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Cancer Cell Feb 2022Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation, tumor growth, and therapy response. Gut microbes signal via metabolites, but...
Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation, tumor growth, and therapy response. Gut microbes signal via metabolites, but how the metabolites impact CRC is largely unknown. We interrogated fecal metabolites associated with mouse models of colon tumorigenesis with varying mutational load. We find that microbial metabolites from healthy mice or humans are growth-repressive, and this response is attenuated in mice and patients with CRC. Microbial profiling reveals that Lactobacillus reuteri and its metabolite, reuterin, are downregulated in mouse and human CRC. Reuterin alters redox balance, and reduces proliferation and survival in colon cancer cells. Reuterin induces selective protein oxidation and inhibits ribosomal biogenesis and protein translation. Exogenous Lactobacillus reuteri restricts colon tumor growth, increases tumor reactive oxygen species, and decreases protein translation in vivo. Our findings indicate that a healthy microbiome and specifically, Lactobacillus reuteri, is protective against CRC through microbial metabolite exchange.
Topics: Animals; Biomarkers; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Disease Models, Animal; Energy Metabolism; Gastrointestinal Microbiome; Glutathione; Glyceraldehyde; Host Microbial Interactions; Humans; Intestinal Mucosa; Metabolomics; Metagenomics; Mice; Models, Biological; Oxidation-Reduction; Oxidative Stress; Propane; Signal Transduction; Xenograft Model Antitumor Assays
PubMed: 34951957
DOI: 10.1016/j.ccell.2021.12.001 -
Cell Metabolism Jan 2020Iron is a central micronutrient needed by all living organisms. Competition for iron in the intestinal tract is essential for the maintenance of indigenous microbial...
Iron is a central micronutrient needed by all living organisms. Competition for iron in the intestinal tract is essential for the maintenance of indigenous microbial populations and for host health. How symbiotic relationships between hosts and native microbes persist during times of iron limitation is unclear. Here, we demonstrate that indigenous bacteria possess an iron-dependent mechanism that inhibits host iron transport and storage. Using a high-throughput screen of microbial metabolites, we found that gut microbiota produce metabolites that suppress hypoxia-inducible factor 2α (HIF-2α) a master transcription factor of intestinal iron absorption and increase the iron-storage protein ferritin, resulting in decreased intestinal iron absorption by the host. We identified 1,3-diaminopropane (DAP) and reuterin as inhibitors of HIF-2α via inhibition of heterodimerization. DAP and reuterin effectively ameliorated systemic iron overload. This work provides evidence of intestine-microbiota metabolic crosstalk that is essential for systemic iron homeostasis.
Topics: Adolescent; Animals; Anti-Bacterial Agents; Basic Helix-Loop-Helix Transcription Factors; Cell Line; Cell Proliferation; Diamines; Dimerization; Duodenum; Feces; Female; Ferritins; Gastrointestinal Microbiome; Glyceraldehyde; Homeostasis; Humans; Iron; Lactobacillus; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Organoids; Probiotics; Propane; Signal Transduction
PubMed: 31708445
DOI: 10.1016/j.cmet.2019.10.005 -
Microbial Cell Factories Nov 2020The development of sustainable routes to the bio-manufacture of gaseous hydrocarbons will contribute widely to future energy needs. Their realisation would contribute... (Review)
Review
The development of sustainable routes to the bio-manufacture of gaseous hydrocarbons will contribute widely to future energy needs. Their realisation would contribute towards minimising over-reliance on fossil fuels, improving air quality, reducing carbon footprints and enhancing overall energy security. Alkane gases (propane, butane and isobutane) are efficient and clean-burning fuels. They are established globally within the transportation industry and are used for domestic heating and cooking, non-greenhouse gas refrigerants and as aerosol propellants. As no natural biosynthetic routes to short chain alkanes have been discovered, de novo pathways have been engineered. These pathways incorporate one of two enzymes, either aldehyde deformylating oxygenase or fatty acid photodecarboxylase, to catalyse the final step that leads to gas formation. These new pathways are derived from established routes of fatty acid biosynthesis, reverse β-oxidation for butanol production, valine biosynthesis and amino acid degradation. Single-step production of alkane gases in vivo is also possible, where one recombinant biocatalyst can catalyse gas formation from exogenously supplied short-chain fatty acid precursors. This review explores current progress in bio-alkane gas production, and highlights the potential for implementation of scalable and sustainable commercial bioproduction hubs.
Topics: Alkanes; Biofuels; Biosynthetic Pathways; Butanes; Carboxy-Lyases; Fatty Acids; Gases; Genetic Engineering; Industrial Microbiology; Metabolic Engineering; Oxidation-Reduction; Oxygenases; Propane; Synthetic Biology
PubMed: 33187524
DOI: 10.1186/s12934-020-01470-6 -
Environmental Science & Technology Jul 2023Exposure pathways to the carcinogen benzene are well-established from tobacco smoke, oil and gas development, refining, gasoline pumping, and gasoline and diesel...
Exposure pathways to the carcinogen benzene are well-established from tobacco smoke, oil and gas development, refining, gasoline pumping, and gasoline and diesel combustion. Combustion has also been linked to the formation of nitrogen dioxide, carbon monoxide, and formaldehyde indoors from gas stoves. To our knowledge, however, no research has quantified the formation of benzene indoors from gas combustion by stoves. Across 87 homes in California and Colorado, natural gas and propane combustion emitted detectable and repeatable levels of benzene that in some homes raised indoor benzene concentrations above well-established health benchmarks. Mean benzene emissions from gas and propane burners on high and ovens set to 350 °F ranged from 2.8 to 6.5 μg min, 10 to 25 times higher than emissions from electric coil and radiant alternatives; neither induction stoves nor the food being cooked emitted detectable benzene. Benzene produced by gas and propane stoves also migrated throughout homes, in some cases elevating bedroom benzene concentrations above chronic health benchmarks for hours after the stove was turned off. Combustion of gas and propane from stoves may be a substantial benzene exposure pathway and can reduce indoor air quality.
Topics: Air Pollution, Indoor; Benzene; Propane; Gasoline; Household Products; Cooking; Air Pollutants
PubMed: 37319002
DOI: 10.1021/acs.est.2c09289 -
ACS Omega Feb 2022To expand the knowledge on hydrocarbon selective catalytic reduction (SCR) and follow the research steps of methane-SCR and propane-SCR in our previous work, we studied...
To expand the knowledge on hydrocarbon selective catalytic reduction (SCR) and follow the research steps of methane-SCR and propane-SCR in our previous work, we studied the characteristics of propane adsorption on In/BEA zeolite, explored the NO and NO activation process on a propane adsorbed catalyst, and calculated the reaction enthalpy of two reaction pathways. Results showed that O site in the L-model (the [InO]/BEA structure) was the main active site in the adsorption process, and any of the carbon atoms in the propane molecule could react with it, with a lower adsorption energy than methane (-3.20 vs -2.98 eV). Also, NO or NO could not be directly activated on the propane adsorbed catalyst, indicating that the process may be complicated. In addition, propane reduces the NO or NO molecule with two different pathways and the final products were less stable than those of methane (-5.6 vs -20 eV). These results could explain the fact that propane and methane had different reaction temperatures and would further deepen our understanding of the propane-SCR process.
PubMed: 35155942
DOI: 10.1021/acsomega.1c06414 -
IARC Monographs on the Evaluation of... 1999
Review
Topics: Animals; Carcinogenicity Tests; Carcinogens; Humans; Insecticides; Mutagenicity Tests; Mutagens; Neoplasms; Neoplasms, Experimental; Propane
PubMed: 10476458
DOI: No ID Found -
The ISME Journal Jul 2022Natural gas seeps release significant amounts of methane and other gases including ethane and propane contributing to global climate change. In this study, bacterial...
Natural gas seeps release significant amounts of methane and other gases including ethane and propane contributing to global climate change. In this study, bacterial actively consuming short-chain alkanes were identified by cultivation, whole-genome sequencing, and stable-isotope probing (SIP)-metagenomics using C-propane and C-ethane from two different natural gas seeps, Pipe Creek and Andreiasu Everlasting Fire. Nearly 100 metagenome-assembled genomes (MAGs) (completeness 70-99%) were recovered from both sites. Among these, 16 MAGs had genes encoding the soluble di-iron monooxygenase (SDIMO). The MAGs were affiliated to Actinobacteria (two MAGs), Alphaproteobacteria (ten MAGs), and Gammaproteobacteria (four MAGs). Additionally, three gaseous-alkane degraders were isolated in pure culture, all of which could grow on ethane, propane, and butane and possessed SDIMO-related genes. Two Rhodoblastus strains (PC2 and PC3) were from Pipe Creek and a Mycolicibacterium strain (ANDR5) from Andreiasu. Strains PC2 and PC3 encoded putative butane monooxygenases (MOs) and strain ANDR5 contained a propane MO. Mycolicibacterium strain ANDR5 and MAG19a, highly abundant in incubations with C-ethane, share an amino acid identity (AAI) of 99.3%. We show using a combination of enrichment and isolation, and cultivation-independent techniques, that these natural gas seeps contain a diverse community of active bacteria oxidising gaseous-alkanes, which play an important role in biogeochemical cycling of natural gas.
Topics: Alkanes; Bacteria; Butanes; Ethane; Gases; Mixed Function Oxygenases; Natural Gas; Phylogeny; Propane
PubMed: 35319019
DOI: 10.1038/s41396-022-01211-0 -
Nature Genetics Nov 2020Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from...
Epidemiological studies have identified many environmental agents that appear to significantly increase cancer risk in human populations. By analyzing tumor genomes from mice chronically exposed to 1 of 20 known or suspected human carcinogens, we reveal that most agents do not generate distinct mutational signatures or increase mutation burden, with most mutations, including driver mutations, resulting from tissue-specific endogenous processes. We identify signatures resulting from exposure to cobalt and vinylidene chloride and link distinct human signatures (SBS19 and SBS42) with 1,2,3-trichloropropane, a haloalkane and pollutant of drinking water, and find these and other signatures in human tumor genomes. We define the cross-species genomic landscape of tumors induced by an important compendium of agents with relevance to human health.
Topics: Animals; Carcinogenesis; Carcinogens; DNA Mutational Analysis; Environmental Pollutants; Female; Genome; Humans; Male; Mice; Mutation; Mutation Rate; Propane; Species Specificity
PubMed: 32989322
DOI: 10.1038/s41588-020-0692-4 -
Nature Communications Oct 2022Anaerobic microorganisms are thought to play a critical role in regulating the flux of short-chain gaseous alkanes (SCGAs; including ethane, propane and butane) from...
Anaerobic microorganisms are thought to play a critical role in regulating the flux of short-chain gaseous alkanes (SCGAs; including ethane, propane and butane) from terrestrial and aquatic ecosystems to the atmosphere. Sulfate has been confirmed to act as electron acceptor supporting microbial anaerobic oxidation of SCGAs, yet several other energetically more favourable acceptors co-exist with these gases in anaerobic environments. Here, we show that a bioreactor seeded with biomass from a wastewater treatment facility can perform anaerobic propane oxidation coupled to nitrate reduction to dinitrogen gas and ammonium. The bioreactor was operated for more than 1000 days, and we used C- and N-labelling experiments, metagenomic, metatranscriptomic, metaproteomic and metabolite analyses to characterize the microbial community and the metabolic processes. The data collectively suggest that a species representing a novel order within the bacterial class Symbiobacteriia is responsible for the observed nitrate-dependent propane oxidation. The closed genome of this organism, which we designate as 'Candidatus Alkanivorans nitratireducens', encodes pathways for oxidation of propane to CO via fumarate addition, and for nitrate reduction, with all the key genes expressed during nitrate-dependent propane oxidation. Our results suggest that nitrate is a relevant electron sink for SCGA oxidation in anaerobic environments, constituting a new microbially-mediated link between the carbon and nitrogen cycles.
Topics: Alkanes; Ammonium Compounds; Anaerobiosis; Butanes; Carbon; Carbon Dioxide; Ecosystem; Ethane; Fumarates; Methane; Nitrates; Oxidation-Reduction; Propane; Sulfates
PubMed: 36253480
DOI: 10.1038/s41467-022-33872-y -
Water Research May 2023Nitrate contamination has been commonly detected in water environments and poses serious hazards to human health. Previously methane was proposed as a promising electron...
Nitrate contamination has been commonly detected in water environments and poses serious hazards to human health. Previously methane was proposed as a promising electron donor to remove nitrate from contaminated water. Compared with pure methane, natural gas, which not only contains methane but also other short chain gaseous alkanes (SCGAs), is less expensive and more widely available, representing a more attractive electron source for removing oxidized contaminants. However, it remains unknown if these SCGAs can be utilized as electron donors for nitrate reduction. Here, two lab-scale membrane biofilm reactors (MBfRs) separately supplied with propane and butane were operated under oxygen-limiting conditions to test its feasibility of microbial nitrate reduction. Long-term performance suggested nitrate could be continuously removed at a rate of ∼40-50 mg N/L/d using propane/butane as electron donors. In the absence of propane/butane, nitrate removal rates significantly decreased both in the long-term operation (∼2-10 and ∼4-9 mg N/L/d for propane- and butane-based MBfRs, respectively) and batch tests, indicating nitrate bio-reduction was driven by propane/butane. The consumption rates of nitrate and propane/butane dramatically decreased under anaerobic conditions, but recovered after resupplying limited oxygen, suggesting oxygen was an essential triggering factor for propane/butane-based nitrate reduction. High-throughput sequencing targeting 16S rRNA, bmoX and narG genes indicated Mycobacterium/Rhodococcus/Thauera were the potential microorganisms oxidizing propane/butane, while various denitrifiers (e.g. Dechloromonas, Denitratisoma, Zoogloea, Acidovorax, Variovorax, Pseudogulbenkiania and Rhodanobacter) might perform nitrate reduction in the biofilms. Our findings provide evidence to link SCGA oxidation with nitrate reduction under oxygen-limiting conditions and may ultimately facilitate the design of cost-effective techniques for ex-situ groundwater remediation using natural gas.
Topics: Humans; Propane; Nitrates; Natural Gas; RNA, Ribosomal, 16S; Alkanes; Methane; Butanes; Oxidation-Reduction; Biofilms; Oxygen; Water; Bioreactors
PubMed: 36947926
DOI: 10.1016/j.watres.2023.119887