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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. Connecting gut microbiomes and short chain fatty acids with the serotonergic system and behavior in Gallus gallus and other avian species

   https://doi.org/10.3389/fphys.2022.1035538  

   Jadhav, Vidya V.; Han, Jian; Fasina, Yewande; Harrison, Scott H. (November 2022, Frontiers in Physiology)

   Monika Proszkowiec-Weglarz, Agricultural Research (Ed.)

   The chicken gastrointestinal tract has a diverse microbial community. There is increasing evidence for how this gut microbiome affects specific molecular pathways and the overall physiology, nervous system and behavior of the chicken host organism due to a growing number of studies investigating conditions such as host diet, antibiotics, probiotics, and germ-free and germ-reduced models. Systems-level investigations have revealed a network of microbiome-related interactions between the gut and state of health and behavior in chickens and other animals. While some microbial symbionts are crucial for maintaining stability and normal host physiology, there can also be dysbiosis, disruptions to nutrient flow, and other outcomes of dysregulation and disease. Likewise, alteration of the gut microbiome is found for chickens exhibiting differences in feather pecking (FP) behavior and this alteration is suspected to be responsible for behavioral change. In chickens and other organisms, serotonin is a chief neuromodulator that links gut microbes to the host brain as microbes modulate the serotonin secreted by the host’s own intestinal enterochromaffin cells which can stimulate the central nervous system via the vagus nerve. A substantial part of the serotonergic network is conserved across birds and mammals. Broader investigations of multiple species and subsequent cross-comparisons may help to explore general functionality of this ancient system and its increasingly apparent central role in the gut-brain axis of vertebrates. Dysfunctional behavioral phenotypes from the serotonergic system moreover occur in both birds and mammals with, for example, FP in chickens and depression in humans. Recent studies of the intestine as a major site of serotonin synthesis have been identifying routes by which gut microbial metabolites regulate the chicken serotonergic system. This review in particular highlights the influence of gut microbial metabolite short chain fatty acids (SCFAs) on the serotonergic system. The role of SCFAs in physiological and brain disorders may be considerable because of their ability to cross intestinal as well as the blood-brain barriers, leading to influences on the serotonergic system via binding to receptors and epigenetic modulations. Examinations of these mechanisms may translate into a more general understanding of serotonergic system development within chickens and other avians. 

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