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Science Advances Jan 2023Atopic dermatitis (AD) is a chronic inflammatory skin condition increasing in industrial nations at a pace that suggests environmental drivers. We hypothesize that the...
Atopic dermatitis (AD) is a chronic inflammatory skin condition increasing in industrial nations at a pace that suggests environmental drivers. We hypothesize that the dysbiosis associated with AD may signal microbial adaptations to modern pollutants. Having previously modeled the benefits of health-associated , we now show that fixes nitrogen in the production of protective glycerolipids and their ceramide by-products. Screening EPA databases against the clinical visit rates identified diisocyanates as the strongest predictor of AD. Diisocyanates disrupted the production of beneficial lipids and therapeutic modeling for isolates of as well as commensal . Last, while topical failed to meet commercial end points in a placebo-controlled trial, the subgroup who completed the full protocol demonstrated sustained, clinically modest, but statistically significant clinical improvements that differed by study site diisocyanate levels. Therefore, diisocyanates show temporospatial and epidemiological association with AD while also inducing eczematous dysbiosis.
Topics: Humans; Dermatitis, Atopic; Dysbiosis; Isocyanates; Prevalence; Bacteria; Skin
PubMed: 36608129
DOI: 10.1126/sciadv.ade8898 -
Frontiers in Immunology 2022The cutaneous microbiome is increasingly recognized as a contributor to skin diseases like atopic dermatitis (AD) and psoriasis. Although traditionally AD and psoriasis...
The cutaneous microbiome is increasingly recognized as a contributor to skin diseases like atopic dermatitis (AD) and psoriasis. Although traditionally AD and psoriasis have been viewed as having opposing immunologic findings, recent evidence suggests an overlap in ceramide-family lipid production in the protection against symptoms. We recently identified that specific environmental pollutants may drive dysbiosis through direct suppression of ceramide-family lipids produced by health-associated skin bacteria in atopic dermatitis (AD). We further demonstrated that one such bacteria, , generated significant clinical improvement in AD lasting beyond active treatment lipid-mediated modulation of tumor necrosis factor (TNF) signaling. To assess the potential preclinical benefit of in psoriasis we assessed for direct effects on surface TNF signaling in cell cultures and identified direct effects on the TNF axis. We also identified preclinical efficacy of treatment in the imiquimod mouse model of psoriasis. Finally, we expanded our previous environmental assessment for psoriasis to include more traditional markers of air quality and found a strong association between disease rates and ambient carbon monoxide (CO), nitrogen dioxide (NO), and particulate matter (PM). At the current stage this work is speculative but does support consideration of further preclinical models and/or clinical assessments to evaluate any potential for therapeutic benefit through microbial manipulation and/or environmental mitigation.
Topics: Animals; Mice; Dermatitis, Atopic; Environmental Pollutants; Psoriasis; Ceramides; Lipids
PubMed: 36605199
DOI: 10.3389/fimmu.2022.1094376 -
Current Research in Translational... 2023Fetal growth restriction (FGR) is a complex obstetric complication with various causes and of great harm. However, the specific pathogenesis of FGR is unclear, which...
BACKGROUND
Fetal growth restriction (FGR) is a complex obstetric complication with various causes and of great harm. However, the specific pathogenesis of FGR is unclear, which limits its effective treatment. Gut microbiota dysbiosis was found to be important in pathogenesis of various diseases. However, its role in FGR development remains unclear and needs to be clarified.
METHODS
In our case-control study, we recruited eight FGR and eight control female participants and collected their fecal samples in third trimester before delivery. We performed metagenomic sequencing and bioinformatic analysis to compare the gut microbiota composition and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the two groups.
RESULTS
Our results showed that totally 20 gut microbes were significantly different between two groups (p<0•05), and the correlation analysis found that g__Roseomonas and g__unclassified_f__Propionibacteriaceae were significantly positive correlated with both maternal body mass index (BMI) before delivery, placental weight, and neonatal birth weight (BW) percentile (all p<0•05), while g__Marinisporobacter and g__Sphingomonas were significantly negative correlated with both neonatal BMI and neonatal BW percentile (all p<0•05). Through KEGG pathway analysis, we found that the abundance of the Nitrogen metabolism pathway decreased significantly (p<0•05) whereas the abundance of the Amoebiasis pathway increased significantly in the FGR group (p<0•05).
CONCLUSION
In this study, we demonstrated that the occurrence of FGR is associated with the change of gut microbiota of pregnant women.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Fetal Growth Retardation; Placenta; Case-Control Studies; Microbiota; Gastrointestinal Microbiome
PubMed: 36434943
DOI: 10.1016/j.retram.2022.103354 -
Frontiers in Microbiology 2022Manure treatment with black soldier fly larvae (BSFL) and BSFL frass application in crop land is a sustainable strategy; however, whether residual antibiotic resistance...
Manure treatment with black soldier fly larvae (BSFL) and BSFL frass application in crop land is a sustainable strategy; however, whether residual antibiotic resistance genes (ARGs) and their transmission risk are related to the manure BSFL treatment process is still unknown. In this paper, the effect of BSFL addition density on residual tetracycline resistance genes (TRGs) and transmission from frass to pakchoi was determined. The results showed that BSFL frass can provide sufficient nutrients for growth, improve the economic value of pakchoi, and reduce the risk of transmission of TRGs in chicken manure regardless of BSFL density. The potential hosts of the TRGs we detected were found in BSFL frass ( and ), rhizosphere soil ( and ), and pakchoi endophytes (). The present study concluded that BSFL frass produced by adding 100 BSFL per 100 g of chicken manure has the advantages of high value and low risk. These findings will provide important strategic guidance for animal manure disposal and theoretical support for preventing the transmission of TRGs in BSFL applications.
PubMed: 36386720
DOI: 10.3389/fmicb.2022.1014910 -
Metabolic Engineering Nov 2022Formate is a promising, water-soluble C1 feedstock for biotechnology that can be efficiently produced from CO-but formatotrophy has been engineered in only a few...
Formate is a promising, water-soluble C1 feedstock for biotechnology that can be efficiently produced from CO-but formatotrophy has been engineered in only a few industrially-relevant microbial hosts. We addressed the challenge of expanding the feedstock range of bacterial hosts by adopting Pseudomonas putida as a robust platform for synthetic formate assimilation. Here, the metabolism of a genome-reduced variant of P. putida was radically rewired to establish synthetic auxotrophies that could be functionally complemented by expressing components of the reductive glycine (rGly) pathway. We adopted a modular engineering approach, dividing C1 assimilation in segments composed of both heterologous activities (sourced from Methylobacterium extorquens) and native biochemical reactions. Modular expression of rGly pathway elements enabled growth on formate as carbon source and acetate (predominantly for energy supply), and adaptive laboratory evolution of two lineages of engineered P. putida formatotrophs lead to doubling times of ca. 15 h. We likewise identified emergent metabolic features for assimilation of C1 units in these evolved P. putida populations. Taken together, our results consolidate the landscape of useful microbial platforms that can be implemented for C1-based biotechnological production towards a formate bioeconomy.
Topics: Pseudomonas putida; Metabolic Engineering; Formates; Methylobacterium extorquens; Glycine
PubMed: 36328297
DOI: 10.1016/j.ymben.2022.10.008 -
JID Innovations : Skin Science From... Sep 2022The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease....
The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease. Nasal swabs from 45 patients with CTCL (40 with mycosis fungoides, 5 with Sézary syndrome) and 20 healthy controls from the same geographical region (Chicago Metropolitan Area, Chicago, IL) were analyzed using sequencing of 16S ribosomal RNA and gene amplicons. Nasal α-diversity did not differ between mycosis fungoides/Sézary syndrome and healthy controls (Shannon index, genus level, = 0.201), but distinct microbial communities were identified at the class (R = 0.104, = 0.023) and order (R = 0.0904, = 0.038) levels. Increased relative abundance of the genera , , , , and unclassified Clostridiales was associated with increased skin disease burden ( < 0.005, q < 0.05). Performed to accurately resolve nasal at the species level, gene amplicon sequencing revealed no significant differences between mycosis fungoides/Sézary syndrome and healthy controls. Although has been shown to worsen CTCL through its toxins, no increase in the relative abundance of this taxon was observed in nasal samples. Despite the lack of differences in the CTCL nasal microbiome was characterized by shifts in numerous other bacterial taxa. These data add to our understanding of the greater CTCL microbiome and provide context for comprehending nasal-skin and host‒tumor‒microbial relationships.
PubMed: 36161104
DOI: 10.1016/j.xjidi.2022.100132 -
Bioactive Materials Mar 2023Many skin diseases, such as atopic dermatitis (AD), are featured with the dysbiosis of skin microbiota. The clinically recommended options for AD treatments suffer from...
Many skin diseases, such as atopic dermatitis (AD), are featured with the dysbiosis of skin microbiota. The clinically recommended options for AD treatments suffer from poor outcomes and high side-effects, leading to severe quality-of-life impairment. To deal with this long-term challenge, we develop a living bacterial formulation (Hy@Rm) that integrates skin symbiotic bacteria of with poly(vinyl pyrrolidone), poly(vinyl alcohol) and sodium alginate into a skin dressing by virtue of the Ca-mediated cross-linking and the freezing-thawing (F-T) cycle method. Hy@Rm dressing creates a favorable condition to not only serve as extrinsic culture harbors but also as nutrient suppliers to support . survival in the harsh microenvironment of AD sites to defeat which predominantly colonizes AD skins as an indigenous pathogen, mainly through the secretion of sphingolipids metabolites by . like a therapeutics bio-factory. Meanwhile, this elaborately designed skin dressing could accelerate wound healing, normalize aberrant skin characters, recover skin barrier functions, alleviate AD-associated immune/inflammation responses, functioning like a combinational therapy. This study offers a promising means for the topical bacteria transplant to realize effective microbe biotherapy toward the skin diseases feature with microbe milieu disorders, including but not limited to AD disease.
PubMed: 36157249
DOI: 10.1016/j.bioactmat.2022.08.019 -
International Journal of Molecular... Sep 2022(Ca)-dependent pyrroloquinolinequinone (PQQ)-dependent methanol dehydrogenase (MDH) (EC: 1.1.2.7) is one of the key enzymes of primary C1-compound metabolism in...
(Ca)-dependent pyrroloquinolinequinone (PQQ)-dependent methanol dehydrogenase (MDH) (EC: 1.1.2.7) is one of the key enzymes of primary C1-compound metabolism in methylotrophy. PQQ-MDH is a promising catalyst for electrochemical biosensors and biofuel cells. However, the large-scale use of PQQ-MDH in bioelectrocatalysis is not possible due to the low yield of the native enzyme. Homologously overexpressed MDH was obtained from methylotrophic bacterium AM1 by cloning the gene of only one subunit, . The His-tagged enzyme was easily purified by immobilized metal ion affinity chromatography (36% yield). A multimeric form (α6β6) of recombinant PQQ-MDH possessing enzymatic activity (0.54 U/mg) and high stability was demonstrated for the first time. pH-optimum of the purified protein was about 9-10; the enzyme was activated by ammonium ions. It had the highest affinity toward methanol (K = 0.36 mM). The recombinant MDH was used for the fabrication of an amperometric biosensor. Its linear range for methanol concentrations was 0.002-0.1 mM, the detection limit was 0.7 µM. The properties of the invented biosensor are competitive to the analogs, meaning that this enzyme is a promising catalyst for industrial methanol biosensors. The developed simplified technology for PQQ-MDH production opens up new opportunities for the development of bioelectrocatalytic systems.
Topics: Alcohol Oxidoreductases; Ammonium Compounds; Ions; Methanol; Methylobacterium extorquens
PubMed: 36142248
DOI: 10.3390/ijms231810337 -
Frontiers in Microbiology 2022Understanding the distribution patterns and shaping factors of bacterial pathogens in aquatic ecosystems, especially in natural waters, are critical to the control of...
Understanding the distribution patterns and shaping factors of bacterial pathogens in aquatic ecosystems, especially in natural waters, are critical to the control of pathogen transmission. In this study, using gene amplicon sequencing, we explored the composition and biogeographic dynamics of potential bacterial pathogens in the middle and lower reaches of the Yangtze River, as well as its two vast adjoining lakes (Dongting Lake and Poyang Lake). The pathogen community belonged to 12 potential pathogenic groups, with "intracellular parasites," "animal parasites or symbionts" and "human pathogens all" occupying 97.5% in total. The potential pathogen community covered seven phyla with Proteobacteria (69.8%) and Bacteroidetes (13.5%) the most predominant. In addition, 53 genera were identified with (15.2%) and (14.2%) the most dominant. The average relative abundance, alpha diversity and microbial composition of the potential bacterial pathogens exhibited significant biogeographical variations among the different sections. An in-depth analysis reflected that environmental variables significantly structured the potential bacterial pathogens, including water physiochemical properties (i.e., chlorophyll-, total nitrogen and transparency), heavy metals (i.e., As and Ni), climate (i.e., air temperature) and land use type (i.e., waters). Compared to the overall bacterial community which was composed of both pathogenic and non-pathogenic bacteria, the pathogen community exhibited distinct microbial diversity patterns and shaping factors. This signifies the importance of different variables for shaping the pathogen community. This study represents one attempt to explore pathogen diversity patterns and their underlying drivers in the Yangtze River, which provides a foundation for the management of pathogenic bacteria.
PubMed: 36118197
DOI: 10.3389/fmicb.2022.972243 -
Applied Microbiology and Biotechnology Oct 2022The methylotrophic bacterium Methylorubrum extorquens AM1 has the potential to become a platform organism for methanol-driven biotechnology. Its ethylmalonyl-CoA pathway...
The methylotrophic bacterium Methylorubrum extorquens AM1 has the potential to become a platform organism for methanol-driven biotechnology. Its ethylmalonyl-CoA pathway (EMCP) is essential during growth on C1 compounds and harbors several CoA-activated dicarboxylic acids. Those acids could serve as precursor molecules for various polymers. In the past, two dicarboxylic acid products, namely mesaconic acid and 2-methylsuccinic acid, were successfully produced with heterologous thioesterase YciA from Escherichia coli, but the yield was reduced by product reuptake. In our study, we conducted extensive research on the uptake mechanism of those dicarboxylic acid products. By using 2,2-difluorosuccinic acid as a selection agent, we isolated a dicarboxylic acid import mutant. Analysis of the genome of this strain revealed a deletion in gene dctA2, which probably encodes an acid transporter. By testing additional single, double, and triple deletions, we were able to rule out the involvement of the two other DctA transporter homologs and the ketoglutarate transporter KgtP. Uptake of 2-methylsuccinic acid was significantly reduced in dctA2 mutants, while the uptake of mesaconic acid was completely prevented. Moreover, we demonstrated M. extorquens-based synthesis of citramalic acid and a further 1.4-fold increase in product yield using a transport-deficient strain. This work represents an important step towards the development of robust M. extorquens AM1 production strains for dicarboxylic acids. KEY POINTS: • 2,2-Difluorosuccinic acid is used to select for dicarboxylic acid uptake mutations. • Deletion of dctA2 leads to reduction of dicarboxylic acid uptake. • Transporter-deficient strains show improved production of citramalic acid.
Topics: Dicarboxylic Acids; Escherichia coli; Fumarates; Malates; Maleates; Methanol; Methylobacterium extorquens; Polymers; Succinates
PubMed: 36104545
DOI: 10.1007/s00253-022-12161-0