scholarly journals Optogenetic operated probiotics to regulate host metabolism by mimicking enteroendocrine

2021 ◽  
Author(s):  
Xinyu Zhang ◽  
Ning Ma ◽  
Wei Ling ◽  
Gaoju Pang ◽  
Tao Sun ◽  
...  
Keyword(s):  
Flexible Electronics ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Excitation Wavelength ◽  
Optical Signals ◽  
Glucagon Like Peptide 1 ◽  
Enteroendocrine System ◽  
Rats And Mice ◽  
Host Metabolism

The enteroendocrine system plays an important role in metabolism. The gut microbiome regulates enteroendocrine in an extensive way, arousing attention in biomedicine. However, conventional strategies of enteroendocrine regulation via gut microbiome are usually non-specific or imprecise. Here, an optogenetic operated probiotics system was developed combining synthetic biology and flexible electronics to achieve in situ controllable secretion to mimic enteroendocrine. Firstly, optogenetic engineered Lactococcus lactis (L. lactis) were administrated in the intestinal tract. A wearable optogenetic device was designed to control optical signals remotely. Then, L. lactis could secrete enteroendocrine hormone according to optical signals. As an example, optogenetic L. lactis could secrete glucagon-like peptide-1(GLP-1) under the control of the wearable optogenetic device. To improve the half-life of GLP-1 in vivo, the Fc domain from immunoglobulin was fused. Treated with this strategy, blood glucose, weight and other features were relatively well controlled in rats and mice models. Furthermore, up-conversion microcapsules were introduced to increase the excitation wavelength of the optogenetic system for better penetrability. This strategy has biomedical potential in metabolic diseases therapy by mimicking enteroendocrine.

scholarly journals A role for IRF3-dependent RXRα repression in hepatotoxicity associated with viral infections

2006 ◽  
Vol 203 (12) ◽  
pp. 2589-2602 ◽  
Author(s):  
Edward K. Chow ◽  
Antonio Castrillo ◽  
Arash Shahangian ◽  
Liming Pei ◽  
Ryan M. O'Connell ◽  
...  
Keyword(s):  
Viral Infection ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Viral Infections ◽  
Type I ◽  
Reye's Syndrome ◽  
Downstream Target ◽  
Antiviral Responses ◽  
Host Metabolism

Viral infections and antiviral responses have been linked to several metabolic diseases, including Reye's syndrome, which is aspirin-induced hepatotoxicity in the context of a viral infection. We identify an interferon regulatory factor 3 (IRF3)–dependent but type I interferon–independent pathway that strongly inhibits the expression of retinoid X receptor α (RXRα) and suppresses the induction of its downstream target genes, including those involved in hepatic detoxification. Activation of IRF3 by viral infection in vivo greatly enhances bile acid– and aspirin-induced hepatotoxicity. Our results provide a critical link between the innate immune response and host metabolism, identifying IRF3-mediated down-regulation of RXRα as a molecular mechanism for pathogen-associated metabolic diseases.

scholarly journals Recombinant Expression and Stapling of a Novel Long-Acting GLP-1R Peptide Agonist

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2508
Author(s):  
Sam Lear ◽  
Hyosuk Seo ◽  
Candy Lee ◽  
Lei Lei ◽  
Zaid Amso ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Recombinant Expression ◽  
Scale Up ◽  
Single Step ◽  
Binding Motif ◽  
Linear Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting ◽  
Diabetes And Obesity

Owing to their pleiotropic metabolic benefits, glucagon-like peptide-1 receptor (GLP-1R) agonists have been successfully utilized for treating metabolic diseases, such as type 2 diabetes and obesity. As part of our efforts in developing long-acting peptide therapeutics, we have previously reported a peptide engineering strategy that combines peptide side chain stapling with covalent integration of a serum protein-binding motif in a single step. Herein, we have used this strategy to develop a second generation extendin-4 analog rigidified with a symmetrical staple, which exhibits an excellent in vivo efficacy in an animal model of diabetes and obesity. To simplify the scale-up manufacturing of the lead GLP-1R agonist, a semisynthesis protocol was successfully developed, which involves recombinant expression of the linear peptide followed by attachment of a polyethylene glycol (PEG)-fatty acid staple in a subsequent chemical reaction step.

Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

2019 ◽  
pp. 1-13 ◽  
Author(s):  
Sunmin Park ◽  
Sunna Kang ◽  
Da Sol Kim
Keyword(s):  
Insulin Resistance ◽  
Gut Microbiota ◽  
Insulin Signaling ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Memory Function ◽  
Amyloid Β ◽  
Impaired Memory ◽  
Ca1 Region ◽  
Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

scholarly journals Impacts of PBDE-47 exposure before, during and after pregnancy on the maternal gut microbiome and its association with host metabolism

2021 ◽  
Vol 222 ◽  
pp. 112530
Author(s):  
Hui Gao ◽  
Xueyan Wan ◽  
Boya Xiao ◽  
Kaichao Yang ◽  
Yafei Wang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Host Metabolism

scholarly journals Sulpiride Serves, a Substrate for the Gut Microbiome

Dose-Response ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 155932582098794
Author(s):  
Imran Mukhtar ◽  
Haseeb Anwar ◽  
Osman Asghar Mirza ◽  
Qasim Ali ◽  
Muhammad Umar Ijaz ◽  
...  
Keyword(s):  
Oral Administration ◽  
Gut Microbiome ◽  
Drug Target ◽  
Membrane Transporters ◽  
Intestinal Microbiome ◽  
Albino Rats ◽  
Body Organ ◽  
Total Absorbance ◽  
Research World

In the contemporary research world, the intestinal microbiome is now envisioned as a new body organ. Recently, the gut microbiome represents a new drug target in the gut, since various orthologues of intestinal drug transporters are also found present in the microbiome that lines the small intestine of the host. Owing to this, absorbance of sulpiride by the gut microbiome in an in vivo albino rats model was assessed after the oral administration with a single dose of 20mg/kg b.w. The rats were subsequently sacrificed at 2, 3, 4, 5 and 6 hours post oral administration to collect the gut microbial mass pellet. The drug absorbance by the gut microbiome was determined by pursuing the microbial lysate through RP-HPLC-UV. Total absorbance of sulpiride by the whole gut microbiome and drug absorbance per milligram of microbial pellet were found significantly higher at 4 hours post-administration as compared to all other groups. These results affirm the hypothesis that the structural homology between membrane transporters of the gut microbiome and intestinal epithelium of the host might play an important role in drug absorbance by gut microbes in an in vivo condition.

scholarly journals The Role of Melatonin on NLRP3 Inflammasome Activation in Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1020
Author(s):  
Burak Ibrahim Arioz ◽  
Emre Tarakcioglu ◽  
Melis Olcum ◽  
Sermin Genc
Keyword(s):  
Nlrp3 Inflammasome ◽  
Intracellular Signaling ◽  
Metabolic Diseases ◽  
Metabolic Stress ◽  
Clinical Importance ◽  
Rapid Identification ◽  
In Vivo Studies ◽  
Inflammasome Activation

NLRP3 inflammasome is a part of the innate immune system and responsible for the rapid identification and eradication of pathogenic microbes, metabolic stress products, reactive oxygen species, and other exogenous agents. NLRP3 inflammasome is overactivated in several neurodegenerative, cardiac, pulmonary, and metabolic diseases. Therefore, suppression of inflammasome activation is of utmost clinical importance. Melatonin is a ubiquitous hormone mainly produced in the pineal gland with circadian rhythm regulatory, antioxidant, and immunomodulatory functions. Melatonin is a natural product and safer than most chemicals to use for medicinal purposes. Many in vitro and in vivo studies have proved that melatonin alleviates NLRP3 inflammasome activity via various intracellular signaling pathways. In this review, the effect of melatonin on the NLRP3 inflammasome in the context of diseases will be discussed.

scholarly journals Comparing Donor- and Acceptor-Originated Exciton Dynamics in Non-Fullerene Acceptor Blend Polymeric Systems

Polymers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1770
Author(s):  
Chan Im ◽  
Sang-Woong Kang ◽  
Jeong-Yoon Choi ◽  
Jongdeok An
Keyword(s):  
Flexible Electronics ◽  
Transient Absorption ◽  
Film Formation ◽  
Transient Absorption Spectroscopy ◽  
Excitation Wavelength ◽  
Polymeric Systems ◽  
Donor And Acceptor ◽  
Novel Material ◽  
Spectrally Resolved ◽  
Energy Strategies

Non-fullerene type acceptors (NFA) have gained attention owing to their spectral extension that enables efficient solar energy capturing. For instance, the solely NFA-mediated absorbing region contributes to the photovoltaic power conversion efficiency (PCE) as high as ~30%, in the case of the solar cells comprised of fluorinated materials, PBDB-T-2F and ITIC-4F. This implies that NFAs must be able to serve as electron donors, even though they are conventionally assigned as electron acceptors. Therefore, the pathways of NFA-originated excitons need to be explored by the spectrally resolved photovoltaic characters. Additionally, excitation wavelength dependent transient absorption spectroscopy (TAS) was performed to trace the nature of the NFA-originated excitons and polymeric donor-originated excitons separately. Unique origin-dependent decay behaviors of the blend system were found by successive comparing of those solutions and pristine films which showed a dramatic change upon film formation. With the obtained experimental results, including TAS, a possible model describing origin-dependent decay pathways was suggested in the framework of reaction kinetics. Finally, numerical simulations based on the suggested model were performed to verify the feasibility, achieving reasonable correlation with experimental observables. The results should provide deeper insights in to renewable energy strategies by using novel material classes that are compatible with flexible electronics.

In vitro assessment of food-derived-glucose bioaccessibility and bioavailability in bicameral cell culture system

2020 ◽  
Vol 45 (5) ◽  
pp. 631-637
Author(s):  
Cansu Ozel-Tasci ◽  
Gozde Pilatin ◽  
Ozgur Edeer ◽  
Sukru Gulec
Keyword(s):  
Cell Culture ◽  
Culture System ◽  
Metabolic Diseases ◽  
Enzymatic Digestion ◽  
Cell Culture System ◽  
Culture Studies ◽  
Experimental Approaches ◽  
In Vitro Assessment

AbstractBackgroundFunctional foods can help prevent metabolic diseases, and it is essential to evaluate functional characteristics of foods through in vitro and in vivo experimental approaches.ObjectiveWe aimed to use the bicameral cell culture system combined with the in vitro digestion to evaluate glucose bioavailability.Materials and methodsCake, almond paste, and pudding were modified by adding fiber and replacing sugar with sweeteners and polyols. Digestion process was modeled in test tubes. Rat enterocyte cells (IEC-6) were grown in a bicameral cell culture system to mimic the physiological characteristics of the human intestine. The glucose bioaccessibility and cellular glucose efflux were measured by glucose oxidase assay.Results and discussionThe glucose bioaccessibilities of modified foods were significantly lower (cake: 2.6 fold, almond paste: 9.2 fold, pudding 2.8 fold) than the controls. Cellular glucose effluxes also decreased in the modified cake, almond paste, and pudding by 2.2, 4, and 2 fold respectively compared to their controls.ConclusionOur results suggest that combining in vitro enzymatic digestion with cell culture studies can be a practical way to test in vitro glucose bioaccessibility and bioavailability in functional food development.

scholarly journals BanLec-eGFP Chimera as a Tool for Evaluation of Lectin Binding to High-Mannose Glycans on Microorganisms

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 180
Author(s):  
Zorana Lopandić ◽  
Luka Dragačević ◽  
Dragan Popović ◽  
Uros Andjelković ◽  
Rajna Minić ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Lectin Binding ◽  
Three Dimensional ◽  
Data Bank ◽  
Salmonella Typhi ◽  
Excitation Wavelength ◽  
Protein Data Bank Entry ◽  
High Mannose

Fluorescently labeled lectins are useful tools for in vivo and in vitro studies of the structure and function of tissues and various pathogens such as viruses, bacteria, and fungi. For the evaluation of high-mannose glycans present on various glycoproteins, a three-dimensional (3D) model of the chimera was designed from the crystal structures of recombinant banana lectin (BanLec, Protein Data Bank entry (PDB): 5EXG) and an enhanced green fluorescent protein (eGFP, PDB 4EUL) by applying molecular modeling and molecular mechanics and expressed in Escherichia coli. BanLec-eGFP, produced as a soluble cytosolic protein of about 42 kDa, revealed β-sheets (41%) as the predominant secondary structures, with the emission peak maximum detected at 509 nm (excitation wavelength 488 nm). More than 65% of the primary structure was confirmed by mass spectrometry. Competitive BanLec-eGFP binding to high mannose glycans of the influenza vaccine (Vaxigrip®) was shown in a fluorescence-linked lectin sorbent assay (FLLSA) with monosaccharides (mannose and glucose) and wild type BanLec and H84T BanLec mutant. BanLec-eGFP exhibited binding to mannose residues on different strains of Salmonella in flow cytometry, with especially pronounced binding to a Salmonella Typhi clinical isolate. BanLec-eGFP can be a useful tool for screening high-mannose glycosylation sites on different microorganisms.

scholarly journals Xylitol enhances synthesis of propionate in the colon via cross-feeding of gut microbiota

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Shasha Xiang ◽  
Kun Ye ◽  
Mian Li ◽  
Jian Ying ◽  
Huanhuan Wang ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Lactobacillus Reuteri ◽  
Carbon Sources ◽  
Short Chain Fatty Acids ◽  
Microbial Composition ◽  
Key Enzymes ◽  
Rrna Sequencing ◽  
Phosphate Acetyltransferase

Abstract Background Xylitol, a white or transparent polyol or sugar alcohol, is digestible by colonic microorganisms and promotes the proliferation of beneficial bacteria and the production of short-chain fatty acids (SCFAs), but the mechanism underlying these effects remains unknown. We studied mice fed with 0%, 2% (2.17 g/kg/day), or 5% (5.42 g/kg/day) (weight/weight) xylitol in their chow for 3 months. In addition to the in vivo digestion experiments in mice, 3% (weight/volume) (0.27 g/kg/day for a human being) xylitol was added to a colon simulation system (CDMN) for 7 days. We performed 16S rRNA sequencing, beneficial metabolism biomarker quantification, metabolome, and metatranscriptome analyses to investigate the prebiotic mechanism of xylitol. The representative bacteria related to xylitol digestion were selected for single cultivation and co-culture of two and three bacteria to explore the microbial digestion and utilization of xylitol in media with glucose, xylitol, mixed carbon sources, or no-carbon sources. Besides, the mechanisms underlying the shift in the microbial composition and SCFAs were explored in molecular contexts. Results In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro. Cross-feeding, a relationship in which one organism consumes metabolites excreted by the other, was observed among Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol. At the molecular level, we revealed that xylitol dehydrogenase (EC 1.1.1.14), xylulokinase (EC 2.7.1.17), and xylulose phosphate isomerase (EC 5.1.3.1) were key enzymes in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Therefore, they are considered keystone bacteria in xylitol digestion. Also, xylitol affected the metabolic pathway of propionate, significantly promoting the transcription of phosphate acetyltransferase (EC 2.3.1.8) in Bifidobacterium and increasing the production of propionate. Conclusions Our results revealed that those key enzymes for xylitol digestion from different bacteria can together support the growth of micro-ecology, but they also enhanced the concentration of propionate, which lowered pH to restrict relative amounts of Escherichia and Staphylococcus. Based on the cross-feeding and competition among those bacteria, xylitol can dynamically balance proportions of the gut microbiome to promote enzymes related to xylitol metabolism and SCFAs.

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