Luminal Environment Research Articles

Post Occupancy Evaluation of the Luminous Environment in Algerian University Classrooms

The luminous environment is one of the most important physical parameters in a teaching space (classroom) due to its impact on the intellectual performance of students, their health and their behavior. The aim of this study is to evaluate the luminous environment in university classrooms located in Constantine, the main university hub of the East of Algeria. A Post Occupancy Evaluation (POE) based on the objective and subjective assessment was carried out at the Department of Psychology of Constantine 2 University in North and West facing classrooms. This study was conducted during the three periods: winter, spring and summer, under clear sky and overcast sky conditions. The objective variables measured by a luxmeter during each course session are: indoor illuminance levels (Ei) on work plan, vertical illuminance levels on boards (Ev), uniformity index (Uo) and outdoor illuminance levels (Ex). At the same time, students perception and satisfaction were reported by a longitudinal questionnaire (N=1221) using subjective scales. The objective assessment shows that the mean interior illuminance is dependent of the sky-type, and it varies with outdoor illuminance. We notice that illuminance levels in north classroom are below the recommended value especially under overcast sky. The illuminance levels in west facing classroom are excessive during the afternoon under clear sunny sky. However, students show a remarkable degree of adaptation to different light levels. They use controls to modify the light level at their work plans.

Natural light optimization in an existing primary school: human centred design and daylight retrofitting solutions for students wellbeing

How the human centred design solutions will implement the benefit of daylighting in an existing primary school? This paper shows research experiences on students visual comfort inside the school building Don Milani, in Prato (Italy). The layout of training spaces, distribution and functional organization is also re-designed as flexible/resilient space/place, with a focus on the control of natural light effects for the luminous environment quality, vision and perception, but also an energy consumption reduction. The project is based on a human centred design approach, fostering the integration between sustainable lighting, human perception and biological clock (i.e. circadian rhythm) connected to the Sun daily path. Results showed the importance of natural light optimization to assure different children activities and behaviour, reorganization of the indoor environment and work/observation stations, combining the light colour variability of different materials. Findings highlighted that natural light quality assessment is fundamental to achieve not only a good lighting quality and energy consumption reduction, but also high level of visual comfort in learning spaces, implementing both the students wellbeing and their proactive behaviour, as it should be in a sustainable school building.

Theoretical and experimental analysis of the passengers reading comfort to luminous environment in Chinese high-speed trains

Theoretical and experimental analysis of the passengers reading comfort to luminous environment in Chinese high-speed trains

Fibrinogen-Related Protein, Fgl2, of Hamster Cauda Epididymal Fluid: Enzymatic Characterization, and Identification of Fgl2-Binding Proteins and Ligand of Defective Hamster Sperm Organelles.

The luminal environment of the mammalian epididymidis performs a dual function; sperm maturation and maintaining sperm viability. We previously identified a secretory protein (260/280KDa oligomers) of hamster cauda epididymal principal cells that binds to nonviable sperm. The 260/280KDa oligomers are composed of 64kDa FGL2 (fibrinogen-like protein-2) and 33kDa FGL1) (fibrinogen-like protein-1). The potential mechanism by which FGL2 binds to degenerative sperm is not clearly demonstrated. In this study, we report the downstream sequence of prothrombinase activity of FGL2, the identification of organelles, and characterize candidate proteins that bind FGL2. The following reaction sequence confirms that FGL2 is a phospholipid-activated serine protease; the conversion of prothrombin to thrombin by FGL2, followed by the conversion of soluble fibrinogen to insoluble fibrin polymers by thrombin. FGL2 binds intensely to tails than heads of de-membranated sperm. A spectrum of polypeptides of cauda sperm tails binds to FGL2. Proteomic analyses of 65KDa, 16kDa, and 13kDa polypeptides of tails correspond to a-Kinase anchor protein 4, glutathione peroxidase 4, and cytochrome c oxidase subunit 4, respectively. Annexin V, a calcium-dependent phosphatidylserine-binding protein localized to the flagellum and co-precipitated with FGL2. We have demonstrated a novel protective mechanism for recognizing and eliminating defective spermatozoa from viable sperm population.

Canna starch improves immune functions and the intestinal environment in mice.

The present study was conducted to elucidate the dietary effects of canna starch on the immune functions and intestinal luminal environment in mice. The amylose and resistant starch characteristics were determined for six types of starch, including edible canna. Canna starch was found to be higher in amylose and resistant starch compared with the other starches. BALB/c mice were fed 3.16% (low-canna group) and 6.32% (high-canna group) canna starch for 2 weeks, and then intestinal parameters were measured. Fecal IgA and mucin levels were markedly elevated by canna starch intake. IgA levels in serum and spleen lymphocytes were elevated by canna starch intake in the high-canna group, but not in the low-canna group. When the mice were fed canna starch, the cecum weight increased, and the pH in the cecum decreased. The high-canna group had significantly increased levels of Clostridium subcluster XIVa lactic acid, acetic acid, and n-butyric acid in the cecum compared with the control group. These results suggested that canna starch supplementation changed the intestinal microbiota and enhanced the intestinal immune and barrier functions and cecal organic acids in mice.

Immunolocalisation of aquaporins 3, 7, 9 and 10 in the epididymis of three wild ruminant species (Iberian ibex, mouflon and chamois) and sperm cryoresistance.

In the epididymis, epithelial cells manage changes in the luminal environment for proper sperm maturation. Moreover, aquaglyceroporins, a subgroup of aquaporins (AQP), modulate the transport of water, glycerol and other small molecules in epithelial cells. We aim to characterise the lining epithelium, quantify its cell composition and immunolocalise the aquaglyceroporins AQP3, AQP7, AQP9 and AQP10 alongside the epididymal ductus of three wild ruminant species, and to determine if species-specific differences could be associated with cauda sperm cryoresistance variations. Epididymides from Iberian ibex (n =5), mouflon (n =5) and chamois (n =6) were obtained. Cauda spermatozoa were collected and sperm parameters were analysed before and after freezing. Histology and immunohistochemistry of AQP3, 7, 9, 10 and T-CD3 were performed in the caput, corpus and cauda epididymal regions. This work first describes the lining epithelium in Iberian ibex, mouflon and chamois epididymis along the three anatomical regions, consisting of principal, basal, apical, clear and halo cells. However, the percentage of each cell type differed in ibex compared to mouflon and chamois. The positive T-CD3 immunolabeling of all the halo cells confirmed their T-lymphocyte nature. Aquaglyceroporin expression patterns were similar among species, except for differences in AQP7 and AQP10 immunolocalisation in ibex. Species-specific differences in epididymal sperm cryoresistance were confirmed. The epididymal epithelium of the three wild ruminants differ in their relative number of cell types and AQP immunolocalisation, which ultimately appears to affect cauda epidydimal spermatozoa cryoresistance. Our study provides information on the relevance of the quantitative composition and AQP pattern expression in epididymal lining epithelium on sperm cryoresistance.

Capturing Luminous Flux Entering Human Eyes with a Camera, Part 1: Fundamentals

ABSTRACT A space occupant’s real-time exposure to light reaching his/her eyes has been a concern in lighting research and design practice. This study assumed a schematic eye to estimate the luminous flux received by the entrance pupil from the visible luminous environment. As the first part of this study, this paper focused on the fundamentals of luminous flux calculation that considers real-time human eye reactions. The research work includes: (a) developing a dynamic binocular/monocular visual field model that takes the eye movement into account, based on a conventional visual field model in orthomode, (b) retrieving the apparent area of the entrance pupil of the schematic eye, and (c) quantifying the light passing through the entrance pupil from the luminous environment fallen in the binocular/monocular visual field. The fundamental theory was tested in a theoretical uniform lighting scene to calculate the luminous flux emitted from the human visual field along multiple gaze directions at different light levels. A foundation was thus laid to estimate the real-time luminous flux passing through the entrance pupil with the aid of the camera as disclosed in Part 2 of the present study.

High-fat diet promotes the effect of fructo-oligosaccharides on the colonic luminal environment, including alkaline phosphatase activity in rats

We recently reported that fermentable nondigestible carbohydrates such as oligosaccharides, commonly increase colonic alkaline phosphatase (ALP) activity and the gene expression of Alpi-1, coding for rat intestinal alkaline phosphatase-I isozyme in rats and that the effect of oligosaccharides on colonic ALP activity is affected by the quality of dietary fats. We hypothesized that the amount of dietary fat would modulate the effect of oligosaccharides on colonic ALP and luminal environment in rats. In experiment 1, male Sprague-Dawley rats were fed a low-fat (LF, 5% lard) or high-fat (HF, 30% lard) diet with or without 4% fructo-oligosaccharides (FOS). In experiment 2, they were fed a 2.5%, 7%, 20%, or 40% fat (lard) diet with 4% FOS for 2 weeks. Dietary FOS in the HF diet (HF-FOS) significantly increased ALP activity in the colon and cecal digesta and colonic expression of Alpi-1, but not in the LF diet with FOS groups (LF-FOS). In comparison to the LF-FOS group, the increases in fecal mucins, Lactobacillus ratio, as well as cecal n-butyrate, and the decrease in fecal Clostridium coccoides, were more pronounced in the HF-FOS group. Compared with the 2.5% or 7% fat + FOS diet, the 20% fat + FOS diet significantly increased colonic ALP activity, Alpi-1 expression, and fecal mucins. These factors did not differ significantly between 20% and 40% fat + FOS diets. To exert the maximum effect of FOS on the colonic luminal environment, including ALP activity in rats, significantly more fat may be required than that contained present a LF diet.

The enteric nervous system.

Of all the organ systems in the body, the gastrointestinal tract is the most complicated in terms of the numbers of structures involved, each with different functions, and the numbers and types of signaling molecules utilized. The digestion of food and absorption of nutrients, electrolytes, and water occurs in a hostile luminal environment that contains a large and diverse microbiota. At the core of regulatory control of the digestive and defensive functions of the gastrointestinal tract is the enteric nervous system (ENS), a complex system of neurons and glia in the gut wall. In this review, we discuss 1) the intrinsic neural control of gut functions involved in digestion and 2) how the ENS interacts with the immune system, gut microbiota, and epithelium to maintain mucosal defense and barrier function. We highlight developments that have revolutionized our understanding of the physiology and pathophysiology of enteric neural control. These include a new understanding of the molecular architecture of the ENS, the organization and function of enteric motor circuits, and the roles of enteric glia. We explore the transduction of luminal stimuli by enteroendocrine cells, the regulation of intestinal barrier function by enteric neurons and glia, local immune control by the ENS, and the role of the gut microbiota in regulating the structure and function of the ENS. Multifunctional enteric neurons work together with enteric glial cells, macrophages, interstitial cells, and enteroendocrine cells integrating an array of signals to initiate outputs that are precisely regulated in space and time to control digestion and intestinal homeostasis.

Preliminary investigation on the human response to patterned chromatic glazing

Daylighting has been associated with improved mood, enhanced morale, increased visual comfort and reduced fatigue. Glazing with varying transmittance, colour or configuration may have significant effects on the quality and quantity of daylight within a building, thus good glazing design has posed significant challenges for building designers. Coloured glazing is broadly applied in modern offices worldwide and many studies have explored the effect of this glazing on human performance. Commonly studied are chromatic glazing typologies which offer a unidirectional shift in the colour of light to either bronze or blue. This alters the spectral ability of the glazing and thus changes the indoor luminous environment. It is reported that although occupants prefer warm light, people perform better under cool light condition. This project aims to implement patterns in chromatic glazing to introduce a two-directional colour distortion to alter the colorimetric characteristics of the glazing, heavily affecting the user's perception and performance in the luminous environment. More specifically, seven different indoor luminous conditions were created using various patterned chromatic glazing (100% CAR Blue, 70% CAR Blue, 30% CAR Blue, neutral clear glazing, 30% CAR Bronze, 70% CAR Bronze, and 100% CAR Bronze) to investigate their effect on human perception using a scaled test room (1:3 scaling) to simulate office working conditions. Both subjective (questionnaire on pleasantness, comfort, alertness) and objective (an achromatic Landolt ring test and a chromatic Landolt ring test) evaluations were carried out for the proposed window conditions. The results suggest that the patterned chromatic glazing conditions create a more desirable luminous indoor environment, as well as a more efficient working environment. The 30% blue and 70% blue glazing improved feelings of visual comfort compared to the 100% blue, whilst retaining the efficiency of task completion. Meanwhile the 30% bronze glazing increased the efficiency of task completion compared to the 100% bronze, whilst retaining the ratings for comfort and pleasantness. This implies that the design of patterned chromatic glazing which introduces the combination of two chromatic glazing may be a feasible solution to improve the indoor luminous environment.

Abstract IA008: Modeling immune-epithelial interactions in health and disease using human intestinal enteroid co-cultures

Abstract Human intestinal enteroids derived from Lgr5+ actively dividing adult stem cells offer a relevant ex vivo system to study biological processes of the human small intestine and colon. While these primary cultures recreate cellular and functional features of the intestinal epithelium of the small intestine (enteroids) or colon (colonoids), they are limited by the lack of associated cell types, including immunological cells, nerves, stromal cells that help maintain tissue homeostasis and respond to external challenges. In the gut, innate immune cells interact with the epithelium by conducting lumial surveillance, support barrier function, and deploy effector functions in response to injury/damage. We have established a co-culture system of enteroid/colonoid monolayers and underlying macrophages and polymorphonuclear neutrophils to recapitulate the cellular framework of the human intestinal epithelial niche. Human intestinal enteroids can generated from biopsies or resected tissue from any segment of the human intestine/colon and maintained in long-term cultures in a basement membrane-rich matrix supplemented with growth factor-conditioned media necessary to maintain intestinal stem cell homeostasis. Immune cells are isolated from fresh human whole blood or frozen peripheral blood mononuclear cells (PBMC) and co-cultured with human intestinal enteroids/colonoids grown as confluent monolayers on permeable supports (e.g., Transwells). This configuration allows for controlled access to the apical side of the epithelium to mimic the gut luminal environment as well as the basolateral side occupied by immune cells to mimic the mucosal environment. Enteroid-immune co-cultures enable multiple outcome measures, including transepithelial resistance, production of cytokines/chemokines, phenotypic analysis of immune cells, tissue immunofluorescence imaging, protein or mRNA expression, antigen or microbe uptake, and other cellular functions. Citation Format: Nicholas C. Zachos. Modeling immune-epithelial interactions in health and disease using human intestinal enteroid co-cultures [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr IA008.

실내 루버형 집광채광 시스템의 조명 디밍 제어시스템에 따른 실내 조도 분포 분석

Lighting dimming systems are used for energy reduction and user convenience in various buildings. However, after installing the dimming system, it is difficult to satisfy the required illuminance of the indoor workplane due to the adjustment of the shading device, the inflow of surrounding lighting system, and daylight. Therefore, this study identified the variations of workplane illuminances by installing and monitoring photosensors in various locations to provide an appropriate luminous environment to users. This study analyzed the energy savings of lighting dimming control systems with the indoor reflective louver system and found that the average energy savings was 29.77%, when the sky condition was partly cloudy. Linear regression analysis was performed using an order least square to determine the relationship with the average illuminance of the working surface of each photosensor. As a result, it was confirmed that the R-squared value for indoor reflective louver system was 0.939 for lighting fixture photosensors, 0.908 for three way photosensors, 0.908 for two way photosensors and 0.779 for wall photosensors.

Research on an environmental adaptive feature extraction algorithm

The visual simultaneous localization and mapping (SLAM) system is prone to tracking failure in complex and variable environments and lighting change environments. Therefore, an adaptive S-piecewise from an accelerated segment test (FAST) and boosted efficient binary local image descriptor or BEBLID (ASFB) feature extraction algorithm is proposed to obtain better matching results and more accurate poses. The algorithm designs a segment function adaptive thresholding FAST feature extraction algorithm based on the sigmoid function trajectory. It also calculates different thresholds for each pixel point in the image to complete the feature extraction, which adaptively calculates the threshold value for different luminance environments, to improve the quality of feature points, and uses BEBLID instead of binary robust independent elementary feature (BRIEF) to complete the description of feature points, which improves the accuracy of description information. The experiment selects KITTI and Euroc datasets, and the results show that the ASFB feature extraction algorithm performs better than the oriented FAST and rotated BRIEF algorithm in both the illumination changing environment and the normal environment. In addition, the bit pose accuracy is also improved. Moreover, it can meet the operational efficiency requirements of the SLAM algorithm.

Efficient and simple genetic engineering of enteroids using mouse isolated crypts for investigating intestinal functions

Intestinal epithelial cells separate subepithelial tissues from luminal environment formed with food, incoming pathogens, and resident intestinal microbiota, etc., and elicit various intestinal function. Enteroid, a three-dimensional culture system of small intestinal epithelial cells, has been widely used for analyzing the intestinal function, further a transgenic enteroid was developed to investigate the molecular mechanisms. However, conventional transgenic enteroid production method, which transfer gene into single stem cells, has limitations including low efficiency and time-consuming. Here we show that by gene transfer into small intestinal isolated crypts maintaining stem cell niche, a transgenic enteroid was obtained quickly and efficiently. Isolated crypts were transfected by lentiviral vector without separating into single cells, and transgenic enteroid composed of all lineages of intestinal epithelial cells was generated at day 7 with yield of 56%, maintaining the intestinal function in drug transport and innate immunity. Our efficient and simple transgenic enteroid generation method enables high-throughput investigation of intestinal epithelial cells and contributes to understanding intestinal function.

Designing Natural Atmosphere in Office Environment Through Daylight Responsive Dynamic Lighting

Often the criteria for designing office lighting is to increase efficiency through a bright and evenly distributed lighting. Yet, research has found that this static lighting leads to an unstimulating, boring, and dull luminous environment that supports neither task focus, nor a pleasant atmosphere. The goal of this paper is to create a closer connection to a natural light environment by designing an office lighting that inspired by light as natural phenomenon creates a lively and more nature-based atmosphere. We developed a lighting design with focus on analysing the perceived atmosphere as a metric for a dynamic lighting design for a meeting room of a real estate company in Denmark. Through a mixed method approach, we explore the design factors that determine the desired natural atmosphere. Our design aims at enhancing the function of the meeting room as a formal space where negotiations are held by 1) presenting the identity of the company to the business partners; and 2) supporting employees’ sense of belonging to the company culture. As a result, our lighting design creates a lighting hierarchy in line with the architectural elements of the space, complementing daylight through electric lighting in a dynamic way, accounting for both sky-type and daylight inflow.

Porosomes in uterine epithelial cells: Ultrastructural identification and characterization during early pregnancy.

Porosomes are plasma membrane structures in secretory cells that allow transient docking and/or partial fusion of vesicles during which they release their content then disengage. This is referred to as "kiss and run" exocytosis. During early pregnancy, at the time of receptivity, there is a high level of vesicle activity in uterine epithelial cells (UECs). One of the secretory pathways for these vesicles could be via porosomes, which have yet to be identified in UECs. This study identified porosomes in the apical plasma membrane of UECs for the first time. These structures were present on days 1, 5.5, and 6 of early pregnancy, where they likely facilitate partial secretion via "kiss and run" exocytosis. The porosomes were measured and quantified on days 1, 5.5, and 6, which showed there are significantly more porosomes on day 5.5 (receptive) compared to day 1 (nonreceptive) of pregnancy. This increase in porosome numbers may reflect major morphological and molecular changes in the apical plasma membrane at this time such as increased cholesterol and soluble NSF attachment proteinreceptorproteins, as these are structural and functional components of the porosome complex assembly. Porosomes were observed in both resting (inactive) and dilated (active) states on days 1, 5.5, and 6 of early pregnancy. Porosomes on day 5.5 are significantly more active than on day 1 as demonstrated by the dilation of their base diameter. Further two-way ANOVA analysis of base diameter in resting and dilated states found a significant increase in porosome activity in day 5.5 compared to day 1. This study therefore indicates an increase in the number and activity of porosomes at the time of uterine receptivity in the rat, revealing a mechanism by which the UECs modify the uterine luminal environment at this time.

Chlorogenic Acid and Quercetin in a Diet with Fermentable Fiber Influence Multiple Processes Involved in DSS-Induced Ulcerative Colitis but Do Not Reduce Injury.

Ulcerative colitis (UC) patients often avoid foods containing fermentable fibers as some can promote symptoms during active disease. Pectin has been identified as a more protective fermentable fiber, but little has been done to determine the interaction between pectin and bioactive compounds present in foods containing that fiber type. Quercetin and chlorogenic acid, two bioactives in stone fruits, may have anti-cancer, anti-oxidant, and anti-inflammatory properties. We hypothesized that quercetin and chlorogenic acid, in the presence of the fermentable fiber pectin, may suppress the expression of pro-inflammatory molecules, alter the luminal environment, and alter colonocyte proliferation, thereby protecting against recurring bouts of UC. Rats (n = 63) received one of three purified diets (control, 0.45% quercetin, 0.05% chlorogenic acid) containing 6% pectin for 3 weeks before exposure to dextran sodium sulfate (DSS, 3% for 48 h, 3x, 2 wk separation, n = 11/diet) in drinking water to initiate UC, or control (no DSS, n = 10/diet) treatments prior to termination at 9 weeks. DSS increased the fecal moisture content (p < 0.05) and SCFA concentrations (acetate, p < 0.05; butyrate, p < 0.05). Quercetin and chlorogenic acid diets maintained SLC5A8 (SCFA transporter) mRNA levels in DSS-treated rats at levels similar to those not exposed to DSS. DSS increased injury (p < 0.0001) and inflammation (p < 0.01) scores, with no differences noted due to diet. Compared to the control diet, chlorogenic acid decreased NF-κB activity in DSS-treated rats (p < 0.05). Quercetin and chlorogenic acid may contribute to the healthy regulation of NF-κB activation (via mRNA expression of IκΒα, Tollip, and IL-1). Quercetin enhanced injury-repair molecule FGF-2 expression (p < 0.01), but neither diet nor DSS treatment altered proliferation. Although quercetin and chlorogenic acid did not protect against overt indicators of injury and inflammation, or fecal SCFA concentrations, compared to the control diet, their influence on the expression of injury repair molecules, pro-inflammatory cytokines, SCFA transport proteins, and NF-κB inhibitory molecules suggests beneficial influences on major pathways involved in DSS-induced UC. Therefore, in healthy individuals or during periods of remission, quercetin and chlorogenic acid may promote a healthier colon, and may suppress some of the signaling involved in inflammation promotion during active disease.

Lighting Quality Self-assessment in Italian Home Offices

The spread of information technology and the improvement of telecommunicating systems have changed the way to conceive work. People performing typical office activities provided with a laptop and an internet connection can work in whatever place: a coffee house, a waiting room of a train station, an airport, or their own home. The habit to work at home has amazingly spread due to the Covid-19 pandemic, arising crucial questions. Are home work-stations comfortable enough to work? Are lighting conditions of residential spaces proper to perform typical office activities? This paper presents a survey investigating the typical characteristics of the luminous environment in home working spaces (considering both daylight and electric light) and people’s average awareness about light and lighting-connected themes. The research has been carried out through an online questionnaire addressed to home workers and students forced to stay home because of the Covid-19 spread. The results demonstrated that many interviewees have difficulties in managing light and are not completely aware of the right actions to take to improve lighting quality of home workplaces. Moreover, a complete lack of knowledge about electric light has emerged. So, popularizing more knowledge about light and lighting-connected themes is prominent. Indeed, now and even more in the future, people will work in places other than the traditional workplaces, for which standards regulating lighting characteristics do not exist. In this context, the definition of ad hoc guidelines and the spread of best practices should be a crucial goal for researchers and experts in lighting.

The phenotype of the gut region is more stably retained than developmental stage in piglet intestinal organoids.

Intestinal organoids are innovative in vitro tools to study the digestive epithelium. The objective of this study was to generate jejunum and colon organoids from suckling and weaned piglets in order to determine the extent to which organoids retain a location-specific and a developmental stage-specific phenotype. Organoids were studied at three time points by gene expression profiling for comparison with the transcriptomic patterns observed in crypts in vivo. In addition, the gut microbiota and the metabolome were analyzed to characterize the luminal environment of epithelial cells at the origin of organoids. The location-specific expression of 60 genes differentially expressed between jejunum and colon crypts from suckling piglets was partially retained (48%) in the derived organoids at all time point. The regional expression of these genes was independent of luminal signals since the major differences in microbiota and metabolome observed in vivo between the jejunum and the colon were not reproduced in vitro. In contrast, the regional expression of other genes was erased in organoids. Moreover, the developmental stage-specific expression of 30 genes differentially expressed between the jejunum crypts of suckling and weaned piglets was not stably retained in the derived organoids. Differentiation of organoids was necessary to observe the regional expression of certain genes while it was not sufficient to reproduce developmental stage-specific expression patterns. In conclusion, piglet intestinal organoids retained a location-specific phenotype while the characteristics of developmental stage were erased in vitro. Reproducing more closely the luminal environment might help to increase the physiological relevance of intestinal organoids.

Intestinal transgene delivery with native E. coli chassis allows persistent physiological changes

SUMMARYLive bacterial therapeutics (LBTs) could reverse diseases by engrafting in the gut and providing persistent beneficial functions in the host. However, attempts to functionally manipulate the gut microbiome of conventionally raised (CR) hosts have been unsuccessful because engineered microbial organisms (i.e., chassis) have difficulty in colonizing the hostile luminal environment. In this proof-of-concept study, we use native bacteria as chassis for transgene delivery to impact CR host physiology. Native Escherichia coli bacteria isolated from the stool cultures of CR mice were modified to express functional genes. The reintroduction of these strains induces perpetual engraftment in the intestine. In addition, engineered native E. coli can induce functional changes that affect physiology of and reverse pathology in CR hosts months after administration. Thus, using native bacteria as chassis to “knock in” specific functions allows mechanistic studies of specific microbial activities in the microbiome of CR hosts and enables LBT with curative intent.