Editorial: Diet-microbe-host interactions in metabolic syndrome

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Common themes in antimicrobial and anticancer drug resistance

Publication history: Accepted - 22 July 2022; Published - 8 August 2022.Antimicrobial and anticancer drug resistance represent two of the main global challenges for the public health, requiring immediate practical solutions. In line with this, we need a better understanding of the origins of drug resistance in prokaryotic and eukaryotic cells and the evolutionary processes leading to the occurrence of adaptive phenotypes in response to the selective pressure of therapeutic agents. The purpose of this paper is to present some of the analogies between the antimicrobial and anticancer drug resistance. Antimicrobial and anticancer drugs share common targets and mechanisms of action as well as similar mechanisms of resistance (e.g., increased drug efflux, drug inactivation, target alteration, persister cells’ selection, protection of bacterial communities/malignant tissue by an extracellular matrix, etc.). Both individual and collective stress responses triggered by the chemotherapeutic agent involving complex intercellular communication processes, as well as with the surrounding microenvironment, will be considered. The common themes in antimicrobial and anticancer drug resistance recommend the utility of bacterial experimental models for unraveling the mechanisms that facilitate the evolution and adaptation of malignant cells to antineoplastic drugs.This research was funded by CNFIS-FDI-2022-0675, UEFISCDI - PN-III-P4-PCE2021-1797, PN-III-P1-1.1-36PD-2019- 0499, Grant number 224/2021 and the Ministry of Research, Innovation, and Digitalization through Program 1—Development of the national R&D system, Subprogram 1.2—Institutional performance—Financing projects for excellence in RDI, Contract no. 41 PFE/30.12.2021

Dysbiosis, Tolerance, and Development of Autoimmune Diseases

The pathogenesis of autoimmune diseases (AIDS) is not only attributed to genetic susceptibility, but also to environmental factors, among which, those disturbing gut microbiota have attracted increasing attention lately. Healthy gut microbiota has beneficial effects on the development and activity of the immune system, playing a central role in peripheric tolerance. Compositional and functional changes in gut microbiota were reported in various AIDS, and increasing evidence suggests that disturbed gut microbiota contributes to their immunopathogenesis. Thyroid and intestinal diseases prevalently coexist—for instance, Hashimoto’s thyroiditis and Graves’ disease are the most common autoimmune thyroid diseases and often co-occur with celiac disease. This association can be at least explained by increased intestinal permeability, allowing antigens to cross the barrier more easily and activate the immune system. The passage of microbial antigens into the internal environment may break the self-tolerance, generating the production of autoantibodies and/or autoreactive T cells. In this chapter, we briefly present the roles of intestinal microbiota in human physiology, with a focus on the role of microbiota in immune tolerance

Effects of the Lipid Profile, Type 2 Diabetes and Medication on the Metabolic Syndrome—Associated Gut Microbiome

Publication history: Accepted - 4 July 2022; Published online - 6 July 2022Metabolic syndrome (MetSyn) is a major health problem affecting approximately 25% of the worldwide population. Since the gut microbiota is highly connected to the host metabolism, several recent studies have emerged to characterize the role of the microbiome in MetSyn development and progression. To this end, our study aimed to identify the microbiome patterns which distinguish MetSyn from type 2 diabetes mellitus (T2DM). We performed 16S rRNA amplicon sequencing on a cohort of 70 individuals among which 40 were MetSyn patients. The microbiome of MetSyn patients was characterised by reduced diversity, loss of butyrate producers (Subdoligranulum, Butyricicoccus, Faecalibacterium prausnitzii) and enrichment in the relative abundance of fungal populations. We also show a link between the gut microbiome and lipid metabolism in MetSyn. Specifically, low-density lipoproteins (LDL) and high-density lipoproteins (HDL) display a positive effect on gut microbial diversity. When interrogating the signature of gut microbiota in a subgroup of patients harbouring both MetSyn and T2DM conditions, we observed a significant increase in taxa such as Bacteroides, Clostridiales, and Erysipelotrichaceae. This preliminary study shows for the first time that T2DM brings unique signatures of gut microbiota in MetSyn patients. We also highlight the impact of metformin treatment on the gut microbiota. Metformin administration was linked to changes in Prevotellaceae, Rickenellaceae, and Clostridiales. Further research focusing on the microbiome-metabolome patterns is needed to clarify the exact association of various gut microbial communities with the progression of T2DM and the occurrence of various complications in MetSyn patientsThis research was funded by UEFISCDI, project ID PN-III-P1-1.1-36PD-2019-0499, Grant number 224/2021 and C1.2.PFE-CDI.2021-587

Attenuation of Vibrio parahaemolyticus Virulence Factors by a Mixture of Natural Antimicrobials.

Reducing acute mortality in aquatic crustaceans using natural alternatives to antibiotics has become a necessity, firstly for its positive impact on the aquaculture industry and, secondly, because the extensive use of antibiotics may lead to increased levels of drug resistance in pathogenic microorganisms. This study aimed to investigate the effect of a mixture of natural antimicrobials on the in vitro and in vivo virulence abilities of Type VI secretion system (T6SS)-positive Vibrio parahaemolyticus (A3 and D4), strains known as having potentially harmful health consequences for aquatic crustaceans and consumers. Herein, we report that a natural antimicrobial mixture (A3009) was capable of significantly reducing the virulence of V. parahaemolyticus strains A3 and D4 in an in vitro infection model, using the fish cell line CHSE-214, an effect which correlates with the bacterial downregulation of hcp1 and hcp2 gene expression and with the ability of the antimicrobial to efficiently retain low cytotoxic levels (p < 0.001). We show for the first time that a natural antimicrobial is able to significantly reduce the mortality of shrimps in a challenge experiment and is able to significantly attenuate H2O2 release during infection (p < 0.001), indicating that it could harbor positive intestinal redox balance effects

Dysbiosis in the Development of Type I Diabetes and Associated Complications: From Mechanisms to Targeted Gut Microbes Manipulation Therapies

Publication history: Accepted - 8 March 2021; Published online - 9 March 2021Globally, we are facing a worrying increase in type 1 diabetes mellitus (T1DM) incidence, with onset at younger age shedding light on the need to better understand the mechanisms of disease and step-up prevention. Given its implication in immune system development and regulation of metabolism, there is no surprise that the gut microbiota is a possible culprit behind T1DM pathogenesis. Additionally, microbiota manipulation by probiotics, prebiotics, dietary factors and microbiota transplantation can all modulate early host–microbiota interactions by enabling beneficial microbes with protective potential for individuals with T1DM or at high risk of developing T1DM. In this review, we discuss the challenges and perspectives of translating microbiome data into clinical practice. Nevertheless, this progress will only be possible if we focus our interest on developing numerous longitudinal, multicenter, interventional and double-blind randomized clinical trials to confirm their efficacy and safety of these therapeutic approachesThis research was funded by UEFISCDI, project ID PN-III-P1-1.1-PD-2019-0499, grant number 224/2021

The in vitro and in vivo anti-virulent effect of organic acid mixtures against Eimeria tenella and Eimeria bovis.

Eimeria tenella and Eimeria bovis are complex parasites responsible for the condition of coccidiosis, that invade the animal gastrointestinal intestinal mucosa causing severe diarrhoea, loss of appetite or abortions, with devastating impacts on the farming industry. The negative impacts of these parasitic infections are enhanced by their role in promoting the colonisation of the gut by common foodborne pathogens. The aim of this study was to test the anti-Eimeria efficacy of maltodextrin, sodium chloride, citric acid, sodium citrate, silica, malic acid, citrus extract, and olive extract individually, in vitro and in combination, in vivo. Firstly, in vitro infection models demonstrated that antimicrobials reduced (p < 0.05), both singly and in combination (AG), the ability of E. tenella and E. bovis to infect MDBK and CLEC-213 epithelial cells, and the virulence reduction was similar to that of the anti-coccidial drug Robenidine. Secondly, using an in vivo broiler infection model, we demonstrated that AG reduced (p = 0.001) E. tenella levels in the caeca and excreted faeces, reduced inflammatory oxidative stress, improved the immune response through reduced ROS, increased Mn-SOD and SCFA levels. Levels of IgA and IgM were significantly increased in caecal tissues of broilers that received 0.5% AG and were associated with improved (p < 0.0001) tissue lesion scores. A prophylactic approach increased the anti-parasitic effect in vivo, and results indicated that administration from day 0, 5 and 10 post-hatch reduced tissue lesion scores (p < 0.0001) and parasite excretion levels (p = 0.002). Conclusively, our in vitro and in vivo results demonstrate that the natural antimicrobial mixture (AG) reduced parasitic infections through mechanisms that reduced pathogen virulence and attenuated host inflammatory events

Wastewater treatment plants, an “escape gate” for ESCAPE pathogens

Antibiotics are an essential tool of modern medicine, contributing to significantly decreasing mortality and morbidity rates from infectious diseases. However, persistent misuse of these drugs has accelerated the evolution of antibiotic resistance, negatively impacting clinical practice. The environment contributes to both the evolution and transmission of resistance. From all anthropically polluted aquatic environments, wastewater treatment plants (WWTPs) are probably the main reservoirs of resistant pathogens. They should be regarded as critical control points for preventing or reducing the release of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic-resistance genes (ARGs) into the natural environment. This review focuses on the fate of the pathogens Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae spp. (ESCAPE) in WWTPs. All ESCAPE pathogen species, including high-risk clones and resistance determinants to last-resort antibiotics such as carbapenems, colistin, and multi-drug resistance platforms, were detected in wastewater. The whole genome sequencing studies demonstrate the clonal relationships and dissemination of Gram-negative ESCAPE species into the wastewater via hospital effluents and the enrichment of virulence and resistance determinants of S. aureus and enterococci in WWTPs. Therefore, the efficiency of different wastewater treatment processes regarding the removal of clinically relevant ARB species and ARGs, as well as the influence of water quality factors on their performance, should be explored and monitored, along with the development of more effective treatments and appropriate indicators (ESCAPE bacteria and/or ARGs). This knowledge will allow the development of quality standards for point sources and effluents to consolidate the WWTP barrier role against the environmental and public health AR threats

The Antioxidant Effect of Natural Antimicrobials in Shrimp Primary Intestinal Cells Infected with Nematopsis messor.

Nematopsis messor infections severely impact on shrimp's health with devastating economic consequences on shrimp farming. In a shrimp primary intestinal cells (SGP) model of infection, a sub-inhibitory concentration (0.5%) of natural antimicrobials (Aq) was able to reduce the ability of N. messor to infect (p &lt; 0.0001). To prevent N. messor infection of SGP cells, Aq inhibits host actin polymerization and restores tight junction integrity (TEER) and the expression of Zo-1 and occluding. The oxidative burst, caused by N. messor infection, is attenuated by Aq through the inhibition of NADPH-produced H2O2. Simultaneous to the reduction in H2O2 released, the activity of catalase (CAT) and superoxide dismutase (SOD) were also significantly increase (p &lt; 0.0001). The antimicrobial mixture inactivates the ERK signal transduction pathway by tyrosine dephosphorylation and reduces the expression of DCR2, ALF-A, and ALF-C antimicrobial peptides. The observed in vitro results were also translated in vivo, whereby the use of a shrimp challenge test, we show that in N. messor infected shrimp the mortality rate was 68% compared to the Aq-treated group where the mortality rate was maintained at 14%. The significant increase in CAT and SOD activity in treated and infected shrimp suggested an in vivo antioxidant role for Aq. In conclusion, our study shows that Aq can efficiently reduce N. messor colonization of shrimp's intestinal cells in vitro and in vivo and the oxidative induced cellular damage, repairs epithelial integrity, and enhances gut immunity