Enterotoxigenic and Enterohemorrhagic <i>Escherichia coli</i>: Survival and Modulation of Virulence in the Human Gastrointestinal Tract

Enterotoxigenic Escherichia coli (ETEC) and Enterohemorrhagic Escherichia coli (EHEC) are major food‐ and water‐borne pathogens that constitute a serious public health threat in low‐income and developed countries, respectively. Survival and expression of virulence genes in the human digestive tract are key features in bacterial pathogenesis, but the mechanisms behind these processes remain largely unknown due to obvious prohibition of human studies. Use of well‐controlled and multi‐parametric in vitro models can aid in addressing knowledge gaps in ETEC and EHEC pathogenesis. After a general description of the physiopathology of ETEC and EHEC infections, this chapter will give an overview of all the in vitro studies that have investigated the effect of the main physicochemical and biotic parameters of the human gut on pathogen survival and expression of virulence factors. We bring a picture of how ETEC and EHEC are able to adapt to each of the successive environments of the human gastrointestinal tract by reading many cues provided by both the host and the gut microbiota

Modulation of Enterohaemorrhagic Escherichia coli Survival and Virulence in the human Gastrointestinal Tract

Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen responsible for human diseases ranging from diarrhoea to life-threatening complications. Survival of the pathogen and modulation of virulence gene expression along the human gastrointestinal tract (GIT) are key features in bacterial pathogenesis, but remain poorly described, due to a paucity of relevant model systems. This review will provide an overview of the in vitro and in vivo studies investigating the effect of abiotic (e.g., gastric acid, bile, low oxygen concentration or fluid shear) and biotic (e.g., gut microbiota, short chain fatty acids or host hormones) parameters of the human gut on EHEC survival and/or virulence (especially in relation with motility, adhesion and toxin production). Despite their relevance, these studies display important limitations considering the complexity of the human digestive environment. These include the evaluation of only one single digestive parameter at a time, lack of dynamic flux and compartmentalization, and the absence of a complex human gut microbiota. In a last part of the review, we will discuss how dynamic multi-compartmental in vitro models of the human gut represent a novel platform for elucidating spatial and temporal modulation of EHEC survival and virulence along the GIT, and provide new insights into EHEC pathogenesis

From Chihuahua to Saint-Bernard: how did digestion and microbiota evolve with dog sizes

Health and well-being of dogs are of paramount importance to their owners. Digestion plays a key role in dog health, involving physicochemical, mechanical and microbial actors. However, decades of breeding selection led to various dog sizes associated with different digestive physiology and disease sensitivity. Developing new products requires the consideration of all the multi-faceted aspects of canine digestion, the evaluation of food digestibility, drug release and absorption in the gut. This review paper provides an exhaustive literature survey on canine digestive physiology, focusing on size effect on anatomy and digestive parameters, with graphical representation of data classified as “small”, “medium” and “large” dogs. Despite the huge variability between protocols and animals, interesting size effects on gastrointestinal physiology were highlighted, mainly related to the colonic compartment. Colonic measurements, transit time permeability, fibre degradation, faecal short-chain fatty acid concentration and faecal water content increase while faecal bile acid concentration decreases with body size. A negative correlation between body weight and Proteobacteria relative abundance was observed suggesting an effect of dog body size on faecal microbiota. This paper gathers helpful in vivo data for academics and industrials and supports the development of new food and pharma products to move towards canine personalized nutrition and health

Interactions with M Cells and Macrophages as Key Steps in the Pathogenesis of Enterohemorragic Escherichia coli Infections

Enterohemorrhagic Escherichia coli (EHEC) are food-borne pathogens that can cause serious infections ranging from diarrhea to hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS). Translocation of Shiga-toxins (Stx) from the gut lumen to underlying tissues is a decisive step in the development of the infection, but the mechanisms involved remain unclear. Many bacterial pathogens target the follicle-associated epithelium, which overlies Peyer's patches (PPs), cross the intestinal barrier through M cells and are captured by mucosal macrophages. Here, translocation across M cells, as well as survival and proliferation of EHEC strains within THP-1 macrophages were investigated using EHEC O157:H7 reference strains, isogenic mutants, and 15 EHEC strains isolated from HC/HUS patients. We showed for the first time that E. coli O157:H7 strains are able to interact in vivo with murine PPs, to translocate ex vivo through murine ileal mucosa with PPs and across an in vitro human M cell model. EHEC strains are also able to survive and to produce Stx in macrophages, which induce cell apoptosis and Stx release. In conclusion, our results suggest that the uptake of EHEC by M cells and underlying macrophages in the PP may be a critical step in Stx translocation and release in vivo. A new model for EHEC infection in humans is proposed that could help in a fuller understanding of EHEC-associated diseases

Experimental models to study intestinal microbes-mucus interactions in health and disease

A close symbiotic relationship exists between the intestinal microbiota and its host. A critical component of gut homeostasis is the presence of a mucus layer covering the gastrointestinal tract. Mucus is a viscoelastic gel at the interface between the luminal content and the host tissue that provides a habitat to the gut microbiota and protects the intestinal epithelium. The review starts by setting up the biological context underpinning the need for experimental models to study gut bacteria-mucus interactions in the digestive environment. We provide an overview of the structure and function of intestinal mucus and mucins, their interactions with intestinal bacteria (including commensal, probiotics and pathogenic microorganisms) and their role in modulating health and disease states. We then describe the characteristics and potentials of experimental models currently available to study the mechanisms underpinning the interaction of mucus with gut microbes, including in vitro, ex vivo and in vivo models. We then discuss the limitations and challenges facing this field of research

A polyphenol-rich plant extract prevents hypercholesterolemia and modulates gut microbiota in western diet-fed mice

IntroductionTotum-070 is a combination of five plant extracts enriched in polyphenols to target hypercholesterolemia, one of the main risk factors for cardiovascular diseases. The aim of this study was to investigate the effects of Totum-070 on cholesterol levels in an animal model of diet-induced hypercholesterolemia.MethodsC57BL/6JOlaHsd male mice were fed a Western diet and received Totum-070, or not, by daily gavage (1g/kg and 3g/kg body weight) for 6 weeks.ResultsThe Western diet induced obesity, fat accumulation, hepatic steatosis and increased plasma cholesterol compared with the control group. All these metabolic perturbations were alleviated by Totum-070 supplementation in a dose-dependent manner. Lipid excretion in feces was higher in mice supplemented with Totum-070, suggesting inhibition of intestinal lipid absorption. Totum-070 also increased the fecal concentration of short chain fatty acids, demonstrating a direct effect on intestinal microbiota.DiscussionThe characterization of fecal microbiota by 16S amplicon sequencing showed that Totum-070 supplementation modulated the dysbiosis associated with metabolic disorders. Specifically, Totum-070 increased the relative abundance of Muribaculum (a beneficial bacterium) and reduced that of Lactococcus (a genus positively correlated with increased plasma cholesterol level). Together, these findings indicate that the cholesterol-lowering effect of Totum-070 bioactive molecules could be mediated through multiple actions on the intestine and gut microbiota

Extending in vitro digestion models to specific human populations: Perspectives, practical tools and bio-relevant information

[EN] Background In vitro digestion models show great promise in facilitating the rationale design of foods. This paper provides a look into the current state of the art and outlines possible future paths for developments of digestion models recreating the diverse physiological conditions of specific groups of the human population. Scope and approach Based on a collective effort of experts, this paper outlines considerations and parameters needed for development of new in vitro digestion models, e.g. gastric pH, enzymatic activities, gastric emptying rate and more. These and other parameters are detrimental to the adequate development of in vitro models that enable deeper insight into matters of food luminal breakdown as well as nutrient and nutraceutical bioaccessibility. Subsequently, we present an overview of some new and emerging in vitro digestion models mirroring the gastro-intestinal conditions of infants, the elderly and patients of cystic fibrosis or gastric bypass surgery. Key findings and conclusions This paper calls for synchronization, harmonization and validation of potential developments in in vitro digestion models that would greatly facilitate manufacturing of foods tailored or even personalized, to a certain extent, to various strata of the human population.Shani-Levi, C.; Alvito, P.; Andrés Grau, AM.; Assunção, R.; Barbera, R.; Blanquet-Diot, S.; Bourlieu, C.... (2017). Extending in vitro digestion models to specific human populations: Perspectives, practical tools and bio-relevant information. Trends in Food Science & Technology. 60:52-63. https://doi.org/10.1016/j.tifs.2016.10.017S52636

In vitro models of the human gastro-intestinal tract : potential and challenges in the pharma field

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Modèles in vitro de l’écosystème intestinal humain : potentiels, applications à l’évaluation de nouvelles stratégies ciblant le microbiote et futurs challenges

International audienc