Project description:Rationale: Recent studies suggest a potential link between gut bacterial microbiota dysbiosis and PAH, but the exact role of gut microbial communities, including bacteria, archaea, and fungi, in PAH remains unclear. Objectives: To investigate the role of gut microbiota dysbiosis in idiopathic pulmonary arterial hypertension (IPAH) and to assess the therapeutic potential of fecal microbiota transplantation (FMT) in modulating PAH progression. Methods: Using shotgun metagenomics, we analyzed gut microbial communities in IPAH patients and healthy controls. FMT was performed to transfer gut microbiota from IPAH patients or MCT-PAH rats to normal rats and from healthy rats to MCT-PAH rats. Hemodynamic measurements, echocardiography, histological examination, metabolomic and RNA-seq analysis were conducted to evaluate the effects of FMT on PAH phenotypes. Measurements and Main Results: Gut microbiota analysis revealed significant alterations in the bacterial, archaeal, and fungal communities in IPAH patients compared to healthy controls. FMT from IPAH patients induced PAH phenotypes in recipient rats. Conversely, FMT from healthy rats to IPAH rats significantly ameliorated PAH symptoms, restored gut microbiota composition, and normalized serum metabolite profiles. Specific microbial species were identified with high diagnostic potential for IPAH, improving predictive performance beyond individual or combined microbial communities. Conclusions: This study establishes a causal link between gut microbiota dysbiosis and IPAH and demonstrates the therapeutic potential of FMT in reversing PAH phenotypes. The findings highlight the critical role of bacterial, archaeal, and fungal communities in PAH pathogenesis and suggest that modulation of the gut microbiome could be a promising treatment strategy for PAH.
2025-04-30 | GSE271297 | GEO
Project description:Study of symbiotic gut bacteria across life stages and castes from 13 species of Cephalotes turtle ants
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.
Project description:In recent years, the scale culture of Chinese soft-shelled turtle has developed rapidly. However, diseases in aquaculture are the main problems affecting the rapid and healthy cultivation. Strengthening the immunity of Chinese soft-shelled turtles is extremely important to control the infection of pathogenic bacteria. Bacillus has attracted attention as a probiotic supplement in aquatic feeds.In our previous studies, we found that the addition of Bacillus subtilis B10 to diets could increase survival rate, daily weight gain (DG) and feed conversion ratio (FCR) of Chinese soft-shelled turtles, improving the activities of digestive enzyme and optimizing the microbial communities of intestinal in Chinese soft-shelled turtle.However, the study on the mechanism of Bacillus subtilis B10 in Chinese soft-shelled turtle culture remains rare. Therefore, in this study, we used Bacillus subtilis B10 to feed the turtle, and used RNA-seq to explore its mechanism.
Project description:Longitudinal studies of gut microbiota following specific interventions are vital for understanding how they influence host health. However, robust longitudinal sampling of gut microbial communities is a major challenge, which can be addressed using in vitro fermenters hosting complex microbial communities. Here, by employing 16S rRNA gene amplicon sequencing, we investigated the adaptation and succession of human fecal microbial communities in an automated in vitro fermenter. We performed two independent experiments each using a different human donor fecal sample – the first experiment was configured with two units of three colon compartments each studied for 22 days, and the second experiment with one unit of two colon compartments studied for 31 days. In both experiments, the fermenter maintained a trend of increasing microbial alpha-diversity along colon compartments, mimicking that of the human gastrointestinal tract. Within each experiment, microbial compositions followed compartment-specific trajectories over time and reached compartment-specific stable configurations. Microbial compositions were highly similar between the replicate units in the first experiment, thus showing reproducibility. Yet, microbial compositions and their trajectories were clearly separated between the two experiments, showing that these in vitro communities maintained the individuality of fecal inocula rather than converging on a fermenter-specific composition. Using longitudinal relative abundance profiles, we identified different dynamics exhibited by individual amplicon sequence variants (ASVs). While we could not detect some fecal ASVs in the in vitro communities, we observed that many ASVs undetected in the fecal sample flourished under in vitro conditions, which we named bloomers. In both experiments, bloomer ASVs accounted for significant proportions of ASV relative abundance after stabilization – 69% and 43% in the descending compartments in the two experiments. Bloomer ASVs included clinically relevant microbes associated with human health such as Bacteroides fragilis and Akkermansia muciniphila. This turnover in community compositions is likely explained by feed composition and pH, suggesting that these communities can be modulated. We characterized the exometabolites in the first experiment, derived a microbe-exometabolite bipartite network for its descending colon compartment, and identified 6 coherent groups based on the exometabolites. Our results suggest that in vitro fermenters are promising tools to study complex microbial communities harboring important members of human gut microbiota.
2021-07-15 | MTBLS2531 | MetaboLights
Project description:Honeybee bacterial community across gut compartments
Project description:The human gut is colonized by trillions of microorganisms that influence human health and disease through the metabolism of xenobiotics, including therapeutic drugs and antibiotics. The diversity and metabolic potential of the human gut microbiome have been extensively characterized, but it remains unclear which microorganisms are active and which perturbations can influence this activity. Here, we use flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the human gut contains distinctive subsets of active and damaged microorganisms, primarily composed of Firmicutes, which display marked temporal variation. Short-term exposure to a panel of xenobiotics resulted in significant changes in the physiology and gene expression of this active microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding novel candidate proteins for antibiotic resistance, drug metabolism, and stress response. These results demonstrate the power of moving beyond DNA-based measurements of microbial communities to better understand their physiology and metabolism. RNA-Seq analysis of the human gut microbiome during exposure to antibiotics and therapeutic drugs.
Project description:Mass spectrometry imaging is a powerful analytical technique for detecting and determining spatial distributions of molecules within a sample. Typically, mass spectrometry imaging is limited to the analysis of thin tissue sections taken from the middle of a sample. In this work, we present a mass spectrometry imaging method for the detection of compounds produced by bacteria on the outside surface of ant exoskeletons in response to pathogen exposure. Fungus-growing ants have a specialized mutualism with Pseudonocardia, a bacterium that lives on the ants’ exoskeletons and helps protect their fungal garden food source from harmful pathogens. The developed method allows for visualization of bacterial-derived compounds on the ant exoskeleton. This method demonstrates the capability to detect compounds that are specifically localized to the bacterial patch on ant exoskeletons, shows good reproducibility across individual ants, and achieves accurate mass measurements within 5 ppm error when using a high-resolution, accurate-mass mass spectrometer.