Multidisciplinarity in Microbiome Research: A Challenge and Opportunity to Rethink Causation,Variability, and Scale

This essay, written by a biologist, a microbial ecologist, a biological anthropologist, and an anthropologist‐historian, examines tensions and translations in microbiome research on animals in the laboratory and field. The authors trace how research questions and findings in the laboratory are extrapolated into the field and vice versa, and the shifting evidentiary standards that these research settings require. Showing how complexities of microbiomes challenge traditional standards of causation, the authors contend that these challenges require new approaches to inferences used in ecology, anthropology, and history. As social scientists incorporate investigations of microbial life into their human studies, microbiome researchers venture into field settings to develop mechanistic understandings about the functions of complex microbial communities. These efforts generate new possibilities for cross‐fertilizations and inference frameworks to interpret microbiome findings. Microbiome research should integrate multiple scales, levels of variability, and other disciplinary approaches to tackle questions spanning conditions from the laboratory to the field.     

Neutral Models of Microbiome Evolution

There has been an explosion of research on host-associated microbial communities (i.e.,microbiomes). Much of this research has focused on surveys of microbial diversities across a variety of host species, including humans, with a view to understanding how these microbiomes are distributed across space and time, and how they correlate with host health, disease, phenotype, physiology and ecology. Fewer studies have focused on how these microbiomes may have evolved. In this paper, we develop an agent-based framework to study the dynamics of microbiome evolution. Our framework incorporates neutral models of how hosts acquire their microbiomes, and how the environmental microbial community that is available to the hosts is assembled. Most importantly, our framework also incorporates a Wright-Fisher genealogical model of hosts, so that the dynamics of microbiome evolution is studied on an evolutionary timescale. Our results indicate that the extent of parental contribution to microbial availability from one generation to the next significantly impacts the diversity of microbiomes: the greater the parental contribution, the less diverse the microbiomes. In contrast, even when there is only a very small contribution from a constant environmental pool, microbial communities can remain highly diverse. Finally, we show that our models may be used to construct hypotheses about the types of processes that operate to assemble microbiomes over evolutionary time.     

Colliding and interacting microbiomes and microbial communities - consequences for human health

Living ‘things’ coexist with microorganisms, known as the microbiota/microbiome that provides essential physiological functions to its host. Despite this reliance, the microbiome is malleable and can be altered by several factors including birth-mode, age, antibiotics, nutrition, and disease. In this minireview, we consider how other microbiomes and microbial communities impact the host microbiome and the host through the concept of microbiome collisions (initial exposures) and interactions. Interactions include changes in host microbiome composition and functionality and/or host responses. Understanding the impact of other microbiomes and microbial communities on the microbiome and host are important considering the decline in human microbiota diversity in the developed world – paralleled by the surge of non-communicable, inflammatory-based diseases. Thus, surrounding ourselves with rich and diverse beneficial microbiomes and microbial communities to collide and interact with should help to diminish the loss in microbial diversity and protect from certain diseases. In the same vein, our microbiomes not only influence our health but potentially the health of those close to us. We also consider strategies for enhanced host microbiome collisions and interactions through the surrounding environment that ensure increased microbiome diversity and functionality contributing to enhanced symbiotic return to the host in terms of health benefit.     

Metacommunity theory for transmission of heritable symbionts within insect communities

Microbial organisms are ubiquitous in nature and often form communities closely associated with their host, referred to as the microbiome. The microbiome has strong influence on species interactions, but microbiome studies rarely take interactions between hosts into account, and network interaction studies rarely consider microbiomes. Here, we propose to use metacommunity theory as a framework to unify research on microbiomes and host communities by considering host insects and their microbes as discretely defined “communities of communities” linked by dispersal (transmission) through biotic interactions. We provide an overview of the effects of heritable symbiotic bacteria on their insect hosts and how those effects subsequently influence host interactions, thereby altering the host community. We suggest multiple scenarios for integrating the microbiome into metacommunity ecology and demonstrate ways in which to employ and parameterize models of symbiont transmission to quantitatively assess metacommunity processes in host‐associated microbial systems. Successfully incorporating microbiota into community‐level studies is a crucial step for understanding the importance of the microbiome to host species and their interactions.     

Environmental stress destabilizes microbial networks

Environmental stress is increasing worldwide, yet we lack a clear picture of how stress disrupts the stability of microbial communities and the ecosystem services they provide. Here, we present the first evidence that naturally-occurring microbiomes display network properties characteristic of unstable communities when under persistent stress. By assessing changes in diversity and structure of soil microbiomes along 40 replicate stress gradients (elevation/water availability gradients) in the Florida scrub ecosystem, we show that: (1) prokaryotic and fungal diversity decline in high stress, and (2) two network properties of stable microbial communities—modularity and negative:positive cohesion—have a clear negative relationship with environmental stress, explaining 51–78% of their variation. Interestingly, pathogenic taxa/functional guilds decreased in relative abundance along the stress gradient, while oligotrophs and mutualists increased, suggesting that the shift in negative:positive cohesion could result from decreasing negative:positive biotic interactions consistent with the predictions of the Stress Gradient Hypothesis. Given the crucial role microbiomes play in ecosystem functions, our results suggest that, by limiting the compartmentalization of microbial associations and creating communities dominated by positive associations, increasing stress in the Anthropocene could destabilize microbiomes and undermine their ecosystem services.Subject terms: Microbial ecology, Microbial ecology     

Functional metagenomics: a tool to gain knowledge for agronomic and veterinary sciences

The increased global demand for food production has motivated agroindustries to increase their own levels of production. Scientific efforts have contributed to improving these production systems, aiding to solve problems and establishing novel conceptual views and sustainable alternatives to cope with the increasing demand. Although microorganisms are key players in biological systems and may drive certain desired responses toward food production, little is known about the microbial communities that constitute the microbiomes associated with agricultural and veterinary activities. Understanding the diversity, structure and in situ interactions of microbes, together with how these interactions occur within microbial communities and with respect to their environments (including hosts), constitutes a major challenge with an enormous relevance for agriculture and biotechnology. The emergence of high-throughput sequencing technologies, together with novel and more accessible bioinformatics tools, has allowed researchers to learn more about the functional potential and functional activity of these microbial communities. These tools constitute a relevant approach for understanding the metabolic processes that can occur or are currently occurring in a given system and for implementing novel strategies focused on solving production problems or improving sustainability. Several ‘omics’ sciences and their applications in agriculture are discussed in this review, and the usage of functional metagenomics is proposed to achieve substantial advances for food agroindustries and veterinary sciences.     

Microbial communities involved in enhanced biological phosphorus removal from wastewater--a model system in environmental biotechnology

Enhanced biological phosphorus removal (EBPR) is one of the most advanced and complicated wastewater treatment processes applied today, and it is becoming increasingly popular worldwide as a sustainable way to remove and potentially reuse P. It is carried out by complex microbial communities consisting primarily of uncultured microorganisms. The EBPR process is a well-studied system with clearly defined boundaries which makes it very suitable as a model ecosystem in microbial ecology. Of particular importance are the transformations of C, N, and P, the solid-liquid separation properties and the functional and structural stability. A range of modern molecular methods has been used to study these communities in great detail including single cell microbiology, various -omics methods, flux analyses, and modeling making this one of the best studied microbial ecosystems so far. Recently, an EBPR core microbiome has been described and we present in this article some highlights and show how this complex microbial community can be used as model ecosystem in environmental biotechnology.     

Q&A: Friends (but sometimes foes) within: the complex evolutionary ecology of symbioses between host and microbes

Over the past decade, there has been a pronounced shift in the study of host–microbe associations, with recognition that many of these associations are beneficial, and often critical, for a diverse array of hosts. There may also be pronounced benefits for the microbes, though this is less well empirically understood. Significant progress has been made in understanding how ecology and evolution shape simple associations between hosts and one or a few microbial species, and this work can serve as a foundation to study the ecology and evolution of host associations with their often complex microbial communities (microbiomes).     

Next-generation approaches to the microbial ecology of food fermentations

Food fermentations have enhanced human health since the dawn of time and remain a prevalent means of food processing and preservation. Due to their cultural and nutritional importance, many of these foods have been studied in detail using molecular tools, leading to enhancements in quality and safety. Furthermore, recent advances in high-throughput sequencing technology are revolutionizing the study of food microbial ecology, deepening insight into complex fermentation systems. This review provides insight into novel applications of select molecular techniques, particularly next-generation sequencing technology, for analysis of microbial communities in fermented foods. We present a guideline for integrated molecular analysis of food microbial ecology and a starting point for implementing next-generation analysis of food systems.     

Population level virulence in polymicrobial communities associated with chronic disease

Renewed studies of chronic infection have shifted the focus from single pathogens to multi-microbial communities as culture-independent techniques reveal complex consortia of microbes associated with c...     

Microbial diversity-productivity relationships in aquatic ecosystems

Thanks to recent advances in molecular biology, one's knowledge of microbial co-occurrence patterns, microbial biogeography and microbial biodiversity is expanding rapidly. This MiniReview explores microbial diversity-productivity relationships in the light of what is known from the general ecology literature. Analyses of microbial diversity-productivity relationships from 70 natural, experimental, and engineered aquatic ecosystems reveal patterns that are strikingly similar to those that have long been documented for communities of macroorganisms. Microbial ecology and the general science of ecology are thus continuing to converge.     

Stochasticity in microbiology: managing unpredictability to reach the Sustainable Development Goals

Pure (single) cultures of microorganisms and mixed microbial communities (microbiomes) have been important for centuries in providing renewable energy, clean water and food products to human society and will continue to play a crucial role to pursue the Sustainable Development Goals. To use microorganisms effectively, microbial engineered processes require adequate control. Microbial communities are shaped by manageable deterministic processes, but also by stochastic processes, which can promote unforeseeable variations and adaptations. Here, we highlight the impact of stochasticity in single culture and microbiome engineering. First, we discuss the concepts and mechanisms of stochasticity in relation to microbial ecology of single cultures and microbiomes. Second, we discuss the consequences of stochasticity in relation to process performance and human health, which are reflected in key disadvantages and important opportunities. Third, we propose a suitable decision tool to deal with stochasticity in which monitoring of stochasticity and setting the boundaries of stochasticity by regulators are central aspects. Stochasticity may give rise to some risks, such as the presence of pathogens in microbiomes. We argue here that by taking the necessary precautions and through clever monitoring and interpretation, these risks can be mitigated.     

微生物分子生态学技术在污水处理系统中的应用

微生物分子生态学作为分子生物学与微生物生态学交叉而形成的学科,在污水处理方面广泛应用。本文从分子生态学实验技术角度,综述了目前污水处理系统中微生物群体结构、多样性及其与功能相关性的研究进展,探讨了分子生态学技术的发展与应用前景,并指出研究该体系微生物对于认识微生物系统发育地位具有重要意义。     

Key players and team play: anaerobic microbial communities in hydrocarbon-contaminated aquifers

Biodegradation of anthropogenic pollutants in shallow aquifers is an important microbial ecosystem service which is mainly brought about by indigenous anaerobic microorganisms. For the management of contaminated sites, risk assessment and control of natural attenuation, the assessment of in situ biodegradation and the underlying microbial processes is essential. The development of novel molecular methods, “omics” approaches, and high-throughput techniques has revealed new insight into complex microbial communities and their functions in anoxic environmental systems. This review summarizes recent advances in the application of molecular methods to study anaerobic microbial communities in contaminated terrestrial subsurface ecosystems. We focus on current approaches to analyze composition, dynamics, and functional diversity of subsurface communities, to link identity to activity and metabolic function, and to identify the ecophysiological role of not yet cultured microbes and syntrophic consortia. We discuss recent molecular surveys of contaminated sites from an ecological viewpoint regarding degrader ecotypes, abiotic factors shaping anaerobic communities, and biotic interactions underpinning the importance of microbial cooperation for microbial ecosystem services such as contaminant degradation.     

FISH技术在微生物生态学中的研究及进展

分子生物学技术在微生物生态学研究中具有灵敏、精确和快速的优势,但不能提供微生物的形态学、数量性状、空间分布等信息。荧光原位杂交技术结合了分子生物学的精确性和显微镜的可视性信息,可以在自然生境中监测和鉴定不同的微生物个体,尤其是对难培养和未被培养的微生物进行检测。荧光原位杂交技术被广泛用于微生物群落结构诊断和评价,现已成为微生物分子生态学研究中的热点技术。对荧光原位杂交技术的发展和在微生物分子生态学中的应用进行了综述,探讨了该技术应用中存在的问题和发展前景。     

Ecosystems biology of microbial metabolism

The metabolic capabilities of many environmentally and medically important microbes can be quantitatively explored using systems biology approaches to metabolic networks. Yet, as we learn more about the complex microbe-microbe and microbe-environment interactions in microbial communities, it is important to understand whether and how system-level approaches can be extended to the ecosystem level. Here we summarize recent work that addresses these challenges at multiple scales, starting from two-species natural and synthetic ecology models, up to biosphere-level approaches. Among the many fascinating open challenges in this field is whether the integration of high throughput sequencing methods and mathematical models will help us capture emerging principles of ecosystem-level metabolic organization and evolution.     

Oral microbiomes: more and more importance in oral cavity and whole body

Microbes appear in every corner of human life, and microbes affect every aspect of human life. The human oral cavity contains a number of different habitats. Synergy and interaction of variable oral microorganisms help human body against invasion of undesirable stimulation outside. However, imbalance of microbial flora contributes to oral diseases and systemic diseases. Oral microbiomes play an important role in the human microbial community and human health. The use of recently developed molecular methods has greatly expanded our knowledge of the composition and function of the oral microbiome in health and disease. Studies in oral microbiomes and their interactions with microbiomes in variable body sites and variable health condition are critical in our cognition of our body and how to make effect on human health improvement.     

Microbial diversity and function in soil: from genes to ecosystems

Soils sustain an immense diversity of microbes, which, to a large extent, remains unexplored. A range of novel methods, most of which are based on rRNA and rDNA analyses, have uncovered part of the soil microbial diversity. The next step in the era of microbial ecology is to extract genomic, evolutionary and functional information from bacterial artificial chromosome libraries of the soil community genomes (the metagenome). Sophisticated analyses that apply molecular phylogenetics, DNA microarrays, functional genomics and in situ activity measurements will provide huge amounts of new data, potentially increasing our understanding of the structure and function of soil microbial ecosystems, and the interactions that occur within them. This review summarizes the recent progress in studies of soil microbial communities with focus on novel methods and approaches that provide new insight into the relationship between phylogenetic and functional diversity.     

Microbial communities are indicators of parasite infection status

Growing evidence suggests that microbiomes have been shaping the evolutionary pathways of macroorganisms for millennia and that these tiny symbionts can influence, and possibly even control, species interactions like host–parasite relationships. Yet, while studies have investigated host–parasites and microbiomes separately, little has been done to understand all three groups synergistically. Here, we collected infected and uninfected Eurypanopeus depressus crab hosts from a coastal North Carolina oyster reef three times over 4 months. Infected crabs demonstrated an external stage of the rhizocephalan parasite, Loxothylacus panopaei. Community analyses revealed that microbial richness and diversity were significantly different among tissue types (uninfected crab, infected crab, parasite externae and parasite larvae) and over time (summer and fall). Specifically, the microbial communities from parasite externae and larvae had similar microbiomes that were consistent through time. Infected crabs demonstrated microbial communities spanning those of their host and parasite, while uninfected crabs showed more distinctive communities with greater variability over time. Microbial communities were also found to be indicators of early-stage infections. Resolving the microbial community composition of a host and its parasite is an important step in understanding the microbiome's role in the host–parasite relationship and determining how this tripartite relationship impacts coevolutionary processes.     

Where Next for Microbiome Research?

The development of high-throughput sequencing technologies has transformed our capacity to investigate the composition and dynamics of the microbial communities that populate diverse habitats. Over the past decade, these advances have yielded an avalanche of metagenomic data. The current stage of “van Leeuwenhoek”–like cataloguing, as well as functional analyses, will likely accelerate as DNA and RNA sequencing, plus protein and metabolic profiling capacities and computational tools, continue to improve. However, it is time to consider: what’s next for microbiome research? The short pieces included here briefly consider the challenges and opportunities awaiting microbiome research.

This Perspective is part of the “Where next?” Series.

Soon, we will enter an era when “the number of population genomes deposited in public databases will dwarf those from isolates and single cells” (Gene Tyson). Clearly, as all authors noted in the following, our focus will move from describing the composition of microbial communities to elucidating the principles that govern their assembly, dynamics, and functions. How will such principles be discovered? Elhanan Borenstein proposes that a systems biology–based approach, particularly the development of mathematical and computational models of the interactions between the specific community components, will be critical for understanding the function and dynamics of microbiomes. Evolutionary biologists Howard Ochman and Andrew Moeller want to decipher how microbial assemblies evolve but challenge us to also consider the role of microbial communities in organismal evolution, and they make the exciting prediction that microbes will be implicated in the evolution of eusociality and cooperation. Brett Finlay underscores the need for deciphering the mechanistic bases—particularly the chemical/metabolite signals—for interactions between members of microbial communities and their hosts. He emphasizes how this knowledge will enable creation of new tools to manipulate the microbiota, a key challenge for future investigation. Heidi Kong also encourages deciphering the mechanisms that underlie associations between particular skin surfaces and disorders and their respective microbiota. Jeffrey Gordon considers several intriguing opportunities as well as challenges that manipulation of the gut microbiota presents for improved human nutrition and health. Finally, Karen Nelson, Karim Dabbagh and Hamilton Smith suggest that using synthetic genomes to create novel microbes or even synthetic microbiomes offers a new way to engineer the microbiota. Overall, future microbiome research regarding the molecules and mechanisms mediating interactions between members of microbial communities and their hosts should lead to discovery of exciting new biology and transformative therapeutics.