A novel gut microbiome therapeutic derived from dietary polyphenols attenuates neuroinflammation
            in vivo
            in a model of C9orf72‐mediated frontotemporal dementia

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

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Sulpiride Serves, a Substrate for the Gut Microbiome

Dose-Response ◽

10.1177/1559325820987943 ◽

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.

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

Microbiome ◽

10.1186/s40168-021-01029-6 ◽

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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In vivo exploration of synaptic projections in frontotemporal dementia

Scientific Reports ◽

10.1038/s41598-021-95499-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Eric Salmon ◽

Mohamed Ali Bahri ◽

Alain Plenevaux ◽

Guillaume Becker ◽

Alain Seret ◽

...

Keyword(s):

Frontotemporal Dementia ◽

Input Function ◽

Parahippocampal Gyrus ◽

Exploratory Research ◽

Social Brain ◽

Synaptic Density ◽

Clinical Disorder ◽

Significant Difference ◽

The Right

AbstractThe purpose of this exploratory research is to provide data on synaptopathy in the behavioral variant of frontotemporal dementia (bvFTD). Twelve patients with probable bvFTD were compared to 12 control participants and 12 patients with Alzheimer’s disease (AD). Loss of synaptic projections was assessed with [18F]UCBH-PET. Total distribution volume was obtained with Logan method using carotid artery derived input function. Neuroimages were analyzed with SPM12. Verbal fluency, episodic memory and awareness of cognitive impairment were equally impaired in patients groups. Compared to controls, [18F]UCBH uptake tended to decrease in the right anterior parahippocampal gyrus of bvFTD patients. Loss of synaptic projections was observed in the right hippocampus of AD participants, but there was no significant difference in [18F]UCBH brain uptake between patients groups. Anosognosia for clinical disorder was correlated with synaptic density in the caudate nucleus and the anteromedial prefrontal cortex. This study suggests that synaptopathy in bvFTD targets the temporal social brain and self-referential processes.

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Isolation and structural elucidation of dimeric epigallocatechin-3-gallate autoxidation products and their antioxidant capacity

European Food Research and Technology ◽

10.1007/s00217-021-03846-3 ◽

2021 ◽

Author(s):

Julian Alfke ◽

Uta Kampermann ◽

Svetlana Kalinina ◽

Melanie Esselen

Keyword(s):

Antioxidant Capacity ◽

Antioxidant Properties ◽

Cd Spectroscopy ◽

Trolox Equivalent Antioxidant Capacity ◽

Published Data ◽

Dietary Polyphenols ◽

Cellular Effects ◽

The Impact

AbstractDietary polyphenols like epigallocatechin-3-gallate (EGCG)—which represents the most abundant flavan-3-ol in green tea—are subject of several studies regarding their bioactivity and health-related properties. On many occasions, cell culture or in vitro experiments form the basis of published data. Although the stability of these compounds is observed to be low, many reported effects are directly related to the parent compounds whereas the impact of EGCG degradation and autoxidation products is not yet understood and merely studied. EGCG autoxidation products like its dimers theasinensin A and D, “P2” and oolongtheanin are yet to be characterized in the same extent as their parental polyphenol. However, to investigate the bioactivity of autoxidation products—which would minimize the discrepancy between in vitro and in vivo data—isolation and structure elucidation techniques are urgently needed. In this study, a new protocol to acquire the dimers theasinensin A and D as well as oolongtheanin is depicted, including a variety of spectroscopic and quadrupole time-of-flight high-resolution mass spectrometric (qTOF-HRMS) data to characterize and assign these isolates. Through nuclear magnetic resonance (NMR) spectroscopy, polarimetry, and especially circular dichroism (CD) spectroscopy after enzymatic hydrolysis the complementary atropisomeric stereochemistry of the isolated theasinensins is illuminated and elucidated. Lastly, a direct comparison between the isolated EGCG autoxidation products and the monomer itself is carried out regarding their antioxidant properties featuring Trolox equivalent antioxidant capacity (TEAC) values. These findings help to characterize these products regarding their cellular effects and—which is of special interest in the flavonoid group—their redox properties.

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Plant polyphenols: free radical scavengers or chain-breaking antioxidants?

Biochemical Society Symposium ◽

10.1042/bss0610103 ◽

1995 ◽

Vol 61 ◽

pp. 103-116 ◽

Cited By ~ 117

Author(s):

Catherine Rice-Evans

Keyword(s):

Biological Effects ◽

Relative Effectiveness ◽

Antioxidant Properties ◽

Peroxyl Radicals ◽

Free Radical Scavengers ◽

Dietary Polyphenols ◽

Chain Breaking ◽

Lipid Peroxyl Radicals

There is increasing interest in the biological effects of tea- and wine-derived polyphenols and many studies in vitro and in vivo are demonstrating their antioxidant properties. Tea is a major source of dietary polyphenols and an even richer source of the flavanols, the catechins and catechin/gallate esters. Although there are limited studies on the bioavailability of the polyphenols, the absorption of flavanols in humans has been shown. The studies described in this chapter discuss the relative antioxidant potentials of the polyphenolic flavonoids in vitro against radicals generated in the aqueous phase in comparison with their relative effectiveness as antioxidants against propagating lipid peroxyl radicals, and how their activity influences that of α-tocopherol in low-density lipoproteins exposed to oxidative stress.

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The Effects of In Vivo Exposure to Copper Oxide Nanoparticles on the Gut Microbiome, Host Immunity, and Susceptibility to a Bacterial Infection in Earthworms

Nanomaterials ◽

10.3390/nano10071337 ◽

2020 ◽

Vol 10 (7) ◽

pp. 1337 ◽

Cited By ~ 2

Author(s):

Elmer Swart ◽

Jiri Dvorak ◽

Szabolcs Hernádi ◽

Tim Goodall ◽

Peter Kille ◽

...

Keyword(s):

Immune Responses ◽

Gut Microbiome ◽

Methodological Approach ◽

Copper Oxide Nanoparticles ◽

Mrna Levels ◽

Immune Genes ◽

Host Immune Responses ◽

Earthworm Gut ◽

Bacterium Bacillus

Nanomaterials (NMs) can interact with the innate immunity of organisms. It remains, however, unclear whether these interactions can compromise the immune functioning of the host when faced with a disease threat. Co-exposure with pathogens is thus a powerful approach to assess the immuno-safety of NMs. In this paper, we studied the impacts of in vivo exposure to a biocidal NM on the gut microbiome, host immune responses, and susceptibility of the host to a bacterial challenge in an earthworm. Eisenia fetida were exposed to CuO-nanoparticles in soil for 28 days, after which the earthworms were challenged with the soil bacterium Bacillus subtilis. Immune responses were monitored by measuring mRNA levels of known earthworm immune genes. Effects of treatments on the gut microbiome were also assessed to link microbiome changes to immune responses. Treatments caused a shift in the earthworm gut microbiome. Despite these effects, no impacts of treatment on the expression of earthworm immune markers were recorded. The methodological approach applied in this paper provides a useful framework for improved assessment of immuno-safety of NMs. In addition, we highlight the need to investigate time as a factor in earthworm immune responses to NM exposure.

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2581. An Invertebrate Model to Study Gut Microbiome Dysbiosis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2259 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S896-S897

Author(s):

Faris S Alnezary ◽

Tasnuva Rashid ◽

Khurshida Begum ◽

Travis J Carlson ◽

Anne J Gonzales-Luna ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Galleria Mellonella ◽

Nigella Sativa ◽

Gut Contents ◽

In Vivo Model ◽

Microbiota Composition ◽

Invertebrate Model ◽

Gut Microbiota Composition

Abstract Background Antimicrobials disrupt the gut microbiota by reducing gut microbiome diversity and quantity. Galleria mellonella provides an invertebrate model that is inexpensive, easy to maintain, and does not require specialized equipment. This study investigated the feasibility of using G. mellonella as an in vivo model to evaluate the effect of different antimicrobials on gut microbiota. Methods To determine baseline gut microbiota composition, the gut contents of G. mellonella were extracted and genomic DNA underwent shotgun meta-genomic sequencing. To determine the effect of infection and antibiotic use, 30 larvae were injected (left proleg) with ~1 × 105 colony-forming unit (cfu) of methicillin-resistant Staphylococcus aureus (MRSA) and were randomized 1:1:1 to treatment with vancomycin (20 mg/kg) or a natural antimicrobial (Nigella sativa seed oil, 70 mg/kg; NS oil), or a combination. The larvae were kept at 37°C post-infection and monitored daily for 72 hours for activity, extent of cocoon formation/growth, melanization, and survival. Two larvae from each group were randomly selected and homogenized with PBS as controls. After 24 hours of incubation, gut contents were extracted and plated for MRSA and Enterococcus cfu counts. Results Metagenomics analysis showed the gut microbiota composition of G. mellonella larvae was dominated by a subset of closely-related Enterococcus species. After 24 hours of exposure, mean Enterococcus counts were 4 × 103 cfu in the vancomycin arm and 6.2 × 104 cfu in the NS oil arm. Mean MRSA counts were 3.3 × 105 cfu in vancomycin arm and 1.5 × 104 cfu in NS oil arm. The combination of vancomycin and NS oil had higher Enterococcus counts than the vancomycin alone arm (6.3 × 104 cfu vs. 4 × 103 cfu, respectively), suggesting that NS oil may have a role in protecting the gut microbiota. Conclusion This study provides preliminary evidence to support the potential use of G. mellonella to assess the in vivo effect of a natural and synthetic antimicrobial on the gut microbiota. Disclosures All authors: No reported disclosures.

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