Editorial: Diet-microbe-host interactions in metabolic syndrome

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The Intricate Relationship between Diabetes, Diet and the Gut Microbiota

The most recent World Health Organization report revealed that the number of adults suffering from diabetes has almost quadrupled since 1980 to 422 million, thus drawing attention to the urgent need to step up prevention and treatment of this disease. This chronic ailment is often associated with serious complications such as increased risk of heart disease, stroke and kidney failure. In 2012 alone, diabetes lead to 1.5 million deaths. This dramatic rise is mainly due to the increased prevalence of type 2 diabetes and factors driving it include overweight and obesity. Novel studies in this area have advanced our understanding regarding the complex relationship between diet, gut microbiota and diabetes. Despite no clear microbiota signature is associated with diabetes, patients harbour a reduction of butyrate-producing species (Faecalibacterium prausnitzii, Roseburia intestinalis) as well as an increase in opportunistic pathogens. Furthermore, the functions of the gut microbiome (i.e., vitamin metabolism, transport of sugars, carbohydrate metabolism, short chain fatty acid (SCFA) synthesis, etc.) are also different in patients with type 2 diabetes, a fact that may significantly alter the course of disease. Diet is one of the most decisive factors that have an impact on the gut microbiome. Nutritional interventions using prebiotics (i.e., inulin-type fructans), polyphenols and arabinoxylans have been employed for the treatment of diabetes. Besides the shifts produced by these dietary components in the microbiome composition, it is worth mentioning their impact on host physiology through modulation of gut peptide production and glucose metabolism. The information presented within this chapter summarizes the most recent advances in the study of the microbiome-diet-diabetes interplay and analyses how these novel findings can be used in order to establish new therapeutic approaches for those with diabetes

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, 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

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

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

Carriage of ESBL-producing Enterobacterales in wastewater treatment plant workers and surrounding residents - the AWARE Study

To investigate whether wastewater treatment plant (WWTP) workers and residents living in close proximity to a WWTP have elevated carriage rates of ESBL-producing Enterobacterales, as compared to the general population. From 2018 to 2020, we carried out a cross-sectional study in Germany, the Netherlands, and Romania among WWTP workers (N = 344), nearby residents (living ≤ 300~m away from WWTPs; N = 431) and distant residents (living ≥ 1000~m away = reference group; N = 1165). We collected information on potential confounders via questionnaire. Culture of participants' stool samples was performed with ChromID®-ESBL agar plates and species identification with MALDI-TOF-MS. We used logistic regression to estimate the odds ratio (OR) for carrying ESBL-producing E. coli (ESBL-EC). Sensitivity analyses included stratification by country and interaction models using country as secondary exposure. Prevalence of ESBL-EC was 11% (workers), 29% (nearby residents), and 7% (distant residents), and higher in Romania (28%) than in Germany (7%) and the Netherlands (6%). Models stratified by country showed that within the Romanian population, WWTP workers are about twice as likely (aOR = 2.34, 95% CI: 1.22-4.50) and nearby residents about three times as likely (aOR = 3.17, 95% CI: 1.80-5.59) to be ESBL-EC carriers, when compared with distant residents. In stratified analyses by country, we found an increased risk for carriage of ESBL-EC in Romanian workers and nearby residents. This effect was higher for nearby residents than for workers, which suggests that, for nearby residents, factors other than the local WWTP could contribute to the increased carriage