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:The gut microbiota impacts many aspects of host biology including immune function. One hypothesis is that microbial communities induce epigenetic changes with accompanying alterations in chromatin accessibility, providing a mechanism that allows a community to have sustained host effects even in the face of its structural or functional variation. We used ATAC-seq to define chromatin accessibility in predicted enhancer regions of intestinal αβ+ and γδ+ intraepithelial lymphocytes (IELs) purified from germ-free mice, their conventionally-raised (CONV-R) counterparts, and mice reared GF and then colonized with a CONV-R gut microbiota at the end of the suckling-weaning transition. Characterizing genes adjacent to traditional enhancers and super-enhancers revealed signaling networks, metabolic pathways, and enhancer-associated transcription factors affected by the microbiota. Our results support the notion that epigenetic modifications help define microbial community-affiliated functional features of host immune cell lineages.
Project description:Fire is a crucial event regulating the structure and functioning of many ecosystems. Yet few studies focused on how fire affects both the taxonomic and functional diversity of soil microbial communities, along with plant diversity and soil carbon (C) and nitrogen (N) dynamics. Here, we analyze these effects for a grassland ecosystem 9-months after an experimental fire at the Jasper Ridge Global Change Experiment (JRGCE) site in California, USA. Fire altered soil microbial communities considerably, with community assembly process analysis indicating that environmental selection pressure was higher in burned sites. However, a small subset of highly connected taxa were able to withstand the disturbance. In addition, fire decreased the relative abundances of most genes associated with C degradation and N cycling, implicating a slow-down of microbial processes linked to soil C and N dynamics. In contrast, fire stimulated plant growth, likely enhancing plant-microbe competition for soil inorganic N. To synthesize our findings, we performed structural equation modeling, which showed that plants but not microbial communities were responsible for the significantly higher soil respiration rates in burned sites. In conclusion, fire is well-documented to considerable alter the taxonomic and functional composition of soil microorganisms, along with the ecosystem functioning, thus arousing feedback of ecosystem responses to affect global climate.