicting the likelihood of disease independent of the clinical diagnosis. GMHI is formulated upon 50 microbial species associated with healthy gut ecosystems. These species are identified through a multi-study, integrative analysis on 4347 human stool metagenomes from 34 published studies across healthy and 12 different nonhealthy conditions, i.e., disease or abnormal bodyweight. When demonstrated on our population-scale meta-dataset, GMHI is the most robust and consistent predictor of disease presence (or absence) compared to α-diversity indices. Validation on 679 samples from 9 additional studies results in a balanced accuracy of 73.7% in distinguishing healthy from non-healthy groups. Our findings suggest that gut taxonomic signatures can predict health status, and highlight how data sharing efforts can provide broadly applicable discoveries.

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A Novel Index for Predicting Health Status Using Species-level Gut Microbiome Profiling

10.1101/2020.02.24.962100 ◽

2020 ◽

Author(s):

Vinod K. Gupta ◽

Minsuk Kim ◽

Utpal Bakshi ◽

Kevin Y. Cunningham ◽

John M. Davis ◽

...

Keyword(s):

Health Status ◽

Gut Microbiome ◽

General Health ◽

Human Microbiome ◽

Diversity Indices ◽

Gut Health ◽

Microbiome Profile ◽

Α Diversity ◽

Microbiome Research ◽

Species Specific

ABSTRACTThe development of a biologically-interpretable and robust metric that provides clear insight into the general health status (i.e. healthy or non-healthy) of one’s gut microbiome remains an important target in human microbiome research. We introduce the Gut Microbiome Health Index (GMHI), a mathematical formula that determines the degree to which a gut microbiome profile reflects good or adverse health. GMHI was formulated based on microbial species specific to healthy gut ecosystems. These species were identified through a multi-study, integrative analysis on 4,347 human stool metagenomes from 34 published studies across healthy and 12 different disease or abnormal bodyweight conditions. When demonstrated on our population-scale meta-dataset, GMHI is the most robust and consistent predictor of general health compared to α-diversity indices commonly considered as markers for gut health. Validation of GMHI on 679 samples from 9 additional studies resulted in remarkable reproducibility in distinguishing healthy and non-healthy groups. Our findings suggest that gut taxonomic signatures can indeed serve as robust predictors of general health, and highlight the importance of how data sharing efforts can provide broadly-applicable novel discoveries.

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