Agricultural Dust Derived Bacterial Extracellular Vesicle Mediated Inflammation is Attenuated by DHA

Dietary long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and their pro-resolving metabolites are protective against atherosclerotic disease, and ameliorate systemic inflammatory conditions including lupus erythematosus, psoriasis, and bronchial asthma. Organic bioaerosol inhalation is a common and injurious hazard associated with agricultural occupations such as work in swine concentrated animal feeding operations (CAFOs) and is known to increase the risk for developing respiratory conditions such as asthma and COPD. Nearly all cells secrete membrane-bound vesicles (extracellular vesicles, EVs) that have the capacity to transmit protein, nucleic acid, and lipid signaling mediators between cells. Using a polymer-based isolation technique (ExoQuick, PEG) followed by ultracentrifugation, EVs were isolated from CAFO dust extracts, and were quantified and partially characterized. Here, we investigated the role of the n-3 PUFA docosahexaenoic acid (DHA) as a component of n-6 to n-3 PUFA mixtures used to recapitulate physiologically relevant dietary ratios in the resolution of inflammatory injury caused by exposure to EVs carried by agricultural organic dust in vitro. Primary human bronchial epithelial cells, fibroblasts and monocyte-derived macrophages were exposed to EVs isolated from swine CAFO dust. Cells were treated with mixtures of n-6 and n-3 PUFA during recovery from the EV-induced injury. CAFO dust extract (DE) was found to contain EVs that contributed significantly to the overall consequences of exposure to complete DE. DHA-rich PUFA ratios inhibited DE-derived EV-induced proinflammatory cytokine release dose-dependently. DHA-rich PUFA ratios also reversed the damaging effects of EVs on recellularization of lung matrix scaffolds, accelerated wound healing, and stimulated the release of pro-resolution mediators. These results underscore the importance of n-3 PUFA as anti-inflammatory compounds during recovery from EV-laden environmental dust exposure in the context of cellular responses in vitro, warranting future translational studies

Natural killer cell effector function is critical for host defense against alcohol-associated bacterial pneumonia

Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon receptor (AhR) signaling. Employing a binge-on-chronic alcohol-feeding model we sought to define the role and interaction of indole and NK cells during pulmonary host defense against alcohol-associated pneumonia. We demonstrate that alcohol dysregulates NK cell effector function and pulmonary recruitment via alterations in two key signaling pathways. We found that alcohol increases transforming growth factor beta (TGF-β) signaling while suppressing AhR signaling. We further demonstrated that NK cells isolated from alcohol-fed mice have a reduced ability to kill Klebsiella pneumoniae. NK cell migratory capacity to chemokines was also significantly altered by alcohol, as NK cells isolated from alcohol-fed mice exhibited preferential migration in response to CXCR3 chemokines but exhibited reduced migration in response to CCR2, CXCR4, and CX3CR1 chemokines. Together this data suggests that alcohol disrupts NK cell-specific TGF-β and AhR signaling pathways leading to decreased pulmonary recruitment and cytolytic activity thereby increasing susceptibility to alcohol-associated bacterial pneumonia

Discovery of a dopamine producing microbe in the gut: Implications for animal and human health as well as industrial applications.

Though scientists have discussed the health impact of the gut flora for over a century, technological advancement, and discoveries in the fields of microbiology, immunology, endocrinology and neurobiology have dramatically changed the way we understand the microbiota. We have come to realize that microbes are part of complex multispecies communities that exist as important symbionts. Within the context of the mammalian gut, the microbiota can be likened to a distinct part of a neuro-endocrine axis. Through actions on the neuroendocrine axes of the body, the microbiota influences host behavior and health. The body of this dissertation, which consists of research in the field of microbial endocrinology, provides a glimpse into the complex ways in which the host and microbiota interact in this manner. The primary objective of the dissertation is to provide a context by which one can understand the importance of a dopamine producing gut microbe. In compiling this research, the author hopes that one may walk away with a new insight into how the microbiota can modulate host health by the production of neurochemicals.</p

Discovery of a dopamine producing microbe in the gut: Implications for animal and human health as well as industrial applications.

Though scientists have discussed the health impact of the gut flora for over a century, technological advancement, and discoveries in the fields of microbiology, immunology, endocrinology and neurobiology have dramatically changed the way we understand the microbiota. We have come to realize that microbes are part of complex multispecies communities that exist as important symbionts. Within the context of the mammalian gut, the microbiota can be likened to a distinct part of a neuro-endocrine axis. Through actions on the neuroendocrine axes of the body, the microbiota influences host behavior and health. The body of this dissertation, which consists of research in the field of microbial endocrinology, provides a glimpse into the complex ways in which the host and microbiota interact in this manner. The primary objective of the dissertation is to provide a context by which one can understand the importance of a dopamine producing gut microbe. In compiling this research, the author hopes that one may walk away with a new insight into how the microbiota can modulate host health by the production of neurochemicals

Discovery of a dopamine producing microbe in the gut: Implications for animal and human health as well as industrial applications.

Though scientists have discussed the health impact of the gut flora for over a century, technological advancement, and discoveries in the fields of microbiology, immunology, endocrinology and neurobiology have dramatically changed the way we understand the microbiota. We have come to realize that microbes are part of complex multispecies communities that exist as important symbionts. Within the context of the mammalian gut, the microbiota can be likened to a distinct part of a neuro-endocrine axis. Through actions on the neuroendocrine axes of the body, the microbiota influences host behavior and health. The body of this dissertation, which consists of research in the field of microbial endocrinology, provides a glimpse into the complex ways in which the host and microbiota interact in this manner. The primary objective of the dissertation is to provide a context by which one can understand the importance of a dopamine producing gut microbe. In compiling this research, the author hopes that one may walk away with a new insight into how the microbiota can modulate host health by the production of neurochemicals