Microbial Translocation in the Context of Hepatitis B Infection and Hepatitis D Infection.

Background: Increased microbial translocation (MT) into the systemic circulation is associated with liver disease progression. Microbial translocation has yet to be completely defined in chronic hepatitis B virus (HBV) and chronic hepatitis delta virus (HDV). Methods: Our aim was to characterize MT and associated immune response in chronic HBV and HDV at various stages of disease. Serum from 53 HBV, 43 HDV, and 36 healthy control (HC) subjects was obtained. Subjects were categorized by aspartate aminotransferase-to-platelet ratio index into mild (<0.5), moderate, and severe (>1.0) disease. Cytokines, microbial products, and microbial deoxyribonucleic acid (DNA) levels were assessed in a single treatment-naive time point for each patient. Next-generation sequencing identified bacterial species present within patient sera. Results: The HBV and HDV subjects display higher serum concentrations of Gram-negative (G-) bacterial lipopolysaccharide and fungal beta-glucan compared with HC (all P < .01). Gram-positive (G+) bacterial peptidoglycan is higher in HBV compared to HDV and HC (both P < .0001). Within both disease cohorts, peptidoglycan correlates with interleukin (IL)-1b, IL-8, IL-12p70, and IL-13 (all Spearman's rho >0.45; P < .05). Next-generation sequencing from 7 subjects with detectable serum bacterial DNA revealed changes in abundance of bacterial taxa and a higher proportion of Gram-positive genera in severe disease. Greater G+/G- taxa ratio is associated with higher cytokine levels and disease markers. Conclusions: The HBV and HDV patients display increased translocation of bacterial and fungal products into serum. An increased proportion of Gram-positive genera is associated with disease progression. Correlations of peptidoglycan with antimicrobial cytokines suggest that particular microbial classes may contribute to systemic inflammation and possibly disease progression.

The balance of type 1 and type 2 immune responses in the contexts of hepatitis B infection and hepatitis D infection.

BACKGROUND AND AIM: Hepatitis delta virus (HDV) infection is the most rapidly progressive chronic viral hepatitis. Little is understood about the immune responses to HDV. This study aims to characterize the systemic immune environments of hepatitis B virus (HBV) and HDV patients at various disease stages. METHODS: A total of 129 subjects were evaluated: 53 HBV, 43 HDV, and 33 healthy controls. HBV and HDV subjects were categorized by aspartate aminotransferase to platelet ratio index (APRI) into mild (APRI < 0.5), moderate, and severe (APRI > 1.0). Serum cytokines and immune markers were assessed at a single treatment-naïve time-point. RESULTS: Type 1 cytokines are elevated in both HBV and HDV. Both groups show higher tumor necrosis factor-α (TNF-α), interleukin (IL)-12p40, and C-X-C motif chemokine ligand 9 when compared with controls (all P < 0.05). However, only HBV group displayed elevated γ-interferon compared with controls. Type 2 cytokines are elevated in HBV. HBV group shows higher IL-4, IL-13, and C-C motif chemokine ligand (CCL) 26 compared with healthy controls and HDV. Chemokines CCL2 and CCL13 are lower in HDV. When assessing ratios, HDV displays higher γ-interferon/IL-4, TNF-α/IL-4, and TNF-α/IL-13 ratios than HBV and controls. CONCLUSION: Hepatitis B virus and HDV subjects show similarly elevated type 1 cytokines. HDV subjects display relatively lower type 2 cytokines. These differences in the systemic immune environments, particularly the predominance of type 1 responses, may contribute to the comparatively rapid progression of HDV disease. Characterization of the imbalance in type 1 and type 2 immunity unique HDV has the potential to provide immunological insights for designing therapeutic targets in HDV-associated disease progression.

Risk-averse personalities have a systemically potentiated neuroendocrine stress axis: A multilevel experiment in Parus major.

Hormonal pleiotropy-the simultaneous influence of a single hormone on multiple traits-has been hypothesized as an important mechanism underlying personality, and circulating glucocorticoids are central to this idea. A major gap in our understanding is the neural basis for this link. Here we examine the stability and structure of behavioral, endocrine and neuroendocrine traits in a population of songbirds (Parus major). Upon identifying stable and covarying behavioral and endocrine traits, we test the hypothesis that risk-averse personalities exhibit a neuroendocrine stress axis that is systemically potentiated-characterized by stronger glucocorticoid reactivity and weaker negative feedback. We show high among-individual variation and covariation (i.e. personality) in risk-taking behaviors and demonstrate that four aspects of glucocorticoid physiology (baseline, stress response, negative feedback strength and adrenal sensitivity) are also repeatable and covary. Further, we establish that high expression of mineralocorticoid and low expression of glucocorticoid receptor in the brain are linked with systemically elevated plasma glucocorticoid levels and more risk-averse personalities. Our findings support the hypothesis that steroid hormones can exert pleiotropic effects that organize behavioral phenotypes and provide novel evidence that neuroendocrine factors robustly explain a large fraction of endocrine and personality variation.