Comprehensive assessment of functional effects of commonly used sweeteners on ex vivo human gut microbiome

The gut microbiome composition and function are associated with health and diseases. Sweeten-ers are widely used food additives, although many studies using animal models have linked sweetener consumption to gut microbial changes and health issues. Whether sweeteners directly change the human gut microbiome functionality remains largely unknown. In this study, we sys-tematically investigated the responses of five human gut microbiomes to 21 common sweeteners, using an approach combining high-throughput ex vivo microbiome culturing and metaproteomics to quantify functional changes in different taxa. Hierarchical clustering based on metaproteomic responses of individual microbiomes resulted in two clusters. The first cluster was composed of non-caloric artificial sweeteners (NAS) and two sugar alcohols with shorter carbon backbones (4-5 carbon atoms), and the second cluster was composed of sugar alcohols with longer carbon backbones. The metaproteomic functional responses of the second cluster were similar to the prebiotic fructooligosaccharides and kestose, indicating that these sugar alcohol-type sweeteners have potential prebiotic functions. This study provides a comprehensive evaluation of the direct effects of commonly used sweeteners on the functions of the human gut microbiome using a func-tional metaproteomics approach, improving our understanding of the roles of sweeteners on mi-crobiome-associated human health and disease issues.

Resilient T cell responses to B.1.1.529 (Omicron) SARS-CoV-2 variant

Emergence of the SARS-CoV-2 variant-of-concern (VOC) B.1.1.529 (Omicron) in late 2021 has raised alarm among scientific and health care communities due to a surprisingly large number of mutations in its spike protein. Public health surveillance indicates that the Omicron variant is significantly more contagious than the previously dominant VOC, B.1.617.2 (Delta). Several early reports demonstrated that Omicron exhibits a higher degree (~10-30-fold) of escape from antibody neutralization compared to earlier lineage variants. Therefore, it is critical to determine how well the second line of adaptive immunity, T cell memory, performs against Omicron in people following COVID-19 infection and/or vaccination. To that purpose, we analyzed a cohort (n=345 subjects) of two- or three- dose messenger RNA (mRNA) vaccine recipients and COVID-19 post infection subjects (including those receiving 2 doses of mRNA vaccine after infection), recruited to the CDC-sponsored AZ HEROES research study, alongside 32 pre-pandemic control samples. We report that T cell responses against Omicron spike peptides were largely preserved in all cohorts with established immune memory. IFN-gamma producing T cell responses remained equivalent to the response against the ancestral strain (WA1/2020), with some (<20%) loss in IL-2 single- or IL-2+IFN-gamma+ poly-functional responses. Three-dose vaccinated participants had similar responses to Omicron relative to convalescent or convalescent plus two-dose vaccinated groups and exhibited responses significantly higher than those receiving two mRNA vaccine doses. These results provide further evidence that a three-dose vaccine regimen benefits the induction of optimal functional T cell immune memory.

Longitudinal Chemical Gradients and the Functional Responses of Nutrients, Organic Matter, and Other Parameters to the Land Use Pattern and Monsoon Intensity

River water quality degradation is one of the hottest environmental issues worldwide. Therefore, monitoring water quality longitudinally and temporally is crucial for effective water management and contamination control. The main aim of this study was to assess the longitudinal variations in water quality in the mainstream of the Han River, Korea, from 2015 to 2019. The trophic state classification (TSC), microbial pollution indicator (MPI), and river pollution index (RPI) were calculated to characterize river water quality and revealed more serious pollution toward the downstream zone (Dz) due to agricultural and urban-dominated areas. The biodegradability index (BI) indicated that non-biodegradable organic pollutants are increasing in the water body from the urban and animal wastewater treatment plants. Nutrients, organic matter contents, total suspended solids, ionic factors, and algal chlorophyll were higher in the Dz than in any other zones and were markedly influenced by the summer monsoon. Empirical analysis showed that nutrients and organic matter had positive linear functional relations with agricultural and urban coverage and negative linear relations with forest coverage. The pollutant-transport function suggested that suspended solids act as TP and TN carriers. Regression analysis indicated that TP (R2 = 0.47) has more positive functional relations with algal growth than TN (R2 = 0.22). Our findings suggest that a combination of empirical models and pollution indices might be utilized to assess river water quality and that the resulting information could aid policymakers in managing the Han River.

Functional Responses of Phytoplankton Assemblages to Watershed Land Use and Environmental Gradients

Watershed land-use changes have been identified as major threats to lake fauna, subsequently affecting ecosystem functioning. In this study, the functional-based approach was used to examine the effects of land use and environmental changes on phytoplankton communities in four selected lakes in Northeast China. We also identified the sensitive functional traits as indicators of environmental stressors. The integration of RLQ analysis with the fourth-corner approach significantly identified five of 18 functional trait categories, including flagella, filamentous, unicellular, mixotrophic, and chlorophyll c, as potential indicators to changes in watershed land-use intensity and environmental gradients. Significant relationships between traits and land use and water quality highlighted the consequential indirect impact of extensive agricultural and urban development on phytoplankton via allochthonous nutrient inputs and various contaminants. In addition, the functional richness of phytoplankton assemblages generally increased along with surface area and forests, but decreased along with intensive agricultural and urban land use, implying that functional homogenization may cause a reduction in ecosystem productivity and reliability to land-use intensity. Given the superior performance of the functional-based approach, our findings also highlighted the importance of the application of both the biological traits and functional diversity index in monitoring programs for lake ecosystems.

rescomp: An R package for defining, simulating and visualizing ODE models of consumer-resource interactions

Mechanistic models of resource competition underpin numerous foundational concepts and theories in ecology, and continue to be employed widely to address diverse research questions. Nevertheless, current software tools present a comparatively steep barrier to entry. I introduce the R package rescomp to support the specification, simulation and visualisaton of a broad spectrum of consumer-resource interactions. rescomp is compatible with diverse model specifications, including an unlimited number of consumers and resources, different consumer functional responses (type I, II and III), different resource types (essential or substitutable) and supply dynamics (chemostats, logistic and/or pulsed), delayed consumer introductions, time dependent growth and consumption parameters, and instantaneous changes to consumer and/or resource densities. Several examples on implementing rescomp are provided. In addition, a wide variety of additional examples can be found in the package vignettes, including using rescomp to reproduce the results of several well known studies from the literature. rescomp provides users with an accessible tool to reproduce classic models in ecology, to specify models resembling a wide range of experimental designs, and to explore diverse novel model formulations.

Inferring Size-Based Functional Responses From the Physical Properties of the Medium

First derivations of the functional response were mechanistic, but subsequent uses of these functions tended to be phenomenological. Further understanding of the mechanisms underpinning predator-prey relationships might lead to novel insights into functional response in natural systems. Because recent consideration of the physical properties of the environment has improved our understanding of predator-prey interactions, we advocate the use of physics-based approaches for the derivation of the functional response from first principles. These physical factors affect the functional response by constraining the ability of both predators and prey to move according to their size. A physics-based derivation of the functional response should thus consider the movement of organisms in relation to their physical environment. One recent article presents a model along these criteria. As an initial validation of our claim, we use a slightly modified version of this model to derive the classical parameters of the functional response (i.e., attack rate and handling time) of aquatic organisms, as affected by body size, buoyancy, water density and viscosity. We compared the predictions to relevant data. Our model provided good fit for most parameters, but failed to predict handling time. Remarkably, this is the only parameter whose derivation did not rely on physical principles. Parameters in the model were not estimated from observational data. Hence, systematic discrepancies between predictions and real data point immediately to errors in the model. An added benefit to functional response derivation from physical principles is thus to provide easy ways to validate or falsify hypotheses about predator-prey relationships.

Endothelial Cells Promote Osteogenesis by Establishing a Functional and Metabolic Coupling With Human Mesenchymal Stem Cells

Bone formation involves a complex crosstalk between endothelial cells (EC) and osteodifferentiating stem cells. This functional interplay is greatly mediated by the paracrine and autocrine action of soluble factors released at the vasculature-bone interface. This study elucidates the molecular and functional responses triggered by this intimate interaction. In this study, we showed that human dermal microvascular endothelial cells (HMEC) induced the expression of pro-angiogenic factors in stem cells from human exfoliated deciduous teeth (SHED) and sustain their osteo-differentiation at the same time. In contrast, osteodifferentiating SHED increased EC recruitment and promoted the formation of complex vascular networks. Moreover, HMEC enhanced anaerobic glycolysis in proliferating SHED without compromising their ability to undergo the oxidative metabolic shift required for adequate osteo-differentiation. Taken together, these findings provide novel insights into the molecular mechanism underlying the synergistic cooperation between EC and stem cells during bone tissue renewal.

Hyperinflammatory environment drives dysfunctional myeloid cell effector response to bacterial challenge in COVID-19

COVID-19 displays diverse disease severities and symptoms including acute systemic inflammation and hypercytokinemia, with subsequent dysregulation of immune cells. Bacterial superinfections in COVID-19 can further complicate the disease course and are associated with increased mortality. However, there is limited understanding of how SARS-CoV-2 pathogenesis and hypercytokinemia impede the innate immune function against bacterial superinfections. We assessed the influence of COVID-19 plasma hypercytokinemia on the functional responses of myeloid immune cells upon bacterial challenges from acute-phase COVID-19 patients and their corresponding recovery (rec)-phase. We show that a severe hypercytokinemia status in COVID-19 patients correlates with the development of bacterial superinfections. Neutrophils and monocytes derived from COVID-19 patients in their acute-phase showed an impaired intracellular microbicidal capacity upon bacterial challenges. The impaired microbicidal capacity was reflected by abrogated MPO and reduced NETs production in neutrophils along with reduced ROS production in both neutrophils and monocytes. Moreover, we observed a distinct pattern of cell surface receptor expression on both neutrophils and monocytes, in line with suppressed autocrine and paracrine cytokine signaling. This phenotype was characterized by a high expression of CD66b, CXCR4 and low expression of CXCR1, CXCR2 and CD15 in neutrophils and low expression of HLA-DR, CD86 and high expression of CD163 and CD11b in monocytes. Furthermore, the impaired antibacterial effector function was mediated by synergistic effect of the cytokines TNF-α, IFN-γ and IL-4. COVID-19 patients receiving dexamethasone showed a significant reduction of overall inflammatory markers in the plasma as well as exhibited an enhanced immune response towards bacterial challenge ex vivo. Finally, broad anti-inflammatory treatment was associated with a reduction in CRP, IL-6 levels as well as length of ICU and hospital stay in critically ill COVID-19 patients. Our data provides insights into the transient functional dysregulation of myeloid immune cells against subsequent bacterial infections in COVID-19 patients and describe a beneficial role for the use of dexamethasone in these patients.