The first rudimentary evidence that the human body harbors a microbiota hinted at the complexity of host-associated microbial ecosystems. Now, almost 400 years later, a renaissance in the study of ...microbiota spatial organization, driven by coincident revolutions in imaging and sequencing technologies, is revealing functional relationships between biogeography and health, particularly in the vertebrate gut. In this Review, we present our current understanding of principles governing the localization of intestinal bacteria, and spatial relationships between bacteria and their hosts. We further discuss important emerging directions that will enable progressing from the inherently descriptive nature of localization and -omics technologies to provide functional, quantitative, and mechanistic insight into this complex ecosystem.
Tropini et al. review our understanding of the principles governing the localization of the gut microbiota, and spatial relationships between bacteria and their hosts. They also discuss emerging directions that will enable progressing from the descriptive nature of localization to providing functional, quantitative, and mechanistic insight into this complex ecosystem.
A correlate of protection (CoP) is urgently needed to expedite development of additional COVID-19 vaccines to meet unprecedented global demand. To assess whether antibody titers may reasonably ...predict efficacy and serve as the basis of a CoP, we evaluated the relationship between efficacy and in vitro neutralizing and binding antibodies of 7 vaccines for which sufficient data have been generated. Once calibrated to titers of human convalescent sera reported in each study, a robust correlation was seen between neutralizing titer and efficacy (ρ = 0.79) and binding antibody titer and efficacy (ρ = 0.93), despite geographically diverse study populations subject to different forces of infection and circulating variants, and use of different endpoints, assays, convalescent sera panels and manufacturing platforms. Together with evidence from natural history studies and animal models, these results support the use of post-immunization antibody titers as the basis for establishing a correlate of protection for COVID-19 vaccines.
Genomic technologies have significantly advanced our understanding of the composition and diversity of host-associated microbial populations. However, their spatial organization and functional ...interactions relative to the host have been more challenging to study. Here we present a pipeline for the assessment of intestinal microbiota localization within immunofluorescence images of fixed gut cross-sections that includes a flexible software package, BacSpace, for high-throughput quantification of microbial organization. Applying this pipeline to gnotobiotic and human microbiota-colonized mice, we demonstrate that elimination of microbiota-accessible carbohydrates (MACs) from the diet results in thinner mucus in the distal colon, increased proximity of microbes to the epithelium, and heightened expression of the inflammatory marker REG3β. Measurements of microbe-microbe proximity reveal that a MAC-deficient diet alters monophyletic spatial clustering. Furthermore, we quantify the invasion of Helicobacter pylori into the glands of the mouse stomach relative to host mitotic progenitor cells, illustrating the generalizability of this approach.
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•Single-cell imaging at tissue scales reveals spatial organization of gut microbiota•Absence of dietary fiber drives thinning of protective mucus layer•Microbe-microbe proximity measurement reveals monophyletic clustering is diet-dependent•BacSpace software enables large-scale quantitative image analysis
Earle et al. combine imaging methods with analysis software to enable high-resolution quantification of gut microbiota spatial organization in tissues. Their analysis reveals that elimination of microbiota-accessible carbohydrates from the diet results in thinner mucus, increased proximity of microbes to the epithelium, and heightened expression of inflammatory markers.
Background & Aims Diet has major effects on the intestinal microbiota, but the exact mechanisms that alter complex microbial communities have been difficult to elucidate. In addition to the direct ...influence that diet exerts on microbes, changes in microbiota composition and function can alter host functions such as gastrointestinal (GI) transit time, which in turn can further affect the microbiota. Methods We investigated the relationships among diet, GI motility, and the intestinal microbiota using mice that are germ-free (GF) or humanized (ex-GF mice colonized with human fecal microbiota). Results Analysis of gut motility revealed that humanized mice fed a standard polysaccharide-rich diet had faster GI transit and increased colonic contractility compared with GF mice. Humanized mice with faster transit due to administration of polyethylene glycol or a nonfermentable cellulose-based diet had similar changes in gut microbiota composition, indicating that diet can modify GI transit, which then affects the composition of the microbial community. However, altered transit in mice fed a diet of fermentable fructooligosaccharide indicates that diet can change gut microbial function, which can affect GI transit. Conclusions Based on studies in humanized mice, diet can affect GI transit through microbiota-dependent or microbiota-independent pathways, depending on the type of dietary change. The effect of the microbiota on transit largely depends on the amount and type (fermentable vs nonfermentable) of polysaccharides present in the diet. These results have implications for disorders that affect GI transit and gut microbial communities, including irritable bowel syndrome and inflammatory bowel disease.
The human intestine houses a dense microbial ecosystem in which the struggle for nutrients creates a continual and dynamic selective force. Host-produced mucus glycans provide a ubiquitous source of ...carbon and energy for microbial species. Not surprisingly, many gut resident bacteria have become highly adapted to efficiently consume numerous distinct structures present in host glycans. We propose that sophistication in mucus consumption is a trait most likely to be found in gut residents that have co-evolved with hosts, microbes that have adapted to the complexity associated with the host glycan landscape.
Abstract Maintaining wild animals in captivity has long been used for conservation and research. While often suggested that captivity causes chronic stress, impacts on the underlying stress ...physiology are poorly understood. We used wild-caught chukar (Alectoris chukar) as a model avian species to assess how the initial 10 days of captivity alters the corticosterone (CORT) secretory pathway. In the first few days of captivity, birds lost weight, had lower hematocrit and demonstrated changes in CORT concentrations. Both baseline and restraint-stress-induced CORT concentrations decreased by days 3–5 of captivity and remained significantly lower throughout the 10 days although stress-induced concentrations began to recover by day 9. To delineate potential mechanisms underlying these CORT changes, we evaluated alterations to the hypothalamic–pituitary–adrenal (HPA) axis. Although chukar appear to be resistant to arginine vasotocin’s (AVT) effects on CORT release, adrenocorticotropin hormone (ACTH) stimulated CORT release; however, ACTH stimulation did not differ during the 10 days of captivity. In contrast, negative feedback axis sensitivity, as determined by both dexamethasone suppression as well as endogenous negative feedback, decreased by day 5 but was regained by day 9. In addition, the combined stressors of capture and long distance transport eliminated the animals’ ability to mount an acute CORT response on the day following the move. Therefore, introduction into captivity appeared to shift the chukar into a temporary state of chronic stress that began to recover within 9 days. The duration of these alterations likely varies due to differences in capture techniques, transport distance, and species studied.
Genomic differences between gut-resident bacterial strains likely underlie significant interindividual variation in microbiome function. Traditional methods of determining community composition, such ...as 16S rRNA gene amplicon sequencing, fail to capture this functional diversity. Metagenomic approaches are a significant step forward in identifying strain-level sequence variants; however, given the current paucity of biochemical information, they too are limited to mainly low-resolution and incomplete functional predictions. Using genomic, biochemical, and molecular approaches, we identified differences in the fructan utilization profiles of two closely related
strains.
8736 (
) contains a fructan polysaccharide utilization locus (PUL) with a divergent
/
homolog gene pair that enables it to utilize inulin, differentiating this strain from other characterized
strains. Transfer of the distinct pair of
/
genes from
into the noninulin using type strain
resulted in inulin use by the recipient strain,
(
). The presence of the divergent
/
gene pair alone enabled the hybrid
(
) strain to outcompete the wild-type strain
in mice fed an inulin diet. Further, we discovered that the
/
homolog gene pair facilitated import of inulin into the periplasm without surface predigestion by an endo-acting enzyme, possibly due to the short average chain length of inulin compared to many other polysaccharides. Our data builds upon recent reports of dietary polysaccharide utilization mechanisms found in members of the
genus and demonstrates how the acquisition of two genes can alter the functionality and success of a strain within the gut.
Dietary polysaccharides play a dominant role in shaping the composition and functionality of our gut microbiota. Dietary interventions using these
icrobiota-
ccessible
arbohydrates (MACs) serve as a promising tool for manipulating the gut microbial community. However, our current gap in knowledge regarding microbial metabolic pathways that are involved in the degradation of these MACs has made the design of rational interventions difficult. The issue is further complicated by the diversity of pathways observed for the utilization of similar MACs, even in closely related microbial strains. Our current work focuses on divergent fructan utilization pathways in two closely related
strains and provides an integrated approach to characterize the molecular basis for strain-level functional differences.
ABSTRACT Genomic differences between gut-resident bacterial strains likely underlie significant interindividual variation in microbiome function. Traditional methods of determining community ...composition, such as 16S rRNA gene amplicon sequencing, fail to capture this functional diversity. Metagenomic approaches are a significant step forward in identifying strain-level sequence variants; however, given the current paucity of biochemical information, they too are limited to mainly low-resolution and incomplete functional predictions. Using genomic, biochemical, and molecular approaches, we identified differences in the fructan utilization profiles of two closely related Bacteroides thetaiotaomicron strains. B. thetaiotaomicron 8736 (Bt-8736) contains a fructan polysaccharide utilization locus (PUL) with a divergent susC/susD homolog gene pair that enables it to utilize inulin, differentiating this strain from other characterized Bt strains. Transfer of the distinct pair of susC/susD genes from Bt-8736 into the noninulin using type strain B. thetaiotaomicron VPI-5482 resulted in inulin use by the recipient strain, Bt(8736-2). The presence of the divergent susC/susD gene pair alone enabled the hybrid Bt(8736-2) strain to outcompete the wild-type strain in vivo in mice fed an inulin diet. Further, we discovered that the susC/susD homolog gene pair facilitated import of inulin into the periplasm without surface predigestion by an endo-acting enzyme, possibly due to the short average chain length of inulin compared to many other polysaccharides. Our data builds upon recent reports of dietary polysaccharide utilization mechanisms found in members of the Bacteroides genus and demonstrates how the acquisition of two genes can alter the functionality and success of a strain within the gut. IMPORTANCE Dietary polysaccharides play a dominant role in shaping the composition and functionality of our gut microbiota. Dietary interventions using these microbiota-accessible carbohydrates (MACs) serve as a promising tool for manipulating the gut microbial community. However, our current gap in knowledge regarding microbial metabolic pathways that are involved in the degradation of these MACs has made the design of rational interventions difficult. The issue is further complicated by the diversity of pathways observed for the utilization of similar MACs, even in closely related microbial strains. Our current work focuses on divergent fructan utilization pathways in two closely related B. thetaiotaomicron strains and provides an integrated approach to characterize the molecular basis for strain-level functional differences.
Preparing nursing students for diverse populations Kirby, Kristen F.; Earle, Melinda; Calahan, Charles A. ...
Nurse education in practice,
August 2021, 2021-08-00, 20210801, Letnik:
55
Journal Article
Recenzirano
To improve undergraduate nursing students and educator intercultural knowledge and competencies by implementing an academic systems change.
Many organizations have diversity and inclusion guidelines ...and initiatives for healthcare providers to consider in determining culturally competent care, which has a direct impact on the care given, received, and overall outcomes.
1. Assess student’s mindset at the beginning and the end of an undergraduate nursing course. 2. Ensure diversity and inclusion content was provided to faculty through a continuing education program. 3. Review all undergraduate courses for diversity and inclusion content.
The Intercultural Development Inventory®, a 50-item cross-cultural, theory-based assessment tool was used in a pre- and post-test design (n = 61 intervention; n = 56 control) to determine undergraduate nursing student’s mindset and assists the student’s in developing a personalized Intercultural Development Plan. The effectiveness of faculty diversity and inclusion education was evaluated using a post program evaluation. Curricular blueprinting of all undergraduate nursing courses for diversity and inclusion content was completed.
The results demonstrated a statistically significant difference in the post-test between the intervention and control groups.
While evidence is lacking in specificity of how to best implement diversity and inclusion content in curriculum, these results provided some excellent baseline data that can be tracked while continued changes occur.
•Literature distinguishes the importance of cultural competence, diversity, and inclusion work among professionals.•There is minimal literature specific to nursing which describes how to change or implement the topic in a school of nursing.•The results demonstrate a statistically significant difference in the post-test between the intervention and control group.•The results provide some excellent baseline data while continual changes, assessment, and evaluation occur.
Erratic blood glucose levels can be a cause and consequence of delayed gastric emptying in patients with diabetes. It is unknown if better glycemic control increases risks of hypoglycemia or improves ...hemoglobin A1c levels and gastrointestinal symptoms in diabetic gastroparesis. This study investigated the safety and potential efficacy of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in poorly controlled diabetes with gastroparesis. Forty-five type 1 or 2 patients with diabetes and gastroparesis and hemoglobin A1c >8% from the NIDDK Gastroparesis Consortium enrolled in a 24 week open-label pilot prospective study of CSII plus CGM. The primary safety outcome was combined numbers of mild, moderate, and severe hypoglycemic events at screening and 24 weeks treatment. Secondary outcomes included glycemic excursions on CGM, hemoglobin A1c, gastroparesis symptoms, quality-of-life, and liquid meal tolerance. Combined mild, moderate, and severe hypoglycemic events occurred similarly during the screening/run-in (1.9/week) versus treatment (2.2/week) phases with a relative risk of 1.18 (95% CI 0.85-1.64, P = 0.33). CGM time in hypoglycemia (<70 mg/dL) decreased from 3.9% to 1.8% (P<0.0001), time in euglycemia (70-180 mg/dL) increased from 44.0% to 52.0% (P = 0.02), time in severe hyperglycemia (>300 mg/dL) decreased from 14.2% to 7.0% (P = 0.005), and hemoglobin A1c decreased from 9.4±1.4% to 8.3±1.3% (P = 0.001) on CSII plus CGM. Symptom scores decreased from 29.3±7.1 to 21.9±10.2 with lower nausea/vomiting, fullness/early satiety, and bloating/distention scores (P≤0.001). Quality-of-life scores improved from 2.4±1.1 to 3.1±1.1 (P<0.0001) and volumes of liquid nutrient meals tolerated increased from 420±258 to 487±312 mL (P = 0.05) at 24 weeks. In conclusion, CSII plus CGM appeared to be safe with minimal risks of hypoglycemic events and associated improvements in glycemic control, gastroparesis symptoms, quality-of-life, and meal tolerance in patients with poorly controlled diabetes and gastroparesis. This study supports the safety, feasibility, and potential benefits of improving glycemic control in diabetic gastroparesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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