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The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (29 February 2020) | Viewed by 40578

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Prof. Dr. David Kitts

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Guest Editor

Food, Nutrition, and Health Program, Faculty of Land and Food Systems, The University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada
Interests: food chemistry; toxicology; gut health; bioactive assessment models
Special Issues, Collections and Topics in MDPI journals

Dr. Ningjian Liang

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Food, Nutrition, and Health Program, Faculty of Land and Food Systems, The University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada
Interests: phytochemicals, antioxidant oxidative stress, redox biology, inflammation, foodborne pathogens

Special Issue Information

Dear Colleagues,

Current research in molecular nutrition and toxicology aims to investigate the physiological role of nutrients and food bioactives on human health status, directed specifically at molecular and cellular levels. Many nutrients and dietary bioactives exert cellular effects by interacting with signal transduction mechanisms. Similarly, factors that can control the onset of food-borne pathogens involve molecular homoestatic processes. Elucidating the mechanisms that underly the activities of nutrients, food bioactives and/or pathogens at the molecular level has become recognized as a first principle to understand how physiological function is modified to prevent disease and food-borne illness.

Although a vast volume of research is already available in this area, there still remains significant gaps in our knowledge that require investigation regarding molecular responses to a bioactive phytochemicals or food-borne pathogens. This Special Issue invites the submission of manuscripts, original research, or reviews of the scientific literature that are focused on novel findings in: 1) the molecular–cellular mechanisms that involve gene–nutrient interactions and the prevention of disease, 2) the use of toxins as informative tools with which to study signal transduction and usage as potential therapeutics, 3). the molecular mechanisms involved in the action of food-borne pathogens with emphasis on the detection and prevention of food-related illnesses.

Prof. Dr. David Kitts
Dr. Ningjian Liang
Guest Editors

Manuscript Submission Information

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Keywords

nutrients
bioactives
phytochemicals
food-borne pathogens
transcription factor signaling
redox balance
chronic inflammation
cell based vs animal models
disease prevention

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Published Papers (9 papers)

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Research

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13 pages, 1483 KiB

Open AccessArticle

Prevalence of an Intestinal ST40 Enterococcus faecalis over Other E. faecalis Strains in the Gut Environment of Mice Fed Different High Fat Diets

by Beatriz Sánchez, Antonio Cobo, Marina Hidalgo, Ana M. Martínez-Rodríguez, Isabel Prieto, Antonio Gálvez and Magdalena Martínez-Cañamero

Int. J. Mol. Sci. 2020, 21(12), 4330; https://doi.org/10.3390/ijms21124330 - 18 Jun 2020

Cited by 3 | Viewed by 2256

Abstract

E. faecalis is a commensal bacterium with specific strains involved in opportunistic and nosocomial infections. Therefore, it is important to know how the strains of this species are selected in the gut. In this study, fifteen E. faecalis strains, isolated over twelve weeks from the faeces of mice fed standard chow or one of three high fat diets enriched with extra virgin olive oil, refined olive oil or butter were subjected to a genetic “Multilocus Sequence Typing” study that revealed the presence of mainly two genotypes, ST9 and ST40, the latter one prevailing at the end of the research. A V3–V5 sequence comparison of the predominant ST40 strain (12B3-5) in a metagenomic study showed that this sequence was the only E. faecalis present in the mouse cohort after twelve weeks. The strain was subjected to a comparative proteomic study with a ST9 strain by 2D electrophoresis and mass spectrometry. After comparing the results with a E. faecalis database, unshared entries were compared and 12B3-5 showed higher antimicrobial production as well as greater protection from environmental factors such as xenobiotics, oxidative stress and metabolite accumulation, which could be the reason for its ability to outcompete other possible rivals in an intestinal niche. Full article

(This article belongs to the Special Issue The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms)

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14 pages, 861 KiB

Open AccessArticle

Bacteriophage-Insensitive Mutants of Antimicrobial-Resistant Salmonella Enterica are Altered in their Tetracycline Resistance and Virulence in Caco-2 Intestinal Cells

by Karen Fong, Kaiwen Mu, Jean-Guillaume Rheault, Roger C. Levesque, David D. Kitts, Pascal Delaquis, Lawrence Goodridge and Siyun Wang

Int. J. Mol. Sci. 2020, 21(5), 1883; https://doi.org/10.3390/ijms21051883 - 10 Mar 2020

Cited by 13 | Viewed by 4401

Abstract

Bacteriophages have shown promise as therapeutic alternatives to antibiotics for the control of infectious bacteria, including the human pathogen Salmonella. However, the development of effective phage-based applications requires the elucidation of key interactions between phages and target hosts, particularly since host resistance to phage is inevitable. Little is known about the alteration of host phenotypes following the development of resistance to phage. The aim of this study is to evaluate the antibiotic susceptibility and virulence of a Salmonella isolate following the development of resistance to bacteriophage SI1. We observed enhanced susceptibility to tetracycline and decreased invasion capacity in a differentiated Caco-2 intestinal cell line. Whole genome sequence analysis revealed an array of mutations, most notably, truncations in vgrG1_2, a core gene involved in Type VI secretion and mutations in the lipopolysaccharide, thereby indicating the plausible attachment site of phage SI1. These findings shed light on understanding the underlying mechanism for phage immunity within the host. Importantly, we reveal an associated genetic cost to the bacterial host with developing resistance to phages. Taken together, these results will aid in advancing strategies to delay or eliminate the development of host resistance when designing informed phage-based antimicrobials. Full article

(This article belongs to the Special Issue The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms)

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16 pages, 4623 KiB

Open AccessArticle

The Intraocular Pressure-Lowering Effect of Persimmon leaves (Diospyros kaki) in a Mouse Model of Glaucoma

by Hong Ryul Ahn, Jae Wook Yang, Jee Young Kim, Chang Yong Lee, Tae-Jin Kim and Sang Hoon Jung

Int. J. Mol. Sci. 2019, 20(21), 5268; https://doi.org/10.3390/ijms20215268 - 23 Oct 2019

Cited by 10 | Viewed by 4184

Abstract

The aim of this study was to evaluate the pharmacological efficacy of persimmon leaves in two glaucoma models, microbeads-induced ocular hypertension (OHT) and DBA/2 mouse. Thus, we demonstrated that Ethanol Extract of Diospyros kaki (EEDK) reduced elevated intraocular pressure (IOP) in both mouse models of glaucoma by measurements with a tonometer. In particular, we revealed that retinal ganglion cell loss and optic nerve damage caused by IOP elevation were markedly diminished as assessed by TUNEL assay, H&E staining, and fluorescent staining, while the expression of soluble guanylate cyclase (sGCα-1) increased, when EEDK was administered, as revealed by western blot. Moreover, the b-wave magnitude indicating functional scotopic vision was significantly improved in EEDK-administered DBA/2 mice during the 10-week follow-up study, as observed with electroretinography. Collectively, our results suggested that EEDK could be an effective therapeutic and IOP-lowering agent for preventing and treating retinal degenerative diseases such as glaucoma. Full article

(This article belongs to the Special Issue The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms)

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16 pages, 396 KiB

Open AccessArticle

Influence of the Type of Diet on the Incidence of Pathogenic Factors and Antibiotic Resistance in Enterococci Isolated from Faeces in Mice

by Beatriz Sánchez, Antonio Cobo, Marina Hidalgo, Ana M. Martínez-Rodríguez, Isabel Prieto, Antonio Gálvez and Magdalena Martínez-Cañamero

Int. J. Mol. Sci. 2019, 20(17), 4290; https://doi.org/10.3390/ijms20174290 - 2 Sep 2019

Cited by 8 | Viewed by 2209

Abstract

A comparative study on potential risks was carried out in a collection of 50 enterococci isolated from faeces of mice fed a standard or a high-fat diet enriched with extra virgin olive oil, refined olive oil or butter, at the beginning, after six weeks and after twelve weeks of experiments. Strains were biochemically assessed and genetically characterized. E. faecalis and E. casseliflavus were the most frequently isolated species in any diet and time points. Apart from the fact of not having isolated any strain from the virgin olive oil group during the last balance, we found statistically significant differences

(p < 0.05)

among the diets in the percentage of antibiotic resistance and in the presence of the enterococcal surface protein gene (esp), as well as a tendency

(p < 0.1)

for the presence of the tyrosine decarboxylase gene (tdc) to increase over time in the group of isolates from the standard diet. When the resistance of the strains to virgin or refined olive oil was studied, only the group of enterococci from high fat diets showed a significantly higher percentage of resistance to refined olive oil

(p < 0.05)

, while both types of oil equally inhibited those isolated from the standard diet

(p > 0.05)

. Full article

(This article belongs to the Special Issue The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms)

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19 pages, 4363 KiB

Open AccessArticle

Amelioration of Enterotoxigenic Escherichia coli-Induced Intestinal Barrier Disruption by Low-Molecular-Weight Chitosan in Weaned Pigs is Related to Suppressed Intestinal Inflammation and Apoptosis

by Jin Wan, Jiao Zhang, Guozhong Wu, Daiwen Chen, Bing Yu, Zhiqing Huang, Yuheng Luo, Ping Zheng, Junqiu Luo, Xiangbing Mao, Jie Yu and Jun He

Int. J. Mol. Sci. 2019, 20(14), 3485; https://doi.org/10.3390/ijms20143485 - 16 Jul 2019

Cited by 39 | Viewed by 3918

Abstract

Enterotoxigenic Escherichia coli (ETEC) infection destroys the intestinal barrier integrity, in turn, disrupting intestinal homoeostasis. Low-molecular-weight chitosan (LMWC) is a water-soluble chitosan derivative with versatile biological properties. Herein, we examined whether LMWC could relieve ETEC-induced intestinal barrier damage in weaned pigs. Twenty-four weaned pigs were allotted to three treatments: (1) non-infected control; (2) ETEC-infected control; and (3) ETEC infection + LMWC supplementation (100 mg/kg). On day 12, pigs in the infected groups were administered 100 mL of ETEC at 2.6 × 10⁹ colony-forming units/mL to induce intestinal barrier injury. Three days later, serum samples were obtained from all pigs, which were then slaughtered to collect intestinal samples. We evidenced that LMWC not only increased (P < 0.05) the occludin protein abundance but also decreased (P < 0.05) the interleukin-6, tumour necrosis factor-α and mast cell tryptase contents, and the apoptotic epithelial cell percentages, in the small intestine of ETEC-infected pigs. Furthermore, LMWC down-regulated (P < 0.05) the small intestinal expression levels of critical inflammatory- and apoptotic-related genes, such as Toll-like receptor 4 (TLR4) and tumour necrosis factor receptor 1 (TNFR1), as well as the intra-nuclear nuclear factor-κB (NF-κB) p65 protein abundance, in the ETEC-infected pigs. Our study indicated a protective effect of LMWC on ETEC-triggered intestinal barrier disruption in weaned pigs, which involves the repression of intestinal inflammatory responses via blocking the TLR4/NF-κB signalling pathway and the depression of epithelial cell death via TNFR1-dependent apoptosis. Full article

(This article belongs to the Special Issue The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms)

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15 pages, 1141 KiB

Open AccessArticle

Consumption of Nitrate-Rich Beetroot Juice with or without Vitamin C Supplementation Increases the Excretion of Urinary Nitrate, Nitrite, and N-nitroso Compounds in Humans

by Julia E. Berends, Lauri M.M. van den Berg, Martina A. Guggeis, Nikki F.T. Henckens, Israt J. Hossein, Minke E.J.R. de Joode, Hossy Zamani, Kirsten A.A.J. van Pelt, Nicky A. Beelen, Gunter G. Kuhnle, Theo M.C.M. de Kok and Simone G.J. Van Breda

Int. J. Mol. Sci. 2019, 20(9), 2277; https://doi.org/10.3390/ijms20092277 - 8 May 2019

Cited by 27 | Viewed by 9004

Abstract

Consumption of nitrate-rich beetroot juice (BRJ) by athletes induces a number of beneficial physiological health effects, which are linked to the formation of nitric oxide (NO) from nitrate. However, following a secondary pathway, NO may also lead to the formation of N-nitroso compounds (NOCs), which are known to be carcinogenic in 39 animal species. The extent of the formation of NOCs is modulated by various other dietary factors, such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion. In a randomized, controlled trial, 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week. A significant increase of urinary apparent total N-nitroso Compounds (ATNC) was found after one dose (5 to 47 nmol/mmol: p < 0.0001) and a further increase was found after seven consecutive doses of BRJ (104 nmol/mmol: p < 0.0001). Vitamin C supplementation inhibited ATNC increase after one dose (16 compared to 72 nmol/mmol, p < 0.01), but not after seven daily doses. This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs. In order to protect athlete’s health, it is therefore important to be cautious with chronic use of BRJ to enhance sports performances. Full article

(This article belongs to the Special Issue The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms)

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Review

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17 pages, 496 KiB

Open AccessReview

The Effects of Maternal and Postnatal Dietary Methyl Nutrients on Epigenetic Changes that Lead to Non-Communicable Diseases in Adulthood

by Raniru S. Randunu and Robert F. Bertolo

Int. J. Mol. Sci. 2020, 21(9), 3290; https://doi.org/10.3390/ijms21093290 - 6 May 2020

Cited by 29 | Viewed by 4219

Abstract

The risk for non-communicable diseases in adulthood can be programmed by early nutrition. This programming is mediated by changes in expression of key genes in various metabolic pathways during development, which persist into adulthood. These developmental modifications of genes are due to epigenetic alterations in DNA methylation patterns. Recent studies have demonstrated that DNA methylation can be affected by maternal or early postnatal diets. Because methyl groups for methylation reactions come from methionine cycle nutrients (i.e., methionine, choline, betaine, folate), deficiency or supplementation of these methyl nutrients can directly change epigenetic regulation of genes permanently. Although many studies have described the early programming of adult diseases by maternal and infant nutrition, this review discusses studies that have associated early dietary methyl nutrient manipulation with direct effects on epigenetic patterns that could lead to chronic diseases in adulthood. The maternal supply of methyl nutrients during gestation and lactation can alter epigenetics, but programming effects vary depending on the timing of dietary intervention, the type of methyl nutrient manipulated, and the tissue responsible for the phenotype. Moreover, the postnatal manipulation of methyl nutrients can program epigenetics, but more research is needed on whether this approach can rescue maternally programmed offspring. Full article

(This article belongs to the Special Issue The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms)

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21 pages, 1030 KiB

Open AccessReview

Bioactive Polyphenols and Neuromodulation: Molecular Mechanisms in Neurodegeneration

by Francesco Di Meo, Anna Valentino, Orsolina Petillo, Gianfranco Peluso, Stefania Filosa and Stefania Crispi

Int. J. Mol. Sci. 2020, 21(7), 2564; https://doi.org/10.3390/ijms21072564 - 7 Apr 2020

Cited by 82 | Viewed by 5858

Abstract

The interest in dietary polyphenols in recent years has greatly increased due to their antioxidant bioactivity with preventive properties against chronic diseases. Polyphenols, by modulating different cellular functions, play an important role in neuroprotection and are able to neutralize the effects of oxidative stress, inflammation, and apoptosis. Interestingly, all these mechanisms are involved in neurodegeneration. Although polyphenols display differences in their effectiveness due to interindividual variability, recent studies indicated that bioactive polyphenols in food and beverages promote health and prevent age-related cognitive decline. Polyphenols have a poor bioavailability and their digestion by gut microbiota produces active metabolites. In fact, dietary bioactive polyphenols need to be modified by microbiota present in the intestine before being absorbed, and to exert health preventive effects by interacting with cellular signalling pathways. This literature review includes an evaluation of the literature in English up to December 2019 in PubMed and Web of Science databases. A total of 307 studies, consisting of research reports, review articles and articles were examined and 146 were included. The review highlights the role of bioactive polyphenols in neurodegeneration, with a particular emphasis on the cellular and molecular mechanisms that are modulated by polyphenols involved in protection from oxidative stress and apoptosis prevention. Full article

(This article belongs to the Special Issue The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms)

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18 pages, 689 KiB

Open AccessReview

Molecular Mechanisms That Define Redox Balance Function in Pathogen-Host Interactions—Is There a Role for Dietary Bioactive Polyphenols?

by Kaiwen Mu, Danni Wang and David D. Kitts

Int. J. Mol. Sci. 2019, 20(24), 6222; https://doi.org/10.3390/ijms20246222 - 10 Dec 2019

Cited by 9 | Viewed by 3863

Abstract

To ensure a functional immune system, the mammalian host must detect and respond to the presence of pathogenic bacteria during infection. This is accomplished in part by generating reactive oxygen species (ROS) that target invading bacteria; a process that is facilitated by NADPH oxidase upregulation. Thus, bacterial pathogens must overcome the oxidative burst produced by the host innate immune cells in order to survive and proliferate. In this way, pathogenic bacteria develop virulence, which is related to the affinity to secrete effector proteins against host ROS in order to facilitate microbial survival in the host cell. These effectors scavenge the host generated ROS directly, or alternatively, manipulate host cell signaling mechanisms designed to benefit pathogen survival. The redox-balance of the host is important for the regulation of cell signaling activities that include mitogen-activated protein kinase (MAPK), p21-activated kinase (PAK), phosphatidylinositol 3-kinase (PI3K)/Akt, and nuclear factor κB (NF-κB) pathways. An understanding of the function of pathogenic effectors to divert host cell signaling is important to ascertain the mechanisms underlying pathogen virulence and the eventual host–pathogen relationship. Herein, we examine the effectors produced by the microbial secretion system, placing emphasis on how they target molecular signaling mechanisms involved in a host immune response. Moreover, we discuss the potential impact of bioactive polyphenols in modulating these molecular interactions that will ultimately influence pathogen virulence. Full article

(This article belongs to the Special Issue The Cellular and Molecular Mechanisms of Both Food Bioactives and Pathogens in Living Organisms)

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