Distinct fecal microbial signatures are linked to sex and chronic immune activation in pediatric HIV infection.

Introduction: Our understanding of HIV-associated gut microbial dysbiosis in children perinatally-infected with HIV (CLWH) lags behind that of adults living with HIV. Childhood represents a critical window for the gut microbiota. Any disturbances, including prolonged exposure to HIV, antiretroviral drugs, and antibiotics are likely to have a significant impact on long-term health, resulting in a less resilient gut microbiome. The objective of our study was to characterize the gut microbiota in CLWH, and compare it with HIV-unexposed and -uninfected children. Methods: We enrolled 31 children aged 3 to 15 years; 15 were CLWH and 16 were HUU. We assessed dietary patterns and quality; quantified soluble and cellular markers of HIV disease progression by flow cytometry, enzyme-linked immunosorbent and multiplex-bead assays, and profiled the gut microbiota by 16S rRNA sequencing. We explored relationships between the gut microbiota, antibiotic exposure, dietary habits, soluble and cellular markers and host metadata. Results: Children had a Western-type diet, their median health eating index score was 67.06 (interquartile range 58.76-74.66). We found no discernable impact of HIV on the gut microbiota. Alpha diversity metrics did not differ between CLWH and HUU. Sex impacted the gut microbiota (R-squared= 0.052, PERMANOVA p=0.024). Male children had higher microbial richness compared with female children. Two taxa were found to discriminate female from male children independently from HIV status: Firmicutes for males, and Bacteroides for females. Markers of HIV disease progression were comparable between CLWH and HUU, except for the frequency of exhausted CD4+ T cells (PD-1+) which was increased in CLWH (p=0.0024 after adjusting for confounders). Both the frequency of exhausted CD4+ and activated CD4+ T cells (CD38+ HLADR+) correlated positively with the relative abundance of Proteobacteria (rho=0.568. false discovery rate (FDR)-adjusted p= 0.029, and rho=0.62, FDR-adjusted p=0.0126, respectively). Conclusion: The gut microbiota of CLWH appears similar to that of HUU, and most markers of HIV disease progression are normalized with long-term ART, suggesting a beneficial effect of the latter on the gut microbial ecology. The relationship between exhausted and activated CD4+ T cells and Proteobacteria suggests a connection between the gut microbiome, and premature aging in CLWH.

Therapeutic avenues for restoring the gut microbiome in HIV infection.

The interplay between the gut microbiota, the intestinal barrier and the mucosal immune system is profoundly altered in Human Immunodeficiency Virus (HIV) infection. An HIV-associated microbial dysbiotic signature has been difficult to define due to the strong impact of confounders that are intimately linked with HIV infection, namely HIV risk behaviors. When controlling for sexual preference and gender, HIV-associated microbial dysbiotic signatures are characterized by an increase in deleterious taxa and a decrease in beneficial bacteria and their respective metabolic end-products. First attempts to restore the gut microbiota of HIV subjects on Antiretroviral Therapy using Fecal Microbiota Transplantation proved to be safe and reported mild transient engraftment of donor microbiota and no effect on markers of HIV disease progression. This review focuses on the current evidence supporting a role for microbial dysbiosis in HIV pathogenesis, and reviews current microbiome-based therapeutics for restoring the gut microbiota in HIV infection.

Simultaneous evaluation of metabolomic and inflammatory biomarkers in children with different body mass index (BMI) and waist-to-height ratio (WHtR).

Metabolic disturbances and systemic pro-inflammatory changes have been reported in children with obesity. However, it is unclear the time-sequence of metabolic or inflammatory modifications during children obesity evolution. Our study aimed to quantify simultaneously metabolomic and inflammatory biomarkers in serum from children with different levels of adiposity. For this purpose, a cross-sectional study was used to perform targeted metabolomics and inflammatory cytokines measurements. Serum samples from children between six to ten years old were analyzed using either body mass index (BMI) or waist-to-height ratio (WHtR) classifications. One hundred and sixty-eight school-aged children were included. BMI classification in children with overweight or obesity showed altered concentrations of glucose and amino acids (glycine and tyrosine). Children classified by WHtR exhibited imbalances in amino acids (glycine, valine, and tyrosine) and lipids (triacyl glycerides and low-density lipoprotein) compared to control group. No differences in systemic inflammation biomarkers or in the prevalence of other results were found in these children. Abnormal arterial blood pressure was found in 32% of children with increased adiposity. In conclusion, obesity in school-aged children is characterized by significant metabolic modifications that are not accompanied by major disturbances in circulating concentrations of inflammatory biomarkers.

An intervention to promote physical activity in Mexican elementary school students: building public policy to prevent noncommunicable diseases.

Physical activity is an important component of strategies for health promotion and prevention of noncommunicable diseases. It is also associated with decreased risk for cardiovascular disease in overweight and obese adults and children. This article addresses the initial description of a physical activity intervention for children attending public elementary schools in Mexico. The objective was to develop a replicable model based on a strategic public, private, academic, and social partnership that would have a short-term impact on the metabolic health of children and be useful for building effective public policy. Forty-nine schools (20 000 students) participated, and 5 schools were selected for evaluation. The intervention included a 30-minute supervised middle-effort interchangeable routine, 5 days a week for a complete school year, adapted for different school conditions and students of different ages. Evaluation included anthropometric measurements and biochemical markers. Actual prevalence of combined overweight and obesity in these children was 31.9%. The intervention was successfully implemented in all schools. No change in body mass index, waist circumference, or other anthropometric indicators was found. However, changes in biochemical markers showed a significant decrease in blood glucose, total cholesterol, and cholesterol-low-density lipoproteins, reflecting a positive effect on cardiovascular health indicators.

[PCR detection of relevant translocations in pediatric acute lymphoblastic leukemia]. / Detección de translocaciones relevantes por PCR en pacientes pediátricos con leucemia linfoblástica aguda.

BACKGROUND: In Mexico, leukemia represents the most common type of cancer in the population under 15 years old with a high incidence rate when compared with developed countries. The etiology of leukemia may be unknown, however different factors are involve such as chromosomal translocations. The aim of this work is to detect the molecular alterations: TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1 in pediatric patients with acute lymphoblastic leukemia. METHODS: 91 bone marrow samples were collected from pediatric patients with acute lymphoblastic leukemia from january 2012 to march 2013 at the Pediatric Hematology Service, Hospital General "Gaudencio González Garza". Translocations detected (TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1) using real time PCR, SYBR Green (Qiagen, Alameda, CA). RESULTS: 91 samples were processed, the detected frequencies for each translocation were: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). The MLL-AF4 and the BCR-ABL minor translocations were not detected in this study. CONCLUSIONS: The frequencies shown in this study are consistent with the data shown in the literature, where TEL-AML1 is the most common translocation found in pediatric patients. It is of relevance to mention that E2A-PBX1 is found in a high frequency in developing countries when compared with developed countries.

Introducción: en México, las leucemias representan el tipo de cáncer más frecuente en la población menor de 15 años con una tasa de incidencia alta cuando se compara con países desarrollados. La etiología de las leucemias puede ser desconocida, sin embargo se presentan distintos factores que pueden condicionar la enfermedad, tal es el caso de las translocaciones cromosómicas. El objetivo de este trabajo es detectar las alteraciones moleculares: TEL-AML1, MLL-AF4, BCR-ABL menor y E2A-PBX1 en los pacientes pediátricos con leucemia aguda linfoblástica. Métodos: se colectaron 91 muestras de médula ósea de enero de 2012 a marzo de 2013 de pacientes pediátricos con leucemia aguda linfoblástica del Servicio de Hematología. Se detectaron las translocaciones (TEL-AML1, MLL-AF4, BCR-ABL menor y E2A-PBX1) con técnicas moleculares de tiempo real con SYBR Green (Qiagen, Alameda, CA). Resultados: se procesaron 91 muestras, las frecuencias detectadas para cada una de las translocaciones fueron: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). Las translocaciones MLL-AF4 y BCR-ABL menor no fueron detectadas en este estudio. Conclusiones: las frecuencias mostradas en este estudio están en concordancia con los datos mostrados en la literatura donde TEL-AML1 es la translocación más común encontrada en pacientes pediátricos. Es importante mencionar que E2A-PBX1 se encuentra en una frecuencia alta en países en vías de desarrollo al comparase con países desarrollados.