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At least 19 records

Solutions in microbiome engineering: prioritizing barriers to organism establishment

Abstract Microbiome engineering is increasingly being employed as a solution to challenges in health, agriculture, and climate. Often manipulation involves inoculation of new microbes designed to improve function into a preexisting microbial community. Despite, increased efforts in microbiome engineering inoculants frequently fail to establish and/or confer long-lasting modifications on ecosystem function. We posit that one underlying cause of these shortfalls is the failure to consider barriers to organism establishment. This is a key challenge and focus of macroecology research, specifically invasion biology and restoration ecology. We adopt a framework from invasion biology that summarizes establishment barriers in three categories: (1) propagule pressure, (2) environmental filtering, and (3) biotic interactions factors. We suggest that biotic interactions is the most neglected factor in microbiome engineering research, and we recommend a number of actions to accelerate engineering solutions.

59 BASIC BIOLOGICAL SCIENCES↗

Environmental microbiome engineering for the mitigation of climate change

Abstract Environmental microbiome engineering is emerging as a potential avenue for climate change mitigation. In this process, microbial inocula are introduced to natural microbial communities to tune activities that regulate the long‐term stabilization of carbon in ecosystems. In this review, we outline the process of environmental engineering and synthesize key considerations about ecosystem functions to target, means of sourcing microorganisms, strategies for designing microbial inocula, methods to deliver inocula, and the factors that enable inocula to establish within a resident community and modify an ecosystem function target. Recent work, enabled by high‐throughput technologies and modeling approaches, indicate that microbial inocula designed from the top‐down, particularly through directed evolution, may generally have a higher chance of establishing within existing microbial communities than other historical approaches to microbiome engineering. We address outstanding questions about the determinants of inocula establishment and provide suggestions for further research about the possibilities and challenges of environmental microbiome engineering as a tool to combat climate change.

59 BASIC BIOLOGICAL SCIENCES↗

2024 International Conference on Microbiome Engineering (ICME)

The 2024 International Conference on Microbiome Engineering (ICME) took place November 12-14 at Tufts University in Medford, MA. ICME connects experts from academia and industry to share the most recent developments in the field of microbiome engineering. This includes genetically engineered organisms that function within microbiomes, control of microbiomes through environmental/nutrient modifications, and inference of engineering principles from analysis of synthetic and natural microbiomes. The conference is unique and distinct from other microbiome conferences in that it specifically highlights the integration of engineering design principles with microbiome research (others are more focused on basic biological principles). The conference thus integrates synthetic biology, systems biology, microbial ecology, and bioinformatics across a range of application spaces from the environment to manufacturing, food, and human health. This project utilized support from the Department of Energy’s (DOE) Office of Biological and Environmental Research (BER) to help trainees and early career faculty attend ICME.

60 APPLIED LIFE SCIENCES↗

Integrating Systems and Synthetic Biology to Understand and Engineer Microbiomes

Microbiomes are complex and ubiquitous networks of microorganisms whose seemingly limitless chemical transformations could be harnessed to benefit agriculture, medicine, and biotechnology. Here, the spatial and temporal changes in microbiome composition and function are influenced by a multitude of molecular and ecological factors. This complexity yields both versatility and challenges in designing synthetic microbiomes and perturbing natural microbiomes in controlled, predictable ways. In this review, we describe factors that give rise to emergent spatial and temporal microbiome properties and the meta-omics and computational modeling tools that can be used to understand microbiomes at the cellular and system levels. We also describe strategies for designing and engineering microbiomes to enhance or build novel functions. Throughout the review,we discuss key knowledge and technology gaps for elucidating the networks and deciphering key control points for microbiome engineering, and highlight examples where multiple omics and modeling approaches can be integrated to address these gaps.

42 ENGINEERING↗

Soil microbiome engineering for sustainability in a changing environment

Recent advances in microbial ecology and synthetic biology have the potential to mitigate damage caused by anthropogenic activities that are deleteriously impacting Earth’s soil ecosystems. Here, we discuss challenges and opportunities for harnessing natural and synthetic soil microbial communities, focusing on plant growth promotion under different scenarios. We explore current needs for microbial solutions in soil ecosystems, how these solutions are being developed and applied, and the potential for new biotechnology breakthroughs to tailor and target microbial products for specific applications. We highlight several scientific and technological advances in soil microbiome engineering, including characterization of microbes that impact soil ecosystems, directing how microbes assemble to interact in soil environments, and the developing suite of gene-engineering approaches. This Review underscores the need for an interdisciplinary approach to understand the composition, dynamics and deployment of beneficial soil microbiomes to drive efforts to mitigate or reverse environmental damage by restoring and protecting healthy soil ecosystems.

59 BASIC BIOLOGICAL SCIENCES↗

Protecting honey bees through microbiome engineering

Honey bees are indispensable insects. Their pollination services support modern agriculture and natural ecosystems. Managed honey bee colonies face increasing threats to their survival, ranging from environmental stressors that include agrochemicals to infestations of arthropod pests and infections with microbial pathogens. Like humans, honey bees have a native gut microbiome that supports their health. However, the bee gut microbiome has a simpler composition than the gut microbiome of mammals, and its main constituent bacterial species can be easily cultured outside of the host. Furthermore, this experimental tractability and the need for new methods for protecting hive health have made honey bees a testbed for synthetic microbiomes augmented with probiotic bacteria and engineered DNA. Here, we discuss the natural benefits of bee gut bacteria, recent progress in genetically modifying these bacteria, and how symbiont-mediated RNA interference and other microbiome engineering approaches can boost bee immunity and suppress bee pathogens and parasites. Finally, we discuss how emerging methods for microbiome engineering and biocontainment could be applied to honey bees and used to address challenges in translating these proof-of-principle achievements into safe and effective technologies for field applications at scale.

Biological and medical sciences↗

Microbiome engineering for sustainable agriculture: using synthetic biology to enhance nitrogen metabolism in plant-associated microbes

Plants benefit from symbiotic relationships with their microbiomes. Modifying these microbiomes to further promote plant growth and improve stress tolerance in crops is a promising strategy. However, such efforts have had limited success, perhaps because the original microbiomes quickly re-establish. Since the complex biological networks involved are little understood, progress through conventional means is time-consuming. Synthetic biology, with its practical successes in multiple industries, could speed up this research considerably. Some fascinating candidates for production by synthetic microbiomes are organic nitrogen metabolites and related pyridoxal-5'-phosphate-dependent enzymes, which have pivotal roles in microbe-microbe and plant-microbe interactions. This review summarizes recent studies of these metabolites and enzymes and discusses prospective synthetic biology platforms for sustainable agriculture.

59 BASIC BIOLOGICAL SCIENCES↗

TbasCO: trait-based comparative ‘omics identifies ecosystem-level and niche-differentiating adaptations of an engineered microbiome

A grand challenge in microbial ecology is disentangling the traits of individual populations within complex communities. Various cultivation-independent approaches have been used to infer traits based on the presence of marker genes. However, marker genes are not linked to traits with complete fidelity, nor do they capture important attributes, such as the timing of gene expression or coordination among traits. To address this, we present an approach for assessing the trait landscape of microbial communities by statistically defining a trait attribute as a shared transcriptional pattern across multiple organisms. Leveraging the KEGG pathway database as a trait library and the Enhanced Biological Phosphorus Removal (EBPR) model microbial ecosystem, we demonstrate that a majority (65%) of traits present in 10 or more genomes have niche-differentiating expression attributes. For example, while many genomes containing high-affinity phosphorus transporter pstABCS display a canonical attribute (e.g. up-regulation under phosphorus starvation), we identified another attribute shared by many genomes where transcription was highest under high phosphorus conditions. Taken together, we provide a novel framework for unravelling the functional dynamics of uncultivated microorganisms by assigning trait-attributes through genome-resolved time-series metatranscriptomics.

59 BASIC BIOLOGICAL SCIENCES↗

Advances in engineering algae for biofuel production

While algae demonstrate potential as a sustainable fuel source, low productivities limit the economic realization of algal biofuels. High-throughput strain engineering, omics-informed genome-scale modeling, and microbiome engineering are key technologies for enabling algal biofuels. High-throughput strain engineering efforts generate improved traits, including high biomass productivity and lipid content, in diverse algal species. Genome-scale models, constructed with the aid of omics data, provide insight into metabolic limitations and guide rational algal strain engineering efforts. As outdoor cultivation systems introduce exogenous organisms, microbiome engineering seeks to eliminate harmful organisms and introduce beneficial species. In conclusion, optimizing algal biomass production and lipid content using these technologies may overcome the productivity barrier for the commercialization of algal biofuels.

09 BIOMASS FUELS↗

Integrating microbial communities into algal biotechnology: a pathway to enhanced commercialization

Microalgae are increasingly recognized for their potential in wastewater treatment and the sustainable production of feedstock for fuel, feed, food, and other bioproducts. Like conventional agricultural systems, algal cultivation involves complex microbial communities. However, despite their pivotal role in cultivation outcomes, especially at the commodity-scale, the critical interactions between microalgae and their microbiomes are often overlooked. Here we synthesize current knowledge on the taxonomic diversity, ecological roles, and biotechnological potential of algal microbiomes, with a focus on their interactions with algal hosts through nutrient exchange, growth modulation, pathogen defense, and environmental conditioning. We also examine how environmental factors such as nutrient availability, salinity, and temperature influence these interactions. Advances in microbiome engineering, including synthetic biology and ecological approaches, offer opportunities to enhance beneficial algal-microbiome interactions, thereby improving growth, resilience, and yield. These advancements could lead to more sustainable and economically viable microalgae cultivation, with far-reaching implications for environmental management and biotechnological innovation. By addressing key economic and environmental barriers, microbiome engineering holds transformative potential to revolutionize large-scale algae cultivation and provide sustainable solutions to global challenges.

Microbiology↗

Metabolic complexity drives divergence in microbial communities

Microbial communities are shaped by environmental metabolites, but the principles that govern whether different communities will converge or diverge in any given condition remain unknown, posing fundamental questions about the feasibility of microbiome engineering. Here, in this work, we studied the longitudinal assembly dynamics of a set of natural microbial communities grown in laboratory conditions of increasing metabolic complexity. We found that different microbial communities tend to become similar to each other when grown in metabolically simple conditions, but they diverge in composition as the metabolic complexity of the environment increases, a phenomenon we refer to as the divergence-complexity effect. A comparative analysis of these communities revealed that this divergence is driven by community diversity and by the assortment of specialist taxa capable of degrading complex metabolites. An ecological model of community dynamics indicates that the hierarchical structure of metabolism itself, where complex molecules are enzymatically degraded into progressively simpler ones that then participate in cross-feeding between community members, is necessary and sufficient to recapitulate our experimental observations. In addition to helping understand the role of the environment in community assembly, the divergence-complexity effect can provide insight into which environments support multiple community states, enabling the search for desired ecosystem functions towards microbiome engineering applications.

59 BASIC BIOLOGICAL SCIENCES↗

Engineering Methanogenic Microbiomes to Redirect Flux to Biomass

In this study, we present a method for acquiring and characterizing novel microbial consortia that regulates methanogens and methanotrophs through selective cultivation and metagenomic analysis of indigenous microorganisms in the environment. In addition, we present the work performed as part of this project to model the pathways that act as limiting factors in microbial methane metabolism based on a carbon cycle model. In this report, we describe the methods for selective cultivation of methane-metabolism-related microorganisms from environmental samples, the method for monitoring their methane consumption performance, and the method and results for verifying their functions using quantitative PCR and metagenomics techniques. The microbial consortia containing methanotrophs were obtained through selective cultivation and molecular biological verification, and their methane consumption performance was evaluated. In addition, the potential of the existence of bacteriophages interacting with methane metabolism-related microorganisms was identified through metagenomic sequencing.

09 BIOMASS FUELS↗

Utilizing plant synthetic biology to accelerate plant-microbe interactions research

Plant-microbe interactions are critical to ecosystem resilience and substantially influence crop production. From the perspective of plant science, two important focus areas concerning plant-microbe interactions include: 1) understanding plant molecular mechanisms involved in plant-microbe interfaces and 2) engineering plants for increasing plant disease resistance or enhancing beneficial interactions with microbes to increase their resilience to biotic and abiotic stress conditions. Molecular biology and genetics approaches have been used to investigate the molecular mechanisms underlying plant responses to various beneficial and pathogenic microbes. While these approaches are valuable for elucidating the functions of individual genes and pathways, they fall short of unraveling the complex cross-talk across pathways or systems that plants employ to respond and adapt to environmental stresses. Also, genetic engineering of plants to increase disease resistance or enhance symbiosis with microbes has mainly been attempted or conducted through targeted manipulation of single genes/pathways of plants. Recent advancements in synthetic biology tool development are paving the way for multi-gene characterization and engineering in plants in relation to plant-microbe interactions. Here, we briefly summarize the current understanding of plant molecular pathways involved in plant interactions with beneficial and pathogenic microorganisms. Then, we highlight the progress in applying plant synthetic biology to elucidate the molecular basis of plant responses to microbes, enhance plant disease resistance, engineer synthetic symbiosis, and conduct in situ microbiome engineering. Lastly, we discuss the challenges, opportunities, and future directions for advancing plant-microbe interactions research using the capabilities of plant synthetic biology.

59 BASIC BIOLOGICAL SCIENCES↗

Drivers of stability and transience in composition-functioning links during serial propagation of litter-decomposing microbial communities

ABSTRACT Biotic factors that influence the temporal stability of microbial community functioning are an emerging research focus for the control of natural and engineered systems. The discovery of common features within community ensembles that differ in functional stability over time is a starting point to explore biotic factors. We serially propagated a suite of soil microbial communities through five generations of 28-day microcosm incubations to examine microbial community compositional and functional stability during plant litter decomposition. Using dissolved organic carbon (DOC) abundance as a target function, we hypothesized that microbial diversity, compositional stability, and associated changes in interactions would explain the relative stability of the ecosystem function between generations. Communities with initially high DOC abundance tended to converge towards a “low DOC” phenotype within two generations, but across all microcosms, functional stability between generations was highly variable. By splitting communities into two cohorts based on their relative DOC functional stability, we found that compositional shifts, diversity, and interaction network complexity were associated with the stability of DOC abundance between generations. Further, our results showed that legacy effects were important in determining compositional and functional outcomes, and we identified taxa associated with high DOC abundance. In the context of litter decomposition, achieving functionally stable communities is required to utilize soil microbiomes to increase DOC abundance and long-term terrestrial DOC sequestration as one solution to reduce atmospheric carbon dioxide concentrations. Identifying factors that stabilize function for a community of interest may improve the success of microbiome engineering applications. IMPORTANCE Microbial community functioning can be highly dynamic over time. Identifying and understanding biotic factors that control functional stability is of significant interest for natural and engineered communities alike. Using plant litter–decomposing communities as a model system, this study examined the stability of ecosystem function over time following repeated community transfers. By identifying microbial community features that are associated with stable ecosystem functions, microbial communities can be manipulated in ways that promote the consistency and reliability of the desired function, improving outcomes and increasing the utility of microorganisms.

59 BASIC BIOLOGICAL SCIENCES↗

Association of Diet and Antimicrobial Resistance in Healthy U.S. Adults

Antimicrobial resistance (AMR) represents a significant source of morbidity and mortality worldwide, with expectations that AMR-associated consequences will continue to worsen throughout the coming decades. Since resistance to antibiotics is encoded in the microbiome, interventions aimed at altering the taxonomic composition of the gut might allow us to prophylactically engineer microbiomes that harbor fewer antibiotic resistant genes (ARGs). Diet is one method of intervention, and yet little is known about the association between diet and antimicrobial resistance. To address this knowledge gap, we examined diet using the food frequency questionnaire (FFQ; habitual diet) and 24-h dietary recalls (Automated Self-Administered 24-h [ASA24 ® ] tool) coupled with an analysis of the microbiome using shotgun metagenome sequencing in 290 healthy adult participants of the United States Department of Agriculture (USDA) Nutritional Phenotyping Study. We found that aminoglycosides were the most abundant and prevalent mechanism of AMR in these healthy adults and that aminoglycoside-O-phosphotransferases (aph3-dprime) correlated negatively with total calories and soluble fiber intake. Individuals in the lowest quartile of ARGs (low-ARG) consumed significantly more fiber in their diets than medium- and high-ARG individuals, which was concomitant with increased abundances of obligate anaerobes, especially from the family Clostridiaceae, in their gut microbiota. Finally, we applied machine learning to examine 387 dietary, physiological, and lifestyle features for associations with antimicrobial resistance, finding that increased phylogenetic diversity of diet was associated with low-ARG individuals. These data suggest diet may be a potential method for reducing the burden of AMR.

59 BASIC BIOLOGICAL SCIENCES↗