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1. Gut Microbiome: Profound Implications for Diet and Disease

   https://doi.org/10.3390/nu11071613  

   Hills, Ronald D.; Pontefract, Benjamin A.; Mishcon, Hillary R.; Black, Cody A.; Sutton, Steven C.; Theberge, Cory R. (July 2019, Nutrients)

   The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease. 

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2. Engineered calprotectin-sensing probiotics for IBD surveillance in humans

   https://doi.org/10.1073/pnas.2221121120  

   Xia, Jonathan Y; Hepler, Chelsea; Tran, Peter; Waldeck, Nathan J; Bass, Joseph; Prindle, Arthur (August 2023, Proceedings of the National Academy of Sciences)

   Inflammatory bowel disease (IBD) is a spectrum of autoimmune diseases affecting the gastrointestinal tract characterized by a relapsing and remitting course of gut mucosal inflammation. Disease flares can be difficult to predict, and the current practice of IBD disease activity surveillance through endoscopy is invasive and requires medical expertise. Recent advancements in synthetic biology raise the possibility that symbiotic microbes can be engineered to selectively detect disease biomarkers used in current clinical practice. Here, we introduce an engineered probiotic capable of detecting the clinical gold standard IBD biomarker, calprotectin, with sensitivity and specificity in IBD patients. Specifically, we identified a bacterial promoter in the probiotic strainEscherichia coliNissle 1917 (EcN) which exhibits a specific expression increase in the presence of calprotectin. Using murine models of colitis, we show that the reporter signal is activated in vivo during transit of the GI tract following oral delivery. Furthermore, our engineered probiotic can successfully discriminate human patients with active IBD from those in remission and without IBD using patient stool samples, where the intensity of reporter signal quantitatively tracks with clinical laboratory–measured levels of calprotectin. Our pilot study sets the stage for probiotics that can be engineered to detect fecal calprotectin for precise noninvasive disease activity monitoring in IBD patients. 

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3. Plant Genetics as a Tool for Manipulating Crop Microbiomes: Opportunities and Challenges

   https://doi.org/10.3389/fbioe.2021.567548  

   Clouse, Kayla M.; Wagner, Maggie R. (May 2021, Frontiers in Bioengineering and Biotechnology)

   Growing human population size and the ongoing climate crisis create an urgent need for new tools for sustainable agriculture. Because microbiomes have profound effects on host health, interest in methods of manipulating agricultural microbiomes is growing rapidly. Currently, the most common method of microbiome manipulation is inoculation of beneficial organisms or engineered communities; however, these methods have been met with limited success due to the difficulty of establishment in complex farm environments. Here we propose genetic manipulation of the host plant as another avenue through which microbiomes could be manipulated. We discuss how domestication and modern breeding have shaped crop microbiomes, as well as the potential for improving plant-microbiome interactions through conventional breeding or genetic engineering. We summarize the current state of knowledge on host genetic control of plant microbiomes, as well as the key challenges that remain. 

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4. The role of the microbiome in human disease

   Flowers, L. (February 2023, Biomedical journal of scientific technical research)

   Since the invention of the microscope, scientists have described microbial communities on living and non-living matter. In terms of human-associated microbes, scientists have documented the beneficial effects of the microbiota for many decades. Prophylactic effects include protection from pathogens, digestion potential, and the production of essential vitamins. However, recent high-throughput methodologies and analytical advances have accelerated microbiome science and our understanding of microbial diversity in living organisms. The microbiome denotes the complex network of all the microorganisms and microbial genes located in specific biotic or abiotic environments. We now realize the enormous diversity and functionality of the microbiota in humans and the endless benefits to health and disease. Dysbiosis facilitates the manufacture of various proinflammatory mediators, biochemical imbalances, and colonization of microbes associated with disease outcomes. Additional work is necessary to determine whether changes in the human microbiome are due to anthropogenic, genetic, or environmental variations. This review will present microbiome research studies focusing on human disease. The findings documented in this article offer optimism on the profound role microorganisms play in supporting human health and how pharmaceutical interactions targeting specific microbes can decrease the incidence of human disease caused by the ecological disturbance of the normal microbiota. 

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5. Opening up "containment": Technological and social dimensions of biocontainment for genetically engineered organisms designed for deliberate release

   https://doi.org/10.22541/au.174526562.21903148/v1  

   George, Dalton; Brewer, Avery; Dale, Anna; Danciu, Mark; Isabelle, Casey; Frow, Emma (April 2025, Authorea Inc.)

   Advances in engineering biology, together with growing interest and investment in supporting a bio-based economy in the US, are fueling research and development efforts into genetically engineering organisms for all kinds of different applications. While many of these applications involve using genetically engineered microorganisms in contained, bioreactor-like environments, there is also increasing interest in designing organisms (microbes, plants, insects, animals) for release and deployment in the open environments. This includes genetically modified crops, as well as direct-to-consumer probiotics and organisms designed for environmental remediation. Historically, examples of genetically engineered organisms released in open environments in the US remain limited, aside from GM crops. Industry enthusiasm for releasing genetically engineered microorganisms in particular waned at least partly in response to public controversy surrounding the field testing of Frostban “ice-minus” bacteria on strawberry crops in 1987. Development of living engineered products, together with publicly funded research on environmental transport and fate of engineered microorganisms in open environments, stalled. As a result, our approach to managing engineered microorganisms over the past 40 years has largely defaulted to the biosafety framework for genetic engineering in laboratory contexts, which emerged from the storied 1975 Asilomar meeting. This biosafety framework focuses on technological containment, a framing that prioritizes separation between genetically engineered organisms and the wider world. In this report, we argue that technological containment is insufficient for robust discussion and evaluation of genetically engineered organisms in open, complex environments. We introduce and make the case for a broader lens—which we call social containment—to be included alongside discussions of technological containment. Social containment directs our attention to how the cultural, environmental and political context around a genetically engineered organism (the sociotechnical system) is held together or challenged through its development and commercialization process. In this report, we use the lens of social containment to tell the stories of 11 genetically engineered organisms designed for deliberate release in the US. The cases cover historical and contemporary examples, genetically engineered microbes, plants and animals, and different application contexts. Through these stories, we show how technological, social, economic, legal, spatiotemporal and environmental considerations interact to smooth or disrupt the development process. We argue that this more holistic approach to understanding the relationships between genetically engineered organisms and the world is important in the context of recent, renewed interest in pursuing deliberate release applications. High-level findings emerging across the case studies include: 1) Development and commercialization pathways can look very different across genetically engineered organisms. There isn’t one, single factor that systematically emerges as the most important in determining the fate of a product. Some products have faced significant disruption in their developmental trajectories from different combinations of factors, while others have been more smoothly managed. Across the case studies, we identify factors that can work together to enable or constrain product trajectories. 2) The presence or absence of explicit, technological biocontainment strategies is not a reliable indicator of a successful product. Arguably, the absence of engineered biocontainment has resulted in more successful commercializations across our case studies than products with genetic biocontainment strategies engineered into them. 3) Public and stakeholder views on genetically engineered organisms are highly context-specific. We observe that public trust varies substantially across the case studies in this report, and should not necessarily be seen as a disruptive factor. Sensitivity to existing cultural norms and power dynamics is a key part of successful product development. Through this set of stories, we hope to open up ways for researchers and policy practitioners to think about containment as more than a simple technological concern. We encourage others to use our proposed framework to study their own genetically engineered organisms of interest—historical or contemporary, US-based or international—and we invite reflection on the variety of technological AND social processes by which genetically engineered organisms are controlled and managed in our society. 

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