Jianbo Zhang

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Zhang

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Jianbo

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0000-0003-3526-4586

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Publications 1 - 7 of 7

Impact of manipulation of glycerol/diol dehydratase activity on intestinal microbiota ecology and metabolism
Ramirez Garcia, Alejandro; Zhang, Jianbo; Greppi, Anna; et al. (2021)
Environmental Microbiology
Glycerol/diol dehydratases (GDH) are enzymes that catalyse the production of propionate from 1,2‐propanediol, and acrolein from glycerol. Acrolein reacts with dietary carcinogenic heterocyclic amines (HCA), reducing HCA mutagenicity, but is itself also an antimicrobial agent and toxicant. Gut microbial GDH activity has been suggested as an endogenous acrolein source; however, there is limited information on the potential of the intestinal microbiota to have GDH activity, and what impact it can have on the intestinal ecosystem and host health. We hypothesized that GDH activity of gut microbiota is determined by the abundance and distribution of GDH‐active taxa and can be enhanced by supplementation of the GDH active Anaerobutyricum hallii, and tested this hypothesis combining quantitative profiling of gdh, model batch fermentations, microbiota manipulation, and kinetic modelling of acrolein formation. Our results suggest that GDH activity is a common trait of intestinal microbiota shared by a few taxa, which was dependent on overall gdh abundance. Anaerobutyricum hallii was identified as a key taxon in GDH metabolism, and its supplementation increased the rate of GDH activity and acrolein release, which enhanced the transformation of HCA and reduced fermentation activity. The findings of this first systematic study on acrolein release by intestinal microbiota indicate that dietary and microbial modulation might impact GDH activity, which may influence host health. © 2021 Society for Applied Microbiology and John Wiley & Sons Ltd.
A WRF-CMAQ modeling of atmospheric peroxyacetyl nitrate and source apportionment in Central China
Wang, Yifei; Sun, Mei; Qiao, Xueqi; et al. (2023)
Science of The Total Environment
Atmospheric peroxyacetyl nitrate (PAN), as an essential constituent in the photochemical smog, is formed from photochemical reactions between volatile organic compounds (VOCs) and NOx. However, limited regional studies on distribution, formation and sources of PAN restrict the further understanding of the atmospheric behavior and environmental significance of PAN. In this study, the variation characteristics of PAN and the influencing factors to PAN concentrations were investigated using the WRF-CMAQ model simulation in the central China during July 2019. The results showed that the monthly mean concentration of PAN in the near-surface layer was 0.4 ppbv and increased with the height rising, accompanied by strong intra-day variation. The process analysis suggested that the removal was mainly controlled by dry deposition (57 %), followed by the gas-phase chemistry (43 %) which was mainly attributed to the thermal decomposition. Based on the sensitivity simulation, PAN concentrations decreased effectively in most of the simulated regions when precursors of VOCs and NOx emissions were reduced, and PAN concentrations were more sensitive to VOCs emissions than NOx emissions. The reduction of NOx and VOCs could lead to enhanced atmospheric oxidation in east-central region, which in turn hindered the decrease of PAN concentrations. During the simulation period, we found that emissions from industry and transportation sectors had the greatest impact on PAN concentrations in the central China, with contributions of 39 %–49 % and 33 %–41 %, respectively.
Gut microbial transformation of the dietary mutagen MeIQx may reduce exposure levels without altering intestinal transport
Zhang, Jianbo; Empl, Michael T.; Schneider, Mirjam; et al. (2019)
Toxicology in Vitro
Impact of Gut Microbiota on the Metabolism of Carcinogenic Dietary Heterocyclic Amines
Zhang, Jianbo (2018)
Human are constantly exposed to potentially toxic chemicals from the environment, diet, and therapeutic interventions. However, the gut harbors a diverse community of microorganisms, which may alter the exposure and toxicity of these chemicals. Heterocyclic amines (HCAs) are mutagens presented in meat cooked at high temperature, and they are strongly associated with the increased risk of colorectal cancer. Bacterial transformation of HCAs may alter their structures and thus their toxicity, but little is known regarding the influence of gut microbiota on the risk associated with these chemicals due to the existing knowledge gap regarding the microbiota-chemical interactions. The work described in this thesis concerns the chemical and biochemical mechanisms of commensal gut bacterial transformation of HCAs and their liver metabolites, as well as toxicological and physiological relevance of the microbial transformations. The knowledge obtained provides mechanistic insights on how gut microbiota alter chemical toxicity and supports gut microbiota as a factor in the risk assessment of toxic chemicals. Chapter 1 introduces the background information concerning the microbial metabolism of glycerol in the human gut and its relevance to HCA transformation. In addition, an overview of the potential targets of gut bacteria-derived acrolein is given. In Chapter 2, we aimed to address the generality of bacterial conjugation of HCAs with acrolein. MeIQx is an imidazoquinoxaline mutagen ten times more mutagenic than PhIP toward bacterial DNA in vitro assays. E. hallii, Lactobacillus reuteri, and Lactobacillus rossiae were found to convert MeIQx to a new microbial metabolite characterized on the basis of HRMS and NMR as 9-hydroxyl-2,7-dimethyl-7,9,10,11-tetrahydropyrimido-[2′,1′:2,3]imidazo[4,5-f]quinoxaline (MeIQx-M1). Acrolein derived from the decomposition of 3-HPA, which is a product of glycerol reduction mediated by GDH activity, was identified as the active compound responsible for the formation of MeIQx-M1. MeIQx-M1 appears to have slightly reduced cytotoxic potency toward human colon epithelial cells, and diminished mutagenic potential toward bacteria after metabolic activation. In Chapter 3, the physiological and toxicological relevance of the microbial transformation of MeIQx to MeIQx-M1 was characterized. To address whether the microbial transformation influences the intestinal transport of MeIQx, the intestinal uptake of MeIQx and its metabolite MeIQx-M1 was quantified with ex vivo rat intestinal segments, however, only negligible amounts of both MeIQx and MeIQx-M1 were transported. In addition, neither MeIQx nor MeIQx-M1 were cytotoxic towards liver HepaRG cells at dietary levels or higher concentrations. Physiologically based pharmacokinetic modeling suggests that increased microbial transformation of MeIQx can reduce plasma levels of MeIQx, potentially contributing to reduced systemic exposure of MeIQx in human. In Chapter 4, the impact of commensal gut microbes on the transformation of HCA liver metabolites, especially glucuronide conjugates was investigated. The aim was to gain knowledge regarding how gut microbes coordinate to transform HCA-glucuronides to release HCAs and further convert them to HCA-M1s. The beta-glucuronidase (GUSB) produced by species belong to Eubacterium and Faecalibacterium catalyzed the re-activation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine N2-β-D-glucuronide (PhIP-G), a liver metabolite of PhIP, to form PhIP. GDH of Flavonifractor plautii, Blautia obeum, E. hallii, and L. reuteri contributed the detoxification of PhIP to form PhIP-M1. Co-culture of GUSB+ strain and GDH+ strain led to the conversion of PhIP-G to PhIP and PhIP-M1. These results for the first time demonstrate the gut microbial transformation of PhIP-G to PhIP-M1, providing a mechanistic model for reducing PhIP exposure from enterohepatic circulation by linking the modification of a carcinogen with the metabolic activity of predominant gut microbes. In Chapter 5, the chemical scope of the reaction of acrolein with HCAs was expanded. The aim of this study was to gain knowledge on the reactivity of heterocyclic guanines (HCGs) with α,β-unsaturated aldehydes (UAs). Results suggest that HCGs react with acrolein to form products bearing a hydroxyltetrahydropyrimidine ring. Substitution on both α and β positions of acrolein dramatically reduced reactivity and acrolein had the highest reactivity among the tested UAs. Moreover, two drugs bearing a guanidine moiety can readily react with acrolein with 491-721 times faster than that of DNA base with acrolein. These findings suggest the guanidine conjugation with acrolein is a general reaction of HCGs mediated by bacterial acrolein and HCGs are scavengers of acrolein. Chapter 6 summarizes the findings and gives an outlook. A critical discussion of achievements and limitations is provided and ongoing future directions are presented.
Initial butyrate producers during infant gut microbiota development are endospore formers
Appert, Olivia; Garcia, Alejandro R.; Frei, Remo; et al. (2020)
Environmental Microbiology
The acquisition of the infant gut microbiota is key to establishing a host‐microbiota symbiosis. Microbially produced metabolites tightly interact with the immune system, and the fermentation‐derived short‐chain fatty acid butyrate is considered an important mediator linked to chronic diseases later in life. The intestinal butyrate‐forming bacterial population is taxonomically and functionally diverse and includes endospore formers with high transmission potential. Succession, and contribution of butyrate‐producing taxa during infant gut microbiota development have been little investigated. We determined the abundance of major butyrate‐forming groups and fermentation metabolites in faeces, isolated, cultivated and characterized the heat‐resistant cell population, which included endospores, and compared butyrate formation efficiency of representative taxa in batch cultures. The endospore community contributed about 0.001% to total cells, and was mainly composed of the pioneer butyrate‐producing Clostridium sensu stricto. We observed an increase in abundance of Faecalibacterium prausnitzii, butyrate‐producing Lachnospiraceae and faecal butyrate levels with age that is likely explained by higher butyrate production capacity of contributing taxa compared with Clostridium sensu stricto. Our data suggest that a successional arrangement and an overall increase in abundance of butyrate forming populations occur during the first year of life, which is associated with an increase of intestinal butyrate formation capacity.
Heterogeneous Reaction of Peroxyacetyl Nitrate on Real-World PM₂.₅ Aerosols: Kinetics, Influencing Factors, and Atmospheric Implications
Sun, Mei; Zhou, Ying; Wang, Yifei; et al. (2022)
Environmental Science & Technology
The formation and decomposition of peroxyacetyl nitrate (PAN), an important atmospheric nitrogen oxide reservoir, can impact the level and cycling of free radicals and nitrogen compounds in the atmosphere. PAN sinks are poorly understood, highlighting the importance of elucidating the heterogeneous reaction of PAN on aerosol surfaces. Here, we report for the first time the uptake behavior, kinetics, and potential mechanism of PAN uptake on real-world aerosol PM2.5 using a flow tube system. The uptake coefficients (γ) of PAN increased non-linearly from (1.5 ± 0.7) × 10–5 at 0% relative humidity (RH) to (9.3 ± 2.0) × 10–5 at 80% RH. The γ decrease with increasing initial PAN concentration is consistent with the Langmuir–Hinshelwood mechanism. Organic components of aerosols may promote heterogeneous loss of PAN through redox reactions. Higher γ occurs with higher water content, lower pH, and lower ionic strength in the aqueous phase of aerosols. The present study suggests that heterogeneous reaction of PAN on ambient aerosols plays a non-negligible role in the atmospheric PAN budget and provides new insights into the role of PAN in promoting atmospheric oxidation capacity during hazy periods with cold and wet weather conditions.
Gut microbial beta-glucuronidase and glycerol/diol dehydratase activity contribute to dietary heterocyclic amine biotransformation
Zhang, Jianbo; Lacroix, Christophe; Wortmann, Esther; et al. (2019)
BMC Microbiology
Background Consuming red and processed meat has been associated with an increased risk of colorectal cancer (CRC), which is partly attributed to exposure to carcinogens such as heterocyclic amines (HCA) formed during cooking and preservation processes. The interaction of gut microbes and HCA can result in altered bioactivities and it has been shown previously that human gut microbiota can transform mutagenic HCA to a glycerol conjugate with reduced mutagenic potential. However, the major form of HCA in the colon are glucuronides (HCA-G) and it is not known whether these metabolites, via stepwise microbial hydrolysis and acrolein conjugation, are viable precursors for glycerol conjugated metabolites. We hypothesized that such a process could be concurrently catalyzed by bacterial beta-glucuronidase (B-GUS) and glycerol/diol dehydratase (GDH) activity. We therefore investigated how the HCA-G PhIP-N2-β-D-glucuronide (PhIP-G), a representative liver metabolite of PhIP (2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), which is the most abundant carcinogenic HCA in well-cooked meat, is transformed by enzymatic activity of human gut microbial representatives of the phyla Firmicutes, Bacteroidetes, and Proteobacteria. Results We employed a combination of growth and enzymatic assays, and a bioanalysis approach combined with metagenomics. B-GUS of Faecalibacterium prausnitzii converted PhIP-G to PhIP and GDH of Flavonifractor plautii, Blautia obeum, Eubacterium hallii, and Lactobacillus reuteri converted PhIP to PhIP-M1 in the presence of glycerol. In addition, B-GUS- and GDH-positive bacteria cooperatively converted PhIP-G to PhIP-M1. A screen of genes encoding B-GUS and GDH was performed for fecal microbiome data from healthy individuals (n = 103) and from CRC patients (n = 53), which revealed a decrease in abundance of taxa with confirmed GDH and HCA transformation activity in CRC patients. Conclusions This study for the first time demonstrates that gut microbes mediate the stepwise transformation of PhIP-G to PhIP-M1 via the intermediate production of PhIP. Findings from this study suggest that targeted manipulation with gut microbes bearing specific functions, or dietary glycerol supplementation might modify gut microbial activity to reduce HCA-induced CRC risk.

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