The intestinal microbiota plays an important role in regulating gastrointestinal (GI) physiology in part through interactions with the enteric nervous system (ENS). Alterations in the gut microbiome ...frequently occur together with disturbances in enteric neural control in pathophysiological conditions. However, the mechanisms by which the microbiota regulates GI function and the structure of the ENS are incompletely understood. Using a mouse model of antibiotic (Abx)-induced bacterial depletion, we sought to determine the molecular mechanisms of microbial regulation of intestinal function and the integrity of the ENS. Spontaneous reconstitution of the Abx-depleted microbiota was used to assess the plasticity of structure and function of the GI tract and ENS. Microbiota-dependent molecular mechanisms of ENS neuronal survival and neurogenesis were also assessed.
Adult male and female Abx-treated mice exhibited alterations in GI structure and function, including a longer small intestine, slower transit time, increased carbachol-stimulated ion secretion, and increased intestinal permeability. These alterations were accompanied by the loss of enteric neurons in the ileum and proximal colon in both submucosal and myenteric plexuses. A reduction in the number of enteric glia was only observed in the ileal myenteric plexus. Recovery of the microbiota restored intestinal function and stimulated enteric neurogenesis leading to increases in the number of enteric glia and neurons. Lipopolysaccharide (LPS) supplementation enhanced neuronal survival alongside bacterial depletion, but had no effect on neuronal recovery once the Abx-induced neuronal loss was established. In contrast, short-chain fatty acids (SCFA) were able to restore neuronal numbers after Abx-induced neuronal loss, demonstrating that SCFA stimulate enteric neurogenesis in vivo.
Our results demonstrate a role for the gut microbiota in regulating the structure and function of the GI tract in a sex-independent manner. Moreover, the microbiota is essential for the maintenance of ENS integrity, by regulating enteric neuronal survival and promoting neurogenesis. Molecular determinants of the microbiota, LPS and SCFA, regulate enteric neuronal survival, while SCFA also stimulates neurogenesis. Our data reveal new insights into the role of the gut microbiota that could lead to therapeutic developments for the treatment of enteric neuropathies. Video abstract.
The gut microbiome consists of a multi-kingdom microbial community. Whilst the role of bacteria as causal contributors governing host physiological development is well established, the role of fungi ...remains to be determined. Here, we use germ-free mice colonized with defined species of bacteria, fungi, or both to differentiate the causal role of fungi on microbiome assembly, immune development, susceptibility to colitis, and airway inflammation. Fungal colonization promotes major shifts in bacterial microbiome ecology, and has an independent effect on innate and adaptive immune development in young mice. While exclusive fungal colonization is insufficient to elicit overt dextran sulfate sodium-induced colitis, bacterial and fungal co-colonization increase colonic inflammation. Ovalbumin-induced airway inflammation reveals that bacterial, but not fungal colonization is necessary to decrease airway inflammation, yet fungi selectively promotes macrophage infiltration in the airway. Together, our findings demonstrate a causal role for fungi in microbial ecology and host immune functionality, and therefore prompt the inclusion of fungi in therapeutic approaches aimed at modulating early life microbiomes.
In the functional foods market, the products targeting health and mental well- being have prompted the food industry to increase research and development of these new foods. Despite the uncertainties ...of existing regulations, outlining the context of a rapidly expanding market in main countries. This paper provides an overview of the current situation of the global market of functional foods. The objective of this analysis is to determine whether, and in what way, the field of functional foods can actually be an opportunity both for food companies, in terms of economic benefit, and for consumers, as an opportunity healthy products. Keywords: consumers, consumption trends, functional foods, health claims, market
Dexamethasone (DEX)-induced arterial stiffness is an important side-effect, associated with hypertension and future cardiovascular events, which can be counteracted by exercise training. The aim of ...this study was to evaluate the mechanisms induced by combined training to attenuate arterial stiffness and hypertension in spontaneously hypertensive rats treated or not with dexamethasone. Spontaneously hypertensive rats (SHR) underwent combined training for 74 days and were treated with dexamethasone (50 µg/kg
s. c
.) or saline solution during the last 14 days. Wistar rats were used as controls. Echocardiographic parameters, blood pressure (BP) and pulse wave velocity (PWV), as well as histological analyses of the heart and aorta, carotid and femoral arteries were performed. At the beginning, SHR had higher BP and PWV compared with Wistar rats. After 60 days, while BP increased in sedentary SHR, combined exercise training decreased BP and PWV. After 74d, the higher BP and PWV of sedentary SHR was accompanied by autonomic imbalance to the heart, cardiac remodeling, and higher arterial collagen deposition. DEX treatment did not change these parameters. On the other hand, trained SHR had reduced BP and PWV, which was associated with better autonomic balance to the heart, reduced myocardial collagen deposition, as well as lower arterial collagen deposition. The results of this study suggest that combined training, through the reduction of aortic collagen deposition, is an important strategy to reduce arterial stiffness in spontaneously hypertensive rats, and these lower responses were maintained regardless of dexamethasone treatment.
Background and Purpose
The pathogenesis of the inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), involves aberrant interactions between a genetically ...susceptible individual, their microbiota and environmental factors. Alterations in xenobiotic receptor expression and function are associated with increased risk for IBD. Here, we have assessed the role of the constitutive androstane receptor (CAR), a xenobiotic receptor closely related to the pregnane X receptor, in the regulation of intestinal mucosal homeostasis.
Experimental Approach
CAR expression was assessed in intestinal mucosal biopsies obtained from CD and UC patients, and in C57/Bl6 mice exposed to dextran sulphate sodium (DSS; 3.5% w/v in drinking water) to evoke intestinal inflammation and tissue damage. CAR‐deficient mice were exposed to DSS and mucosal healing assessed. Modulation of wound healing by CAR was assessed in vitro. The therapeutic potential of CAR activation was evaluated, using 3,3′,5,5′‐tetrachloro‐1,4‐bis(pyridyloxy)benzene (TCPOBOP), a selective rodent CAR agonist.
Key Results
CAR expression was reduced in CD and UC samples, compared with expression in healthy controls. This was reproduced in our DSS studies, where CAR expression was reduced in colitic mice. CAR‐deficient mice exhibited reduced healing following DSS exposure. In vitro, CAR activation accelerated intestinal epithelial wound healing by enhancing cell migration. Lastly, treating mice with TCPOBOP, following induction of colitis, enhanced mucosal healing.
Conclusion and Implications
Our results support the notion that xenobiotic sensing is altered during intestinal inflammation, and suggest that CAR activation may prove effective in enhancing mucosal healing in patients with IBD.
Nanoparticle (NP) applications have recently gained more space in the development of many products, especially in cosmetology. The aim of the present study was to validate a single particle ...inductively coupled plasma mass spectrometry technique for the detection and quantification of gold nanoparticles (AuNPs) and gold ions (Au (i)) in different cosmetics currently marketed in Brazil. The size limit of detection for pure AuNPs was 22 nm, and a concentration limit of detection of 2.3×106 particles g−1 was achieved. The limit of detection for total gold was 0.02 µg L−1 obtained in standard mode conditions. The recovery achieved was 98% for dissolved Au and 109% for AuNPs; the relative standard deviation was <5%. This validated method was applied to cosmetic products (n = 10) from different national and international industrial producers. Most cosmetics analysed contained quantifiable amounts of dissolved gold (< 0.005-2.1 µg g−1) and only four contained quantifiable amounts AuNPs the variability of the results detected (< LOD – 9.3 × 108 particles g−1). The products that contained the greatest amount of these metallic NPs were the artisanal products. The results demonstrate the importance of adequate quality control for cosmetics to ensure consumer safety
DETECTION AND QUANTIFICATION OF SILVER NANOPARTICLES BY spICP-MS. The growing interest in nanotechnology has led to an increase in the production and application of nanoparticles worldwide. Due to ...the unique functional properties of nanoparticles, these materials are being used by many industries, including the agricultural and food sectors. Among the commercially available nanomaterials, it is possible to highlight those produced with silver nanoparticles. One of the most promising techniques for the analysis of metallic nanoparticles is the Inductively coupled plasma mass spectrometry (ICP-MS) performed in single particle mode (spICP-MS). However, the use of the technique in the detection and measurement of nanoparticles requires that the equipment be operated differently than when used to analyze dissolved metal solutions. Thus, this article presents the use of the spICP-MS technique for the measurement and quantification of nanoparticles, as well as their validation. The method proved to be adequate for the purpose, presenting a satisfactory result for the selectivity test and recovery of 83.7 (40 nm) and 77.6% (80 nm). The detection limits, determined for the most frequent size, dissolved silver concentration and particle concentration, were 17.5 nm, 0.736 ng mL-1,146 particles mL-1, respectively. Thus, the results obtained indicated the possibility of using the technique to determine the size and concentration of silver nanoparticles.
TNBS-induced colitis is an experimental immunopathology in rats that shares many features with human inflammatory bowel diseases. Copaiba oleoresin is extracted from plants of the genus Copaifera and ...is shown to reduce inflammation.
The aim of this study was to investigate the action of copaiba oil (C. reticulata Ducke) on inflammation and oxidative status in the distal colon of colitic rats.
Acute and subchronic colitis were induced in Wistar rats by an intracolonic enema with 2,4,6-trinitrobenzenesulfonic acid (TNBS). The colonic morphology was assessed by histological analysis and the oxidative stress parameters were measured in the intestinal homogenate. The liver damage markers were measured in the plasma. Control and colitic rats were orally treated either with one single dose (acute colitis) of copaiba oil (1.15 g Kg-1) or once a day during seven days (subchronic colitis).
The intestinal morphology was severely modified by acute and subchronic colitis, as indicated by the intramural infiltration of polymorphonuclear cells and the increased thickness of all colon layers. The levels of TBARS, protein carbonyl groups and reactive oxygen species (ROS) were increased in the intestine of colitic rats. Copaiba oil did not attenuate the inflammatory damage in acute and subchronic colitis, but it decreased the activity of myeloperoxidase, leukocyte infiltration and oxidative stress in the colon. The level of plasma bilirubin and the activity of alkaline phosphatase were both increased in treated healthy and colitic rats.
Copaiba oil decreased oxidative stress and inflammation but did not prevent intestinal damage in the colon of colitic rats. The alterations of plasma markers of hepatic damage caused by the oil seem to be associated to its harmful action on the liver.
Pulse wave velocity (PWV) has become a gold standard index to quantify the stiffness of the aorta and is a predictor of cardiovascular events. A recent paper compared the pOpmètreⓇ, a device for ...measuring the finger-toe PWV, with other techniques and demonstrated its accuracy and validity. However, human devices do not allow the advancement of our knowledge on conditioning mechanisms. Based on its human validation, a new device, pOpetⓇ 1.0 system was designed for estimation of PWV in small animals and this present study aimed to standardize the pOpetⓇ 1.0 for estimation of arterial stiffness in rats, and to confirm its liability and stability as well as the reproducibility of assessments. Therefore several precautions were taken into consideration like as the correct position of the animal and photodiodes according to manufacturers’ suggestions. Results indicated that estimation of PWV through the new pOpetⓇ 1.0 device exhibits good internal consistency, stability and objectivity in all tests performed between days and evaluators. Importantly, data suggest for the first time that this new device is able to detect changes in arterial stiffness that are conditioned by age and pressure-related arterial remodeling.
• This new pOpetⓇ device is able to detect changes in vessel structure.
• This new pOpetⓇ device exhibits good internal consistency, stability and objectivity in all tests performed
• Correct position of the animal and photodiodes are crucial to obtain a very stable signal.
Display omitted
Copper is a critical enzyme cofactor in the body but also a potent cellular toxin when intracellularly unbound. Thus, there is a delicate balance of intracellular copper, maintained by a series of ...complex interactions between the metal and specific copper transport and binding proteins. The gastrointestinal (GI) tract is the primary site of copper entry into the body and there has been considerable progress in understanding the intricacies of copper metabolism in this region. The GI tract is also host to diverse bacterial populations, and their role in copper metabolism is not well understood. In this study, we compared the isotopic fractionation of copper in the GI tract of mice with intestinal microbiota significantly depleted by antibiotic treatment to that in mice not receiving such treatment. We demonstrated variability in copper isotopic composition along the length of the gut. A significant difference, ~1.0‰, in copper isotope abundances was measured in the proximal colon of antibiotic-treated mice. The changes in copper isotopic composition in the colon are accompanied by changes in copper transporters. Both CTR1, a copper importer, and ATP7A, a copper transporter across membranes, were significantly down-regulated in the colon of antibiotic-treated mice. This study demonstrated that isotope abundance measurements of metals can be used as an indicator of changes in metabolic processes in vivo. These measurements revealed a host–microbial interaction in the GI tract involved in the regulation of copper transport.
PDF
