Integrative analysis of systemic lupus erythematosus biomarkers: Role of fecal hsa-mir-223-3p and gut microbiota in transkingdom dynamics.

Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223-3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value <0.05) and core microbiome between cases and controls. In addition, Collinsella, Bifidobacterium, Streptococcus genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223-3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p<0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.

Functional imaging and anatomical connections in squirrel monkeys reveal parietal-frontal circuits underlying eye movements.

The posterior parietal cortex (PPC) of squirrel monkeys contains subregions where long trains of intracortical microstimulation evoke complex, behaviorally meaningful movements. Recently, we showed that such stimulation of a part of the PPC in the caudal lateral sulcus (LS) elicits eye movements in these monkeys. Here, we studied the functional and anatomical connections of this oculomotor region we call parietal eye field (PEF) with frontal eye field (FEF) and other cortical regions in 2 squirrel monkeys. We demonstrated these connections with intrinsic optical imaging and injections of anatomical tracers. Optical imaging of frontal cortex during stimulation of the PEF evoked focal functional activation within FEF. Tracing studies confirmed the functional PEF-FEF connections. Moreover, tracer injections revealed PEF connections with other PPC regions on the dorsolateral and medial brain surface, cortex in the caudal LS, and visual and auditory cortical association areas. Subcortical projections of PEF were primarily with superior colliculus, and pontine nuclei as well as nuclei of the dorsal posterior thalamus and caudate. These findings suggest that PEF in squirrel monkey is homologous to lateral intraparietal (LIP) area of macaque, supporting the notion that these brain circuits are organized similarly to mediate ethologically relevant oculomotor behaviors.

Comprehensive Phenotyping in Inflammatory Bowel Disease: Search for Biomarker Algorithms in the Transkingdom Interactions Context.

Inflammatory bowel disease (IBD) is the most common form of intestinal inflammation associated with a dysregulated immune system response to the commensal microbiota in a genetically susceptible host. IBD includes ulcerative colitis (UC) and Crohn's disease (CD), both of which are remarkably heterogeneous in their clinical presentation and response to treatment. This translates into a notable diagnostic challenge, especially in underdeveloped countries where IBD is on the rise and access to diagnosis or treatment is not always accessible for chronic diseases. The present work characterized, for the first time in our region, epigenetic biomarkers and gut microbial profiles associated with UC and CD patients in the Buenos Aires Metropolitan area and revealed differences between non-IBD controls and IBD patients. General metabolic functions associated with the gut microbiota, as well as core microorganisms within groups, were also analyzed. Additionally, the gut microbiota analysis was integrated with relevant clinical, biochemical and epigenetic markers considered in the follow-up of patients with IBD, with the aim of generating more powerful diagnostic tools to discriminate phenotypes. Overall, our study provides new insights into data analysis algorithms to promote comprehensive phenotyping tools using quantitative and qualitative analysis in a transkingdom interactions network context.

A Two-Time Point Analysis of Gut Microbiota in the General Population of Buenos Aires and Its Variation Due to Preventive and Compulsory Social Isolation During the COVID-19 Pandemic.

The COVID-19 pandemic poses a great challenge to global public health. The extraordinary daily use of household disinfectants and cleaning products, social distancing and the loss of everyday situations that allow contact between individuals, have a direct impact on the transfer of microorganisms within the population. Together, these changes, in addition to those that occur in eating habits, can affect the composition and diversity of the gut microbiota. A two-time point analysis of the fecal microbiota of 23 Metropolitan Buenos Aires (BA) inhabitants was carried out, to compare pre-pandemic data and its variation during preventive and compulsory social isolation (PCSI) in 2020. To this end, 23 healthy subjects, who were previously studied by our group in 2016, were recruited for a second time during the COVID-19 pandemic, and stool samples were collected from each subject at each time point (n = 46). The hypervariable region V3-V4 of the 16S rRNA gene was high-throughput sequenced. We found significant differences in the estimated number of observed features (p < 0.001), Shannon entropy index (p = 0.026) and in Faith phylogenetic diversity (p < 0.001) between pre-pandemic group (PPG) vs. pandemic group (PG), being significantly lower in the PG. Although no strong change was observed in the core microbiota between the groups in this study, a significant decrease was observed during PCSI in the phylum Verrucomicrobia, which contributes to intestinal health and glucose homeostasis. Microbial community structure (beta diversity) was also compared between PPG and PG. The differences observed in the microbiota structure by unweighted UniFrac PCoA could be explained by six differential abundant genera that were absent during PCSI. Furthermore, putative functional genes prediction using PICRUSt infers a smaller predicted prevalence of genes in the intestinal tryptophan, glycine-betaine, taurine, benzoate degradation, as well as in the synthesis of vitamin B12 during PCSI. This data supports the hypothesis that the microbiome of the inhabitants of BA changed in the context of isolation during PCSI. Therefore, these results could increase the knowledge necessary to propose strategic nutraceutical, functional food, probiotics or similar interventions that contribute to improving public health in the post-pandemic era.

Getting to Know the Gut Microbial Diversity of Metropolitan Buenos Aires Inhabitants.

In recent years, the field of immunology has been revolutionized by the growing understanding of the fundamental role of microbiota in the immune system function. The immune system has evolved to maintain a symbiotic relationship with these microbes. The aim of our study was to know in depth the uncharacterized metagenome of the Buenos Aires (BA) city population and its metropolitan area, being the second most populated agglomeration in the southern hemisphere. For this purpose, we evaluated 30 individuals (age: 35.23 ± 8.26 years and BMI: 23.91 ± 3.4 kg/m2), from the general population of BA. The hypervariable regions V3-V4 of the bacterial 16S gene was sequenced by MiSeq-Illumina system, obtaining 47526 ± 4718 sequences/sample. The dominant phyla were Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia, and Actinobacteria. Additionally, we compared the microbiota of BA with other westernized populations (Santiago de Chile, Rosario-Argentina, United States-Human-microbiome-project, Bologna-Italy) and the Hadza population of hunter-gatherers. The unweighted UniFrac clustered together all westernized populations, leaving the hunter-gatherer population from Hadza out. In particular, Santiago de Chile's population turns out to be the closest to BA's, principally due to the presence of Verrucomicrobiales of the genus Akkermansia. These microorganisms have been proposed as a hallmark of a healthy gut. Finally, westernized populations showed more abundant metabolism related KEEG pathways than hunter-gatherers, including carbohydrate metabolism (amino sugar and nucleotide sugar metabolism), amino acid metabolism (alanine, aspartate and glutamate metabolism), lipid metabolism, biosynthesis of secondary metabolites, and sulfur metabolism. These findings contribute to promote research and comparison of the microbiome in different human populations, in order to develop more efficient therapeutic strategies for the restoration of a healthy dialogue between host and environment.

Determinación de Inmunoglobulina A en Leche Materna en Los Quince Días Posparto

El presente estudio se realizó con el objetivo de cuantificar la concentración de inmunoglobulina A en leche materna durante los quince días posparto, abarcando así las tres fases de lactancia: calostro, transición y madura. El diseño de investigación fue observacional, descriptivo de corte transversal; en un total de 5 madres voluntarias con parto a término y en periodo de lactancia que ingresaron con un embarazo mayor de 38 semanas con diagnóstico de labor de parto a la Fundación Humanitaria "Pablo Jaramillo Crespo". Las muestras de leche materna fueron recolectadas durante puerperio inmediato (24 horas) hasta puerperio mediato (2 semanas). Se procesaron setenta y cinco muestras de leche materna por duplicado de 5 madres en periodo de lactancia; determinándose la concentración de IgA secretora mediante la técnica de Inmunodifusión radial (IDR). Se comprobó que la IgA presenta su máxima concentración el primer día del postparto (407,47 mg/dL), si comparamos con el décimo quinto día, donde el volumen de leche es mayor pero posee menor concentración de IgA (55,93 mg/dL); presentando la información mediante el diagrama de casos. Además se realizó un análisis estadístico ANOVA para las variables de la paridad y el tipo de parto, los resultados arrojados indican que ninguna de las dos variables influyen en la concentración de la IgA durante los 15 días postparto; paridad (p= 0.432), y tipo de parto (p= 0.842).

The present study has been done in order to quantify the concentration of immunoglobulin A in breast milk during the fifteen days postpartum, consequently covering the three phases of lactation: colostrum, transitional and mature. The research design through observation and cross sectional descriptive, in five volunteer mothers who delivered at term and nursing diagnosis admitted with labor and pregnancy over 38 weeks at the Foundation Humanitarian "Pablo Jaramillo Crespo" Hospital. The present study has been done in order to quantify the concentration of immunoglobulin A in breast milk during the fifteen days postpartum, consequently covering the three phases of lactation: colostrum, transitional and mature. The research design through observation and cross sectional descriptive, in five volunteer mothers who delivered at term and nursing diagnosis admitted with labor and pregnancy over 38 weeks at the Foundation Humanitarian "Pablo Jaramillo Crespo" Hospital.