Differential Modulation of Mouse Intestinal Organoids with Fecal Luminal Factors from Obese, Allergic, Asthmatic Children.

Asthma is a multifactorial condition that can be associated with obesity. The phenotypes of asthma in lean and obese patients are different, with proinflammatory signatures being further elevated in the latter. Both obesity and asthma are associated with alterations in intestinal barrier function and immunity, and with the composition of the intestinal microbiota and food consumption. In this study, we aimed to establish an organoid model to test the hypothesis that the intestinal content of lean and obese, allergic, asthmatic children differentially regulates epithelial intestinal gene expression. A model of mouse jejunum intestinal organoids was used. A group of healthy, normal-weight children was used as a control. The intestinal content of asthmatic obese children differentially induced the expression of inflammatory and mitochondrial response genes (Tnf-tumor necrosis factor, Cd14, Muc13-mucin 13, Tff2-Trefoil factor 2 and Tff3, Cldn1-claudin 1 and 5, Reg3g-regenerating family member 3 gamma, mt-Nd1-NADH dehydrogenase 1 and 6, and mt-Cyb-mitochondrial cytochrome b) via the RAGE-advanced glycosylation end product-specific receptor, NF-κB-nuclear factor kappa b and AKT kinase signal transduction pathways. Fecal homogenates from asthmatic normal-weight and obese children induce a differential phenotype in intestinal organoids, in which the presence of obesity plays a major role.

Evaluating SWAG and Its Validity When Compared to 3D Imagery of Secondarily Grafted Cleft Sites.

OBJECTIVE: To test validity of 2D Standardized Way to Assess Grafts (SWAG) ratings to assess 3D outcomes of bone grafting (ABG). PATIENTS: 43 patients (34 UCLP, 9 BCLP) with non-syndromic complete clefts, bone-grafted at mean age 9yrs/3mos, with available post-graft occlusal radiographs and cone beam computed tomography (CBCT) (taken mean 4yrs/9mos post-ABG). MAIN OUTCOME MEASURES: 2D occlusal radiographs rated twice using SWAG by 6 calibrated raters. 12 scores were averaged and converted to a percentage reflecting bone-fill. Weighted Kappas were assessed for SWAG reliability. 3D cleft-site bone volume was calculated by 1 rater using ITK-SNAP. 13 cleft sites were re-measured by the 'one rater' for 3D reliability using Intraclass Correlation Coefficient (ICC). 2D versus 3D ratings were compared using paired t-test, independent samples t-test, Bland-Altman and Linear Regression. Significance level was P = .5. RESULTS: 2D reliability was 0.724 (intra-rater) and 0.546 (inter-rater). 3D reliability was 0.986. Bland-Altman plot comparing 2D vs 3D showed for 45 of 47 graft-sites were within 2 SD's. Mean % bone-fill was 64.11% with 2D and 69.06% with 3D (mean difference = 4.95%) that was a non-significant difference in both t-tests. Regression showed a statistically significant relation between the two methods (r2 = 0.46; P = .0001). CONCLUSION: 2D SWAG systematically and non-significantly underestimated bone-fill. There was a significant correlation between 2D/3D methods. Bland-Altman analysis illustrated the similarity of the two methods. For comparisons of group (cleft treatment Centers') bone grafting outcomes, the 2D method may suffice as a proxy for the 3D method. However, with individual variation up to 40% in 2D estimates of actual 3D volume, 2D SWAG method cannot be used in place of 3D images.

From Non-Alcoholic Fatty Liver Disease to Liver Cancer: Microbiota and Inflammation as Key Players.

It is estimated that 25% of the world's population has non-alcoholic fatty liver disease. This disease can advance to a more severe form, non-alcoholic steatohepatitis (NASH), a disease with a greater probability of progression to cirrhosis and hepatocellular carcinoma (HCC). NASH could be characterized as a necro-inflammatory complication of chronic hepatic steatosis. The combination of factors that lead to NASH and its progression to HCC in the setting of inflammation is not clearly understood. The portal vein is the main route of communication between the intestine and the liver. This allows the transfer of products derived from the intestine to the liver and the hepatic response pathway of bile and antibody secretion to the intestine. The intestinal microbiota performs a fundamental role in the regulation of immune function, but it can undergo changes that alter its functionality. These changes can also contribute to cancer by disrupting the immune system and causing chronic inflammation and immune dysfunction, both of which are implicated in cancer development. In this article, we address the link between inflammation, microbiota and HCC. We also review the different in vitro models, as well as recent clinical trials addressing liver cancer and microbiota.

The Interplay between Microbiota and Chemotherapy-Derived Metabolites in Breast Cancer.

The most common cancer in women is breast cancer, which is also the second leading cause of death in this group. It is, however, important to note that some women will develop or will not develop breast cancer regardless of whether certain known risk factors are present. On the other hand, certain compounds are produced by bacteria in the gut, such as short-chain fatty acids, secondary bile acids, and other metabolites that may be linked to breast cancer development and mediate the chemotherapy response. Modeling the microbiota through dietary intervention and identifying metabolites directly associated with breast cancer and its complications may be useful to identify actionable targets and improve the effect of antiangiogenic therapies. Metabolomics is therefore a complementary approach to metagenomics for this purpose. As a result of the combination of both techniques, a better understanding of molecular biology and oncogenesis can be obtained. This article reviews recent literature about the influence of bacterial metabolites and chemotherapy metabolites in breast cancer patients, as well as the influence of diet.

Resistance of Argopecten purpuratus scallop larvae to vibriosis is associated with the front-loading of immune genes and enhanced antimicrobial response.

Mass mortality events caused by vibriosis have emerged in hatchery-reared scallop larvae from Chile, threatening scallop aquaculture. In an attempt to mitigate this emerging infectious disease and provide candidates for marker-assisted selective breeding, we tested here the existence of a genetic component of Argopecten purpuratus scallop resistance to the pathogen Vibrio bivalvicida. Through a dual RNA-seq approach we analyzed the basal transcriptome and the transcriptional response to infection in two resistant and two susceptible families as well as the pathogen transcriptomic response to host colonization. The results highlighted a genetic basis in the resistance of scallop larvae to the pathogen. The Vibrio response was characterized by a general metabolic adaptation to the host environment, along with several predicted virulence factors overexpressed in infected scallop larvae with no difference between resistant and susceptible host phenotypes. On the host side, several biological processes were enriched in uninfected resistant larvae. Within these enriched categories, immune-related processes were overexpressed, while morphogenesis, biomineral tissue development, and angiogenesis were under expressed. Particularly, genes involved in immune recognition and antimicrobial response, such as lipopolysaccharide-binding proteins (LBPs), lysozyme, and bactericidal permeability-increasing protein (BPI) were overexpressed in uninfected resistant larvae. As expected, immune-related biological processes were enriched in Vibrio-infected larvae, but they were more numerous in resistant larvae. Overexpressed immune genes in response to infection included several Toll-like receptors, TNF and NF-κB immune signaling genes, and the antimicrobial peptide Big defensin ApBD1. Results strongly suggest that both a front-loading of immune genes and an enhanced antimicrobial response to infection contribute to the resistance, while pathogen infective strategy does not discriminate between host phenotypes. Overall, early expression of host immune genes appears as a strong determinant of the disease outcome that could be used in marker-assisted selective breeding.

The Allergenic Activity of Blo t 2, a Blomia tropicalis IgE-Binding Molecule.

Only few allergens derived from house dust mite (HDM) species have been evaluated in terms of their potential to induce allergic inflammation. In this study, we aimed to evaluate different aspects of the allergenicity and allergenic activity of Blo t 2, a Blomia tropicalis allergen. Blo t 2 was produced as a recombinant protein in Escherichia coli. Its allergenic activity was tested in humans by skin prick test and basophil activation assays, and in mice, by passive cutaneous anaphylaxis and a model of allergic airway inflammation. Sensitization rate to Blo t 2 (54.3%) was similar to that found to Blo t 21 (57.2%) and higher than to Der p 2 (37.5%). Most Blo t 2-sensitized patients showed a low intensity response (99.5%). Blo t 2 elicited CD203c upregulation and allergen induced skin inflammation. Additionally, immunized animals produced anti-Blo t 2 IgE antibodies and passive transfer of their serum to non-immunized animals induced skin inflammation after allergen exposure. Immunized animals developed bronchial hyperreactivity and a strong inflammatory lung reaction (eosinophils and neutrophils). These results confirm the allergenic activity of Blo t 2 and supports its clinical relevance.

Gut Microbiota and Breast Cancer: The Dual Role of Microbes.

Breast cancer is the most frequently diagnosed cancer and also one of the leading causes of mortality among women. The genetic and environmental factors known to date do not fully explain the risk of developing this disease. In recent years, numerous studies have highlighted the dual role of the gut microbiota in the preservation of host health and in the development of different pathologies, cancer among them. Our gut microbiota is capable of producing metabolites that protect host homeostasis but can also produce molecules with deleterious effects, which, in turn, may trigger inflammation and carcinogenesis, and even affect immunotherapy. The purpose of this review is to describe the mechanisms by which the gut microbiota may cause cancer in general, and breast cancer in particular, and to compile clinical trials that address alterations or changes in the microbiota of women with breast cancer.

Early Secondary Alveolar Bone Grafting and Facial Growth of Patients with Complete Unilateral Cleft Lip and Palate.

OBJECTIVE: To investigate the craniofacial growth outcomes of early secondary alveolar bone grafting(ABG) around 6 years of age. DESIGN: Retrospective cohort study. SETTING: 1 North-American and 5 Northern-European cleft centers. SUBJECTS: 33 subjects with CUCLP consecutively treated with secondary ABG around 6 years of age were compared to 105 subjects from 4 centers treated with late secondary ABG and 19 subjects from 1 center with primary ABG. METHODS: Preorthodontic standardized lateral cephalometric radiographs taken after 12 years of age were traced and analyzed according to the Eurocleft Study protocol. Fourteen angular and two proportional measurements were performed. Measurement means from the Study Center(SC) were compared to 5 Northern-European centers using analysis of variance and Welch's modified t-tests, and P < .05 was considered statistically significant. RESULTS: For the SC, the mean age ± SD at the time of bone graft was 5.85 ± 0.71 years and the mean age at the time of the lateral cephalogram was 13.4 ± 1.8 years. The sagittal maxillary prominence of the SC was favorably comparable to the 5 Northern-European centers. The mean SNA (78.1 ± 4.3) for the SC was significantly higher compared to 4 of the 5 Northern-European centers(all P < .05), and the mean ANB angle was comparable to 4 of the 5 centers. Similarly, the mean soft tissue ANB angle was not significantly different to the 5 centers. The soft tissue vertical proportions compared favorably to all 5 Northern-European centers(all P < .01). CONCLUSIONS: Craniofacial growth outcomes of early secondary ABG around 6 years compare favorably to the outcomes of late secondary ABG.

[Circulación de Leishmania infantum y Trypanosoma cruzi en perros domésticos de áreas urbanas de Sincelejo, región Caribe de Colombia].

Introducción. La enfermedad de Chagas y la leishmaniasis tradicionalmente se han considerado zoonosis endémicas de áreas rurales del país. Sin embargo, la aparición de casos de estas enfermedades en áreas urbanas sugiere nuevos ciclos de circulación de estos parásitos. Por esta razón, se ha propuesto a los perros como centinelas de estos agentes zoonóticos, dado su rol como huéspedes accidentales o reservorios. Objetivo. Evaluar la circulación silenciosa de Leishmania spp. y Trypanosoma cruzi en perros de zonas urbanas de la ciudad de Sincelejo, Sucre. Materiales y métodos. Se analizaron 100 muestras de sangre de perros para amplificar la región ITS1 de Leishmania spp. Las muestras positivas se utilizaron para amplificar la región conservada del minicírculo del ADN del cinetoplasto de Leishmania infantum y para el análisis de polimorfismos de longitud de fragmentos de restricción con la endonucleasa HaeIII. Por otra parte, se amplificó un fragmento del ADN satelital de T. cruzi. Además, se evaluó la presencia de infecciones por Ehrlichia canis y Anaplasma platys, como potencialmente modificadoras de las manifestaciones clínicas. Resultados. De los 100 perros estudiados, se detectó: Leishmania spp. en 32, T. cruzi en 12, ambos parásitos en 7 y L. infantum en 18. Se encontraron infecciones por anaplasmatáceos en 18, y coinfecciones por bacterias y parásitos en 8 de los perros. En general, 47 de los animales estaban infectados por, al menos, un agente etiológico. Conclusión. Se demuestra la circulación de L. infantum y T. cruzi en zonas urbanas de Sincelejo, así como coinfecciones de estos parásitos junto con parásitos de la familia Anaplasmataceae. El presente estudio demuestra la conveniencia del uso de perros en la vigilancia epidemiológica de estos agentes zoonóticos.

Circulación de Leishmania infantum y Trypanosoma cruzi en perros domésticos de áreas urbanas de Sincelejo, región Caribe de Colombia / Silent circulation of Leishmania infantum and Trypanosoma cruzi among urban dogs from Sincelejo city, Caribbean region of Colombia

Introducción. La enfermedad de Chagas y la leishmaniasis tradicionalmente se han considerado zoonosis endémicas de áreas rurales del país. Sin embargo, la aparición de casos de estas enfermedades en áreas urbanas sugiere nuevos ciclos de circulación de estos parásitos. Por esta razón, se ha propuesto a los perros como centinelas de estos agentes zoonóticos, dado su rol como huéspedes accidentales o reservorios. Objetivo. Evaluar la circulación silenciosa de Leishmania spp. y Trypanosoma cruzi en perros de zonas urbanas de la ciudad de Sincelejo, Sucre. Materiales y métodos. Se analizaron 100 muestras de sangre de perros para amplificar la región ITS1 de Leishmania spp. Las muestras positivas se utilizaron para amplificar la región conservada del minicírculo del ADN del cinetoplasto de Leishmania infantum y para el análisis de polimorfismos de longitud de fragmentos de restricción con la endonucleasa HaelII. Por otra parte, se amplificó un fragmento del ADN satelital de T. cruzi. Además, se evaluó la presencia de infecciones por Ehrlichia canis y Anaplasma platys, como potencialmente modificadoras de las manifestaciones clínicas. Resultados. De los 100 perros estudiados, se detectó: Leishmania spp. en 32, T. cruzi en 12, ambos parásitos en 7 y L. infantum en 18. Se encontraron infecciones por anaplasmatáceos en 18, y coinfecciones por bacterias y parásitos en 8 de los perros. En general, 47 de los animales estaban infectados por, al menos, un agente etiológico. Conclusión. Se demuestra la circulación de L. infantum y T. cruzi en zonas urbanas de Sincelejo, así como coinfecciones de estos parásitos junto con parásitos de la familia Anaplasmataceae. El presente estudio demuestra la conveniencia del uso de perros en la vigilancia epidemiológica de estos agentes zoonóticos.

Introduction: Leishmania infantum and Trypanosoma cruzi are considered endemic zoonotic agents in rural areas of the country; however, there is a high risk of urbanization due to anthropogenic processes. For this reason, dogs have been proposed as sentinels of these zoonoses given their role as patients, hosts and/or reservoirs. Objective: To assess the silent circulation of Leishmania spp. and T. cruzi parasites in canines from urban areas of Sincelejo, Sucre. Materials and methods: One hundred canine blood samples were used to amplify the ITS1 region of Leishmania spp. Positive samples were used to amplify the conserved region of the kinetoplast DNA minicircle of L. infantum and for restriction fragment length polymorphism analysis with HaelII endonuclease. In addition, a satellite DNA of T. cruzi was amplified. Also, the presence of Ehrlichia canis and Anaplasma platys was evaluated as infections that can influence clinical symptoms and health of animals. Results: Leishmania spp. was detected in 32% (32/100) and T. cruzi in 12% (12/100) of the animals, and 7% (7/100) of the samples were positive for both parasites. Also, L. infantum and infections with Anaplasmataceae family parasites were both detected in 18 % (18/100) of the samples. In the same way, co-infections with bacteria and parasites were found in 8 % (8/100) of the animals. Overall, 47 % (47/100) of the animals were infected with at least one agent. Conclusion: The circulation of L. infantum and T. cruzi, as well as co-infections of pathogens of the Anaplasmataceae family, is demonstrated in urban areas of Sincelejo. The present study demonstrates the convenience of canines as epidemiological surveillance sentinels of these zoonotic agents.

Paradoxical Radiosensitizing Effect of Carnosic Acid on B16F10 Metastatic Melanoma Cells: A New Treatment Strategy.

Carnosic acid (CA) is a phenolic diterpene characterized by its high antioxidant activity; it is used in industrial, cosmetic, and nutritional applications. We evaluated the radioprotective capacity of CA on cells directly exposed to X-rays and non-irradiated cells that received signals from X-ray treated cells (radiation induced bystander effect, RIBE). The genoprotective capacity was studied by in vivo and in vitro micronucleus assays. Radioprotective capacity was evaluated by clonogenic cell survival, MTT, apoptosis and intracellular glutathione assays comparing radiosensitive cells (human prostate epithelium, PNT2) with radioresistant cells (murine metastatic melanoma, B16F10). CA was found to exhibit a genoprotective capacity in cells exposed to radiation (p < 0.001) and in RIBE (p < 0.01). In PNT2 cells, considered as normal cells in our study, CA achieved 97% cell survival after exposure to 20 Gy of X-rays, eliminating 67% of radiation-induced cell death (p < 0.001), decreasing apoptosis (p < 0.001), and increasing the GSH/GSSH ratio (p < 0.01). However, the administration of CA to B16F10 cells decreased cell survival by 32%, increased cell death by 200% (p < 0.001) compared to irradiated cells, and increased cell death by 100% (p < 0.001) in RIBE bystander cells (p < 0.01). Furthermore, it increased apoptosis (p < 0.001) and decreased the GSH/GSSG ratio (p < 0.01), expressing a paradoxical radiosensitizing effect in these cells. Knowing the potential mechanisms of action of substances such as CA could help to create new applications that would protect healthy cells and exclusively damage neoplastic cells, thus presenting a new desirable strategy for cancer patients in need of radiotherapy.

Dietary Polysaccharides as Modulators of the Gut Microbiota Ecosystem: An Update on Their Impact on Health.

A polysaccharide is a macromolecule composed of more than ten monosaccharides with a wide distribution and high structural diversity and complexity in nature. Certain polysaccharides are immunomodulators and play key roles in the regulation of immune responses during the progression of some diseases. In addition to stimulating the growth of certain intestinal bacteria, polysaccharides may also promote health benefits by modulating the gut microbiota. In the last years, studies about the triad gut microbiota-polysaccharides-health have increased exponentially. In consequence, in the present review, we aim to summarize recent knowledge about the function of dietary polysaccharides on gut microbiota composition and how these effects affect host health.

Dietary Polysaccharides and Gut Microbiota Ecosystem.

The intestinal microbiota is a community of microorganisms that subsists within the gastrointestinal ecosystem [...].

Bifidobacterium longum subsp. infantis CECT 7210 Reduces Inflammatory Cytokine Secretion in Caco-2 Cells Cultured in the Presence of Escherichia coli CECT 515.

Previous works have described the activity of Bifidobacterium longum subsp. infantis CECT 7210 (also commercially named B. infantis IM-1®) against rotavirus in mice and intestinal pathogens in piglets, as well as its diarrhea-reducing effect on healthy term infants. In the present work, we focused on the intestinal immunomodulatory effects of B. infantis IM-1® and for this purpose we used the epithelial cell line isolated from colorectal adenocarcinoma Caco-2 and a co-culture system of human dendritic cells (DCs) from peripheral blood together with Caco-2 cells. Single Caco-2 cultures and Caco-2: DC co-cultures were incubated with B. infantis IM-1® or its supernatant either in the presence or absence of Escherichia coli CECT 515. The B. infantis IM-1® supernatant exerted a protective effect against the cytotoxicity caused by Escherichia coli CECT 515 on single cultures of Caco-2 cells as viability reached the values of untreated cells. B. infantis IM-1® and its supernatant also decreased the secretion of pro-inflammatory cytokines by Caco-2 cells and the co-cultures incubated in the presence of E. coli CECT 515, with the response being more modest in the latter, which suggests that DCs modulate the activity of Caco-2 cells. Overall, the results obtained point to the immunomodulatory activity of this probiotic strain, which might underlie its previously reported beneficial effects.

Effect of Probiotics on Host-Microbiota in Bacterial Infections.

Diseases caused by bacteria cause millions of deaths every year. In addition, the problem of resistance to antibiotics is so serious that it threatens the achievements of modern medicine. This is a very important global problem as some bacteria can also develop persistence. Indeed, the persistence of pathogenic bacteria has evolved as a potent survival strategy to overcome host organisms' defense mechanisms. Additionally, chronic or persistent infections may be caused by persisters which could facilitate antibiotic resistance. Probiotics are considered good bacteria. It has been described that the modulation of gut microbiota by probiotics could have a great potential to counteract the deleterious impact and/or regulate gut microbiota after bacterial infection. Probiotics might provide health benefits through the inhibition of pathogen growth or the replacement of pathogenic bacteria. Bearing in mind that current strategies to avoid bacterial persistence and prevent antibiotic resistance are not effective, other strategies need to be assessed. We have carried out a comprehensive review, which included the reported literature between 2016 and 2021, highlighting the clinical trials that reported the probiotics' potential to regulate gut microbiota after bacterial infection and focusing in particular on the context of antibiotic resistance and persister cells.

Fiber Consumption Mediates Differences in Several Gut Microbes in a Subpopulation of Young Mexican Adults.

Diet is a determinant for bodyweight and gut microbiota composition. Changes in dietary patterns are useful for the prevention and management of overweight and obesity. We aim to evaluate diet behavior and its potential association with selected gut bacteria and body weight among Mexican young adults. Mexican college students aged between 18 and 25 (normal-weight, overweight, and obese) were recruited. Anthropometric variables were recorded. A validated food frequency questionnaire was applied to all the participants. The percentages of macronutrients, fiber, and energy were calculated, and fecal samples were analyzed by real-time-qPCR to quantify selected gut bacteria. All the participants showed an unbalanced dietary pattern. However, the consumption of fruits, non-fat cereals, and oils and fats without protein were higher in the normal-weight individuals. In the overweight/obese participants, fiber intake did not correlate with the microbial variables, while Kcal from protein and Clostridium leptum correlated positively with Lactobacillus. Similarly, Clostridium coccoides-Eubacterium rectale correlated with Akkermansia muciniphila. In the normal-weight participants, Clostridium leptum and Lactobacillus correlated positively with Clostridium coccoides-Eubacterium rectale and Bifidobacterium, respectively, and Bacteroidetes negatively with Akkermansia muciniphila. In conclusion, a higher fiber intake had a positive impact on body weight and bacterial gut composition in this Mexican population of college students.

Nutrition and cellular senescence in obesity-related disorders.

Adequate nutrition is vital for immune homeostasis. However, the incidence of obesity is increasing worldwide due to the adoption of the Western diet and a sedentary lifestyle. Obesity is associated with chronic inflammation which alters the function of adipose tissue, liver, pancreas, and the nervous system. Inflammation is related to cellular senescence, distinguished by irreversible cell cycle arrest. Senescent cells secrete the senescence-associated secretory phenotype (SASP) which contains pro-inflammatory factors. Targeting processes in senescence might have a salutary approach to obesity. The present review highlights the impact of an unhealthy diet on tissues affected by obesity, and the mechanisms that promote the consequent inflammation and senescence.