An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint.

At the species level, immunity depends on the selection and transmission of protective components of the immune system. A microbe-induced population of RORγ-expressing regulatory T cells (Tregs) is essential in controlling gut inflammation. We uncovered a non-genetic, non-epigenetic, non-microbial mode of transmission of their homeostatic setpoint. RORγ+ Treg proportions varied between inbred mouse strains, a trait transmitted by the mother during a tight age window after birth but stable for life, resistant to many microbial or cellular perturbations, then further transferred by females for multiple generations. RORγ+ Treg proportions negatively correlated with IgA production and coating of gut commensals, traits also subject to maternal transmission, in an immunoglobulin- and RORγ+ Treg-dependent manner. We propose a model based on a double-negative feedback loop, vertically transmitted via the entero-mammary axis. This immunologic mode of multi-generational transmission may provide adaptability and modulate the genetic tuning of gut immune responses and inflammatory disease susceptibility.

Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans.

According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli, which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education.

Reconstruction of ancient microbial genomes from the human gut.

Loss of gut microbial diversity1-6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000-2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.

Systematically assessing microbiome-disease associations identifies drivers of inconsistency in metagenomic research.

Evaluating the relationship between the human gut microbiome and disease requires computing reliable statistical associations. Here, using millions of different association modeling strategies, we evaluated the consistency-or robustness-of microbiome-based disease indicators for 6 prevalent and well-studied phenotypes (across 15 public cohorts and 2,343 individuals). We were able to discriminate between analytically robust versus nonrobust results. In many cases, different models yielded contradictory associations for the same taxon-disease pairing, some showing positive correlations and others negative. When querying a subset of 581 microbe-disease associations that have been previously reported in the literature, 1 out of 3 taxa demonstrated substantial inconsistency in association sign. Notably, >90% of published findings for type 1 diabetes (T1D) and type 2 diabetes (T2D) were particularly nonrobust in this regard. We additionally quantified how potential confounders-sequencing depth, glucose levels, cholesterol, and body mass index, for example-influenced associations, analyzing how these variables affect the ostensible correlation between Faecalibacterium prausnitzii abundance and a healthy gut. Overall, we propose our approach as a method to maximize confidence when prioritizing findings that emerge from microbiome association studies.

Leveraging vibration of effects analysis for robust discovery in observational biomedical data science.

Hypothesis generation in observational, biomedical data science often starts with computing an association or identifying the statistical relationship between a dependent and an independent variable. However, the outcome of this process depends fundamentally on modeling strategy, with differing strategies generating what can be called "vibration of effects" (VoE). VoE is defined by variation in associations that often lead to contradictory results. Here, we present a computational tool capable of modeling VoE in biomedical data by fitting millions of different models and comparing their output. We execute a VoE analysis on a series of widely reported associations (e.g., carrot intake associated with eyesight) with an extended additional focus on lifestyle exposures (e.g., physical activity) and components of the Framingham Risk Score for cardiovascular health (e.g., blood pressure). We leveraged our tool for potential confounder identification, investigating what adjusting variables are responsible for conflicting models. We propose modeling VoE as a critical step in navigating discovery in observational data, discerning robust associations, and cataloging adjusting variables that impact model output.

Exploring the Botanical Origins of Bee-Collected Pollen: A Comprehensive Historical and Contemporary Analysis.

Bee-collected pollen is one of the most important bee products. In order to predict its chemical composition and nutritional value botanical origin of pollen plays a crucial role. This review intended to collect all available data published about botanical origin of pollen collected all around the world. Due to enourmous amount of data and variables nonlinear principal component analysis (NLPCA), by applying Categorical Principal Component Analysis (CATPCA), was conducted in order to try to determine any specifity and/or differences among samples. Also, importance of some plant families/genera/species for bees was monitored. Based on CATPCA results families can serve in order to distinct samples from North/South America. Also, some samples from Europe (Turkey and Serbia) were characterized with presence of some specific families. Genera were excellent tool to distinguish samples from different parts of Brazil as well as Australia, Asia and Africa. Due to high and specific biodiversity pollen samples obtained from Sonoran desert (USA) completely were separated during analysis. This review presents the first attempt to summarize and classify a large number of data about botanical sources of bee-collected pollen.

Unlocking Quercetin's Neuroprotective Potential: A Focus on Bee-Collected Pollen.

In the quest to evade side effects associated with synthetic drugs, mankind is continually exploring natural sources. In recent decades, neurodegenerative disorders (NDDs) have surged dramatically compared to other human diseases. Flavonoids, naturally occurring compounds, have emerged as potential preventers of NDD development. Notably, quercetin and its derivatives demonstrated excellent antioxidant properties in the fight against NDDs. Recognizing bee-collected pollen (BP) as a well-established excellent source of quercetin and its derivatives, this review seeks to consolidate available data on the prevalence of this flavonoid in BP, contingent upon its botanical and geographical origins. It aims to advocate for BP as a superb natural source of "drugs" that could serve as preventative measures against NDDs. Examination of numerous published articles, detailing the phenolic profile of BP, suggests that it can be a great source of quercetin, with an average range of up to 1000 mg/kg. In addition to quercetin, 24 derivatives (with rutin being the most predominant) have been identified. Theoretical calculations, based on the recommended dietary intake for quercetin, indicate that BP can fulfil from 0.1 to over 100 % of the requirement, depending on BP's origin and bioaccessibility/bioavailability during digestion.

Inflammatory bowel disease as a model for translating the microbiome.

The inflammatory bowel diseases (IBDs) are among the most closely studied chronic inflammatory disorders that involve environmental, host genetic, and commensal microbial factors. This combination of features has made IBD both an appropriate and a high-priority platform for translatable research in host-microbiome interactions. Decades of epidemiology have identified environmental risk factors, although most mechanisms of action remain unexplained. The genetic architecture of IBD has been carefully dissected in multiple large populations, identifying several responsible host epithelial and immune pathways but without yet a complete systems-level explanation. Most recently, the commensal gut microbiota have been found to be both ecologically and functionally perturbed during the disease, but with as-yet-unexplained heterogeneity among IBD subtypes and individual patients. IBD thus represents perhaps the most comprehensive current model for understanding the human microbiome's role in complex inflammatory disease. Here, we review the influences of the microbiota on IBD and its potential for translational medicine.

Food nanoemulsions: how simulated gastrointestinal digestion models, nanoemulsion, and food matrix properties affect bioaccessibility of encapsulated bioactive compounds.

Food nanoemulsions are known as very effective and excellent carriers for both lipophilic and hydrophilic bioactive compounds (BCs) and have been successfully used for controlled delivery and protection of BCs during gastrointestinal digestion (GID). However, due to sensitive and fragile morphology, BCs-loaded nanoemulsions have different digestion pathways depending on their properties, food matrix properties, and applied models for testing their digestibility and BCs bioaccessibility. Thus, this review gives a critical review of the behavior of encapsulated BCs into food nanoemulsions during each phase of GID in different static and dynamic in vitro digestion models, as well as of the influence of nanoemulsion and food matrix properties on BCs bioaccessibility. In the last section, the toxicity and safety of BCs-loaded nanoemulsions evaluated on in vitro and in vivo GID models have also been discussed. Better knowledge of food nanoemulsions' behavior in different models of simulated GI conditions and within different nanoemulsion and food matrix types can help to standardize the protocol for their testing aiming for researchers to compare results and design BCs-loaded nanoemulsions with better performance and higher targeted BCs bioaccessibility.

Food nanoemulsions are effective and excellent carriers for bioactive compounds (BCs).Nanoemulsions are often subject to morphological and structural changes during digestion.BC-s loaded nanoemulsions have different digestion pathways in different digestion models.BC-s have different bioaccessibility in different nanoemulsion models.Food matrix can affect the bioaccessibility of BCs entrapped in nanoemulsions.

Okara-Enriched Gluten-Free Bread: Nutritional, Antioxidant and Sensory Properties.

The aim of this study was to produce an eco-innovative gluten-free bread with a pleasant taste and a unique formulation that includes the highest quality grains and pseudocereals (buckwheat; rice; and millet); and okara; a by-product of soy milk production. The mixture of pseudocereal and cereal flour contained buckwheat flour 45%, rice flour 33%, and millet flour 22%. Three gluten-free breads; each containing different contents of gluten-free flour (90%, 80%, and 70%, respectively); okara (10%, 20%, and 30%, respectively); and a control sample (without okara); were prepared and subjected to sensory evaluation. The okara-enriched gluten-free bread with the highest sensory score was selected for further analysis of physico-chemical (total proteins; total carbohydrates; insoluble fiber; soluble fiber; sugars; total lipids; saturated fatty acids; and salt) and functional properties (total phenolic content and antioxidant properties). The highest sensory scores were obtained for 30% okara-enriched gluten-free bread including taste; shape; odor; chewiness; and cross-section properties; classifying this bread in the category of very good quality and excellent quality (mean score 4.30 by trained evaluators and 4.59 by consumers). This bread was characterized by a high content of dietary fiber (14%), the absence of sugar; low content of saturated fatty acids (0.8%), rich source of proteins (8.8%) and certain minerals (e.g.,; iron; zinc); and low energy value (136.37 kcal/100g DW). Total phenolic content was 133.75 mgGAE/100g FW; whereas ferric reducing power; ABTS radical cation; and DPPH radical scavenging activity were 119.25 mgAA/100g FW; 86.80 mgTrolox/100g FW; and 49.92 mgTrolox/100g FW; respectively. Okara addition in gluten-free bread production enables the formulation of high-nutritive; good antioxidative; low-energy bread; and better soy milk waste management.

Composition of proteins in fresh whey as waste in tofu processing.

Tofu whey is a pale-yellowish liquid with specific aroma/taste which remains as the byproduct/waste after tofu squeezing and represents an environmental problem for direct disposal. Understanding the fresh tofu whey protein composition and the activity of bioactive peptides could be useful for the application of tofu whey as a functional food additive. Tofu whey was obtained during the tofu production from six soybean genotypes by hydrothermal processing in combination with chymosin-pepsin rennet. Basic 7S globulin (14.28-19.13%), γ-conglycinin (7.73-9.31%) and ß-conglycinin (10.59-12.90%) were registered of the total extracted proteins. Glycinin was present with a dominant share of acidic (24.64-27.55%) versus basic polypeptides (12.18-14.61%) in the total extracted proteins. High content of total protein (22.67-28.00%), balanced content (9.76-13.33% of the total extracted proteins) and residual activity (1.95-3.76%) of trypsin inhibitors and low lectins content (5.04-5.48% of the total extracted proteins) indicate good nutritional value of the tofu whey samples. Tofu whey can be potentially useful for application as a cheap, nutritional and functional food additive and can enable sustainable production through the recycling of waste.

Spatial distribution of major and trace elements in artificial lakes in Serbia: health risk indices and suitability of water for drinking and irrigation purposes.

Lakes and reservoirs are the main water resources for household, irrigation, and industrial use. Hence, it is necessary to control water pollution and have reliable information on water quality, which refers to its suitability for a particular purpose. The main objective of this study was to evaluate the suitability of water for drinking and irrigation purposes from ten artificial lakes on the territory of the Republic of Serbia. The physicochemical parameters were determined using standard analytical methods, whereas the optical emission spectrometry with inductively coupled plasma, ICP-OES, was used to determine the concentrations of 23 macro-, micro-, and trace elements in water. Health risk indices of drinking water and its suitability for irrigation purposes were evaluated. The results of physicochemical parameters, except for total organic matter, indicated that most samples were within the recommended values. Among analyzed elements, the concentration of Mg was elevated in the water of the lakes Srebrno and Prvonek. The results of health risk assessment clearly showed that there was no acute health risk (HQA < 1), whereas long-term risk (HQL) in the studied lakes was observed with respect to As (lakes Grliste and Srebrno), Mn (lakes Srebrno and Prvonek), Ni (Lake Vrutci), and Sr (Lake Grliste). The irrigation criteria indicated that the water from the examined lakes had satisfactory quality for this purpose, except for residual sodium carbonates (RSC). This criterion indicated low quality or unsuitability of the water in 7 lakes. The main outcomes provided valuable information on the suitability of water from the artificial lakes for intended uses.

Hieracium waldsteinii (Asteraceae) and Onosma stellulata (Boraginaceae) as a Source of Antioxidant and Antimicrobial Agents.

The current study aimed to phytochemically characterize (including a detailed phenolic profile) two endemic Balkan's species (Hieracium waldsteinii and Onosma stellulata) and determine their possible application as a source of natural antioxidant and antimicrobial agents. The main phenolic compound in both species (in all examined parts) was chlorogenic acid. Eriodictyol, genistein and naringenin were quantified only in H. waldsteinii while isorhamnetin-3-O-rutinoside and sinapic acid were characteristic for O. stellulata. The highest antioxidant activity (98 mg AAE/g dry weight for TAC assay) was ascribed to the flower extract of H. waldsteinii while the lowest results (∼4.3 mg AAE/g dry weight for FRP assay) were exhibited by the extracts obtained from the plant's stem. Antimicrobial assays showed moderate antibacterial, i. e., moderate/strong activity against several tested fungi (in particular Trichoderma viride). Correlation analysis revealed strong positive connection between phenolic compounds and reducing power of extracts as well as between total phenolic and flavonoid content and the obtained minimal inhibitory concentration recorded in antibacterial assays.

Micro/trace/toxic elements and insecticide residues level in monofloral bee-collected sunflower pollen- health risk assessment.

The aim of the current research was to determine the content of (potentially) toxic elements and insecticide residues in monofloral sunflower bee-collected pollen. For micro- and trace elements determination Inductively Coupled Plasma Optical Emission (ICP-OES) analytical method was used while insecticide residue content was monitored by applying Liquid Chromatography-Mass Spectrometry (LC-MS/MS) technique. In total, seventeen micro/trace elements were quantified. None of the twenty four examined insecticides were detected above the limit of detection (LOD) which makes studied sunflower bee-collected pollen eco-friendly both to bees and humans. Based on presence of several toxic as well as potentially toxic elements calculations for estimated weekly intakes (EWI), and oral intakes (OI) were made and used for health risk assessment based on the computation of two different health risk quotients (HQ)- acute (HQA) and long-term (HQL). The obtained results proved that all HQ values for adults were negligible or low except in case of HQL value for arsenic (0.32) which can be characterized as medium. However, in case of children much more precaution is needed due to significant HQL risk for arsenic (1.511). The attained data can help to make additional linkage between bee-collected pollen as food ingredients and potential benefits/risks for human health.

A systematic machine learning and data type comparison yields metagenomic predictors of infant age, sex, breastfeeding, antibiotic usage, country of origin, and delivery type.

The microbiome is a new frontier for building predictors of human phenotypes. However, machine learning in the microbiome is fraught with issues of reproducibility, driven in large part by the wide range of analytic models and metagenomic data types available. We aimed to build robust metagenomic predictors of host phenotype by comparing prediction performances and biological interpretation across 8 machine learning methods and 4 different types of metagenomic data. Using 1,570 samples from 300 infants, we fit 7,865 models for 6 host phenotypes. We demonstrate the dependence of accuracy on algorithm choice and feature definition in microbiome data and propose a framework for building microbiome-derived indicators of host phenotype. We additionally identify biological features predictive of age, sex, breastfeeding status, historical antibiotic usage, country of origin, and delivery type. Our complete results can be viewed at http://apps.chiragjpgroup.org/ubiome_predictions/.

Exploring host-microbiota interactions in animal models and humans.

The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host-microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host-microbiota interactions and explore recent human microbiome studies.

Trypsin inhibitor content and activity of soaking water whey as waste in soy milk processing.

Soybean soaking water whey (SWW) is obtained as the waste of soy milk production and mostly represents an environmental problem. The aim of this study was to assess the content of proteins and content and activity of trypsin inhibitors of fresh SWW, obtained during soy milk production. Two zones of Bowman-Birk trypsin inhibitors (BBI) were detected. One was identified as a monomeric form of BBI (0.61-2.93%) and the other one was identified as a polymeric form of BBI (0.45-3.33%). The degree of BBI extraction (1.88-5.49%) was influenced by the soybean genotype and the grain size, i.e. it increased with increasing grain size. Kunitz trypsin inhibitor was not detected. Total proteins were found in traces in SWW (0.03-0.06%). Low residual trypsin inhibitor activity (0.32-0.55%) suggested that SWW can potentially be applied for preparing food or feed. In that case it will not be waste but a cheap functional supplement with BBI as a biologically active component.

Correlation between multiple cerebral aneurysms and a rare type of segmental duplication of the middle cerebral artery.

BACKGROUND: Connection between the duplication of the middle cerebral artery (DMCA) and the presence of multiple aneurysms has been described in a small number of cases. CASE PRESENTATION: The presence of a rare type of DMCA associated with cerebral aneurysms was diagnosed in 56 year old woman after a rupture of an aneurysm on the dorsal segment of the DMCA. .. The presence of equal diameters of branches of the DMCA and anterior cerebral artery (ACA) could be recorded as trifurcation of the carotid internal artery (ICA). However, due to the anastomosis of the DMCA branches in the area of the M2 segment, the recorded anatomical change represented a segmental duplication of MCA. Three aneurysms that were directly related to the segmental DMCA were diagnosed. CONCLUSIONS: Anatomical variation by type of segmental DMCA is a rare subtype of DMCA. The presence of multiple aneurysms associated with this type of anatomical variation in MCA indicates their high hemodynamic instability.

Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children.

Viruses have long been considered potential triggers of autoimmune diseases. Here we defined the intestinal virome from birth to the development of autoimmunity in children at risk for type 1 diabetes (T1D). A total of 220 virus-enriched preparations from serially collected fecal samples from 11 children (cases) who developed serum autoantibodies associated with T1D (of whom five developed clinical T1D) were compared with samples from controls. Intestinal viromes of case subjects were less diverse than those of controls. Among eukaryotic viruses, we identified significant enrichment of Circoviridae-related sequences in samples from controls in comparison with cases. Enterovirus, kobuvirus, parechovirus, parvovirus, and rotavirus sequences were frequently detected but were not associated with autoimmunity. For bacteriophages, we found higher Shannon diversity and richness in controls compared with cases and observed that changes in the intestinal virome over time differed between cases and controls. Using Random Forests analysis, we identified disease-associated viral bacteriophage contigs after subtraction of age-associated contigs. These disease-associated contigs were statistically linked to specific components of the bacterial microbiome. Thus, changes in the intestinal virome preceded autoimmunity in this cohort. Specific components of the virome were both directly and inversely associated with the development of human autoimmune disease.