Project description:Fermenting microbial communities generate hydrogen: its removal through production of acetate, methane, or hydrogen sulfide modulates the efficiency of energy extraction from available nutrients in many ecosystems. We noted that pathway components for acetogenesis are more abundantly and consistently represented in the gut microbiomes of monozygotic twins and their mothers than components for methanogenesis or sulfate reduction, and subsequently analyzed the metabolic potential of two sequenced human gut acetogens, Blautia hydrogenotrophica and Marvinbryantia formatexigens in vitro and in the intestines of gnotobiotic mice harboring a prominent saccharolytic bacterium. To do so, we developed a generally applicable method for multiplex sequencing of expressed microbial mRNAs, and together with mass spectrometry of metabolites, show that these organisms have distinct patterns of substrate utilization. B. hydrogenotrophica targets aliphatic and aromatic amino acids. It increases the efficiency of fermentation by consuming reducing equivalents, thereby maintaining a high NAD+/NADH ratio and boosting acetate production. In contrast, M. formatexigens consumes oligosaccharides, does not impact the redox state of the gut, and boosts the yield of succinate. These findings have strategic implications for those who wish to manipulate the hydrogen economy of gut microbial communities in ways that modulate energy harvest. 119 Samples consisting of Bacteroides thetaiotaomicron, Marvinbryantia formatexigens, and Blautia hydrogenotrophica cecal and fecal samples. Please see the individual Sample descriptions for more information.
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:Fermenting microbial communities generate hydrogen: its removal through production of acetate, methane, or hydrogen sulfide modulates the efficiency of energy extraction from available nutrients in many ecosystems. We noted that pathway components for acetogenesis are more abundantly and consistently represented in the gut microbiomes of monozygotic twins and their mothers than components for methanogenesis or sulfate reduction, and subsequently analyzed the metabolic potential of two sequenced human gut acetogens, Blautia hydrogenotrophica and Marvinbryantia formatexigens in vitro and in the intestines of gnotobiotic mice harboring a prominent saccharolytic bacterium. To do so, we developed a generally applicable method for multiplex sequencing of expressed microbial mRNAs, and together with mass spectrometry of metabolites, show that these organisms have distinct patterns of substrate utilization. B. hydrogenotrophica targets aliphatic and aromatic amino acids. It increases the efficiency of fermentation by consuming reducing equivalents, thereby maintaining a high NAD+/NADH ratio and boosting acetate production. In contrast, M. formatexigens consumes oligosaccharides, does not impact the redox state of the gut, and boosts the yield of succinate. These findings have strategic implications for those who wish to manipulate the hydrogen economy of gut microbial communities in ways that modulate energy harvest.
Project description:Exploring dietary methods to alter microbial communities and metabolic functions is becoming an increasingly fascinating strategy for improving health. Copra meal hydrolysate (CMH) is commonly used as a gut health supplement. However, the functional diversity and metabolic activities in gut microbiome in relation to CMH treatment remain largely unknown.
Project description:Here we map the molecular response of a synthetic community of 32 human gut bacteria to three non-antibiotic drugs by using five omics layers, namely 16S rRNA gene profiling, metagenomics, metatranscriptomics, metaproteomics, and metabolomics. Using this controlled setting, we find that all omics methods with species resolution in their readouts are highly consistent in estimating relative species abundances across conditions. Furthermore, different omics methods can be complementary in their ability to capture functional changes in response to the drug perturbations. For example, while nearly all omics data types captured that the antipsychotic drug chlorpromazine selectively inhibits Bacteroidota representatives in the community, the metatranscriptome and metaproteome suggested that the drug induces stress responses related to protein quality control and metabolomics revealed a decrease in polysaccharide uptake, likely caused by Bacteroidota depletion. Taken together, our study provides insights into how multi-omics datasets can be utilised to reveal complex molecular responses to external perturbations in microbial communities.