Project description:Aging is associated with declining immunity and inflammation as well as alterations in the gut microbiome with a decrease of beneficial microbes and increase in pathogenic ones. The aim of this study was to investigate aging associated gut microbiome in relation to immunologic and metabolic profile in a non-human primate (NHP) model. 12 old (age>18 years) and 4 young (age 3-6 years) Rhesus macaques were included in this study. Immune cell subsets were characterized in PBMC by flow cytometry and plasma cytokines levels were determined by bead based multiplex cytokine analysis. Stool samples were collected by ileal loop and investigated for microbiome analysis by shotgun metagenomics. Serum, gut microbial lysate and microbe-free fecal extract were subjected to metabolomic analysis by mass-spectrometry. Our results showed that the old animals exhibited higher inflammatory biomarkers in plasma and lower CD4 T cells with altered distribution of naïve and memory T cell maturation subsets. The gut microbiome in old animals had higher abundance of Archaeal and Proteobacterial species and lower Firmicutes than the young. Significant enrichment of metabolites that contribute to inflammatory and cytotoxic pathways was observed in serum and feces of old animals compared to the young. We conclude that aging NHP undergo immunosenescence and age associated alterations in the gut microbiome that has a distinct metabolic profile.
Project description:Caves are populated with a diverse fauna of highly adapted species that tend to exhibit a consistent suite of both regressive and constructive trait modifications. Because molecular studies of cave adaptation have largely concentrated on vertebrate models, our ability to recognize universalities in the genetic trajectories underlying cave adaptation remains limited. We have initiated efforts to elucidate the molecular evolution of the flightless small carrion beetle Ptomaphagus hirtus (Ptomaphagus hirtus), which represents one of the highly endemic signature inhabitants of the Mammoth Cave system of Kentucky. Ptomaphagus hirtus has been considered blind despite the presence of lateral eye rudiments. However, analysis of the Ptomaphagus hirtus adult head transcriptome by deep RNA sequencing reveals the conservation and expression of all essential insect phototransduction genes including a single long wavelength-sensitive opsin. Consistent with the preservation of visual ability, Ptomaphagus hirtus expresses all core members of the clock gene network and exhibits a similar degree of negative phototaxis as does a closely related flight-active species in light-dark choice assays. The structural reduction of the peripheral Ptomaphagus hirtus visual system is reflected by the lack of five eye pigmentation specific genes in the head transcriptome. Taken together our data suggest that wavelength contingent and probably also spatial vision have been lost in Ptomaphagus hirtus, while irradiance vision and contingent behavioral modules have remained preserved. We predict that the adaptive state of Ptomaphagus hirtus is representative for a large number of microphthalmic species adapted to the twilight zone of caves and other subterranean habitats Poly(A)+ transcripts were isolated from a pooled sample of 25 adult Ptomaphagus hirtus heads, reverse transcribed and sequenced on the Illumina GAII
Project description:Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit long term use. In the current study using a chronic morphine-murine model a longitudinal approach was undertaken to investigate the role of morphine modulation of gut microbiome as a mechanism contributing to the negative consequences associated with opioids use. The results revealed a significant shift in the gut microbiome and metabolome within 24 hours following morphine treatment when compared to placebo. Morphine induced gut microbial dysbiosis exhibited distinct characteristic signatures profiles including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance. Collectively, these results reveal opioids-induced distinct alteration of gut microbiome, may contribute to opioids-induced pathogenesis. Therapeutics directed at these targets may prolong the efficacy long term opioid use with fewer side effects.