Collin L. Ellis

Molecular characterization of stool microbiota in HIV-infected subjects by panbacterial and order-level 16S ribosomal DNA (rDNA) quantification and correlations with immune activation.

Background:The relationship between gut microbial community composition at the higher-taxonomic order level and local and systemic immunologic abnormalities in HIV disease may provide insight into how bacterial translocation impacts HIV disease. Methods:Antiretroviral-naive patients with HIV underwent upper endoscopy before and 9 months after starting antiretroviral treatment. Duodenal tissue was paraffin-embedded for immunohistochemical analysis and digested for fluorescence activated cell sorting for T-cell subsets and immune activation (CD38+/HLA-DR+) enumeration. Stool samples were provided from patients and control subjects for comparison. Metagenomic microbial DNA was extracted from feces for optimized 16S ribosomal RNA gene (rDNA) real-time quantitative polymerase chain reaction assays designed to quantify panbacterial loads and the relative abundances of proinflammatory Enterobacteriales order and the dominant Bacteroidales and Clostridiales orders. Results:Samples from 10 HIV subjects before initiating and from six subjects receiving antiretroviral treatment were available for analysis. There was a trend for a greater proportion of Enterobacteriales in HIV-positive subjects compared with control subjects (P = 0.099). There were significant negative correlations between total bacterial load and duodenal CD4+ and CD8+ T-cell activation levels (r = −0.74, P = 0.004 and r = −0.67, P = 0.013, respectively). The proportions of Enterobacteriales and Bacteroidales were significantly correlated with duodenal CD4+ T-cell depletion and peripheral CD8+ T-cell activation, respectively. Conclusions:These data represent the first report of quantitative molecular and cellular correlations between total/universal and order-level gut bacterial populations and gastrointestinal-associated lymphoid tissue levels of immune activation in HIV-infected subjects. The correlations between lower overall 16S rDNA levels and tissue immune activation suggest that the gut microbiome may contribute to immune activation and influence HIV progression.

Guide to Designing, Conducting, Publishing, and Communicating Results of Clinical Studies Involving Probiotic Applications in Human Participants

The heterogeneity of human clinical trials to assess the effectiveness of probiotics presents challenges regarding interpretation and comparison. Evidence obtained from clinical trials among a population with disease or specific risk factors may not be generalizable to healthy individuals. The evaluation of interventions in healthy persons requires careful selection of outcomes due to the absence of health indicators and the low incidence of preventable conditions. Given the tremendous resources invested in such trials, development of consistent approaches to assessing the effectiveness of probiotics would be beneficial. Furthermore, the reporting, presentation, and communication of results may also affect the validity of the scientific evidence obtained from a trial. This review outlines the challenges associated with the design, implementation, data analysis, and interpretation of clinical trials in humans involving probiotics. Best practices related to their design are offered along with recommendations for enhanced collaboration to advance research in this emerging field.

HIV infection and atherosclerosis : evaluating the drivers of inflammation

As the population of people living with HIV ages, atherosclerotic cardiovascular disease (ASCVD) has become an increasing cause of morbidity and mortality. Traditional cardiovascular risk factors are common among those with HIV. In addition, some antiretroviral therapy (ART) regimens contribute to conditions such as hyperlipidemia and insulin resistance. However, inflammation is increasingly recognized as a key contributor to ASCVD. HIV infection induces immune activation and inflammation through several mechanisms. Co-infections such as hepatitis C and cytomegalovirus along with HIV itself likely initiate immune activation and inflammation. Translocation of bacterial products across a compromised epithelial barrier as a result of HIV infection is another mechanism by which the immune system is activated. In this article we summarize the current understanding of drivers of immune activation and inflammation among those with HIV and the contribution of each to ASCVD.

Probiotic administration in congenital heart disease: a pilot study

Objective:To investigate the impact of probiotic Bifidobacterium longum ssp. infantis on the fecal microbiota and plasma cytokines in neonates with congenital heart disease.Study design:Sixteen infants with congenital heart disease were randomly assigned to receive either B. infantis (4.2 × 109 colony-forming units two times daily) or placebo for 8 weeks. Stool specimens from enrolled infants and from six term infants without heart disease were analyzed for microbial composition. Plasma cytokines were analyzed weekly in the infants with heart disease.Results:Healthy control infants had increased total bacteria, total Bacteroidetes and total bifidobacteria compared to the infants with heart disease, but there were no significant differences between the placebo and probiotic groups. Plasma interleukin (IL)10, interferon (IFN)γ and IL1β levels were transiently higher in the probiotic group.Conclusion:Congenital heart disease in infants is associated with dysbiosis. Probiotic B. infantis did not significantly alter the fecal microbiota. Alterations in plasma cytokines were found to be inconsistent.

Intestinal microbiota and blue baby syndrome: probiotic therapy for term neonates with cyanotic congenital heart disease.

Necrotizing enterocolitis (NEC) is the most common intestinal emergency among premature infants. Risk factors in premature infants include immature intestinal immunity and an intestinal microbiota dominated by hospital-acquired bacteria. Some probiotics have been shown to decrease the incidence of NEC in premature infants. Among term infants, NEC is rare. However, among term infants with cyanotic congenital heart disease (CCHD), the incidence of NEC is similar to that of premature infants but with even greater mortality rates. Mechanisms by which NEC occurs in term infants with CCHD are unknown. Of central interest is the potential role of changes in the intestinal microbiota and whether these can be modified with probiotic bacteria; accordingly, we review the literature, propose hypotheses, and present the rationale for future studies involving preliminary probiotic clinical trials.

W1830 CD4+ T-Cell Depletion in Gut-Associated Lymphoid Tissue and CD8+ T-Cell Hyperactivation in Peripheral Blood are Linked to Greater Gut-Proportion of Enterobacteriales and Bacteroidales in HIV Therapy Pre-Clinical Trial Analysis

thy) and histologic (epithelial erosions, crypt hyperplasia, mononuclear cellular infiltrate) lesions were inversely associated with changes in composition of the intestinal microbiota of IL-10-/mice at all time points. Conclusions: Changes in the relative densities and spatial distribution of dominant bacterial groups occur and precede the development of colitis in IL-10-/mice. Archaea decreased in colitic IL-10-/mice and appear to associate with different bacterial species during active inflammation. These results indicate that the Archaea (methanogens) may serve as a biomarker for onset and progression of IBD. Further work on the diversity of methanogens as well as alterations in the concentration of methanogenic species is required to fully assess their biomarker potential.