Crohn’s disease and ulcerative colitis are the two most common categories of inflammatory bowel disease (IBD), which are characterized by chronic inflammation of the intestine that comprises the ...patients’ life quality and requires sustained pharmacological and surgical treatments. Since their aetiology is not completely understood, nonfully efficient drugs have been developed and those that show effectiveness are not devoid of quite important adverse effects that impair their long-term use. Therefore, many patients try with some botanical drugs, which are safe and efficient after many years of use. However, it is necessary to properly evaluate these therapies to consider a new strategy for human IBD. In this report we have reviewed the main botanical drugs that have been assessed in clinical trials in human IBD and the mechanisms and the active compounds proposed for their beneficial effects.
Background
Amoxicillin (AX) is nowadays the β‐lactam that more frequently induces immediate allergic reactions. Nevertheless, diagnosis of AX allergy is occasionally challenging due to risky in vivo ...tests and non‐optimal sensitivity of in vitro tests. AX requires protein haptenation to form multivalent conjugates with increased size to be immunogenic. Knowing adduct structural features for promoting effector cell activation would help to improve in vitro tests. We aimed to identify the optimal structural requirement in specific cellular degranulation to AX using well‐precised nanoarchitectures of different lengths.
Method
We constructed eight Bidendron Antigens (BiAns) based on polyethylene glycol (PEG) linkers of different lengths (600–12,000 Da), end‐coupled with polyamidoamine dendrons that were terminally multi‐functionalized with amoxicilloyl (AXO). In vitro IgE recognition was studied by competitive radioallergosorbent test (RAST) and antibody–nanoarchitecture complexes by transmission electron microscopy (TEM). Their allergenic activity was evaluated using bone marrow‐derived mast cells (MCs) passively sensitized with mouse monoclonal IgE against AX and humanized RBL‐2H3 cells sensitized with polyclonal antibodies from sera of AX‐allergic patients.
Results
All BiAns were recognized by AX‐sIgE. Dose‐dependent activation responses were observed in both cellular assays, only with longer structures, containing spacers in the range of PEG 6000–12,000 Da. Consistently, greater proportion of immunocomplexes and number of antibodies per complex for longer BiAns were visualized by TEM.
Conclusions
BiAns are valuable platforms to study the mechanism of effector cell activation. These nanomolecular tools have demonstrated the importance of the adduct size to promote effector cell activation in AX allergy, which will impact for improving in vitro diagnostics.
The use of BiAns demonstrates the importance of adduct size and distance between determinants to promote effector cell activation in AX allergy. Optimal effector cell activation is showed with the biggest BiAns, which involves a greater number of immunocomplex and antibodies. BiAns are versatile nanoplatforms that can be applied to different allergies, valuable for improving in vitro allergy tests. Abbreviations: AX, amoxicillin; AXO, amoxicilloyl; BiAn, bidendron antigen; MoAb, monoclonal antibody; RBL, rat basophilic leukemia cell
Scope
Capsicum annuum L. cv Senise is a sweet pepper containing health promoting compounds that can be modified by ripening and drying. This study focuses on finding the peppers with the best ...antioxidant properties, which are evaluated on an experimental model of obesity.
Methods and Results
Phytochemical profile and antioxidant activity are evaluated on several peppers obtained from the same cultivar at different ripening stages. Red sweet peppers show the highest content in polyphenols, β‐carotene, lycopene, and capsinoids, and demonstrate the best antioxidant activity in vitro. Mice fed a high fat diet are orally treated with an extract from these peppers (Capsicum annuum extract CAE) (1, 10, and 25 mg/kg/day). It promotes weight loss and improves plasma markers related to glucose and lipid metabolisms. CAE also ameliorates obesity‐associated systemic inflammation reducing the expression of pro‐inflammatory cytokines in adipose and hepatic tissues and improving the expression of different markers involved in the gut epithelial barrier function. These effects are associated with a modulation of the intestinal microbiome, which appears altered.
Conclusions
The extract can be considered a new potential approach for the treatment of obesity, complementary to dietary restrictions.
This study focuses on finding the peppers with the best antioxidant properties, which are evaluated on an experimental model of obesity. The extract could be considered a new potential approach for the treatment of obesity, complementary to dietary restrictions.
•C-glycosyl flavonoids were identified and quantified in Passiflora edulis by UPLC–QToF-MS.•P. edulis peel effect was evaluated in the DSS model of mice colitis.•P. edulis peel intake decreased ...inflammatory markers and histological damage.•P. edulis peel improved intestinal barrier function.
Low dietary fibre intake has been associated with inflammatory bowel disease incidence. Passiflora edulis peel is considered to be a functional food because of its level of dietary fibre and polyphenols. Female C57BL/6J mice were assigned to three different groups: healthy, dextran sodium sulphate (DSS)-control, and Passiflora edulis treated. Treatment with P. edulis peel flour (8 mg/mL in the drinking water) started 2 weeks before colitis induction, which was performed by adding DSS in the drinking water (3%) for 5 days. P. edulis peel intake exerted an intestinal anti-inflammatory effect and attenuated the colonic damage caused by the DSS, as shown by the reduced disease activity index (DAI) values and after histological evaluation. Biochemical and molecular analyses revealed reduced expression of pro-inflammatory cytokine expression and enhanced intestinal protective barrier. Besides these effects, increases in short-chain fatty acid formation were observed, thus supporting a prebiotic effect.
probiotics contained in dietary supplements or functional foods are well-known for their beneficial properties exerted on host health and diverse pathological situations. Their capacity to improve ...inflammatory bowel disease (IBD) and regulate the immune system is especially remarkable. Although bacteria-host interactions have been thought to occur directly, the key role that extracellular vesicles (EVs) derived from probiotics play on this point is being unveiled. EVs are lipid bilayer-enclosed particles that carry a wide range of cargo compounds and act in different signalling pathways. Notably, these EVs have been recently proposed as a safe alternative to the utilisation of live bacteria since they can avoid the possible risks that probiotics may entail in vulnerable cases such as immunocompromised patients. Therefore, this review aims to give an updated overview of the existing knowledge about EVs from different
strains, their mechanisms and effects in host health and different pathological conditions. All of the information collected suggests that EVs could be considered as potential tools for the development of future novel therapeutic approaches.
The beneficial effects of probiotics on immune-based pathologies such as inflammatory bowel disease (IBD) have been well reported. However, their exact mechanisms have not been fully elucidated. Few ...studies have focused on the impact of probiotics on the composition of the colonic microbiota. The aim of the present study was to correlate the intestinal anti-inflammatory activity of the probiotic
Nissle 1917 (EcN) in the dextran sodium sulfate (DSS) model of mouse colitis with the changes induced in colonic microbiota populations. EcN prevented the DSS-induced colonic damage, as evidenced by lower disease activity index (DAI) values and colonic weight/length ratio, when compared with untreated control mice. The beneficial effects were confirmed biochemically, since the probiotic treatment improved the colonic expression of different cytokines and proteins involved in epithelial integrity. In addition, it restored the expression of different micro-RNAs (miR-143, miR-150, miR-155, miR-223, and miR-375) involved in the inflammatory response that occurs in colitic mice. Finally, the characterization of the colonic microbiota by pyrosequencing showed that the probiotic administration was able to counteract the dysbiosis associated with the intestinal inflammatory process. This effect was evidenced by an increase in bacterial diversity in comparison with untreated colitic mice. The intestinal anti-inflammatory effects of the probiotic EcN were associated with an amelioration of the altered gut microbiome in mouse experimental colitis, especially when considering bacterial diversity, which is reduced in these intestinal conditions. Moreover, this probiotic has shown an ability to modulate expression levels of miRNAs and different mediators of the immune response involved in gut inflammation. This modulation could also be of great interest to understand the mechanism of action of this probiotic in the treatment of IBD.
Abstract
Aim
High blood pressure (BP) is associated with gut microbiota dysbiosis. The aim of this study was to investigate whether changes in gut microbiota induced by exchanging the gut microbiota ...between spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) alter the gut‐immune system interaction inducing changes in vascular function and BP.
Methods
Twenty‐week‐old recipient WKY and SHR were orally gavaged with donor faecal contents from WKY or SHR. In additional experiments, we used a design to determine whether blockade of B7‐dependent costimulation with CTLA4‐Ig or blockade of IL‐17 with IL‐17‐neutralizing antibody could prevent hypertension caused by faecal microbiota transplantation (FMT) from SHR to WKY.
Results
Correlation analyses identified the bacterial abundance of
Turicibacter
and
S24‐7_g
that, respectively, positively and negatively correlated with systolic BP. FMT from WKY rats to SHR rats reduced basal systolic BP, restored the imbalance between Th17/Treg in mesenteric lymph nodes (MLNs) and aorta, and improved endothelial dysfunction and vascular oxidative status found in SHR transplanted with SHR faeces. FMT from SHR to WKY increased CD80 and CD86 mRNA levels and T cells activation in MLNs, circulating T cells, aortic T cell infiltration, impaired endothelial function and increased basal SBP. These effects were abolished by blockade of B7‐dependent costimulation with CTLA4‐Ig. IL‐17a neutralizing antibody reduced SBP and improved endothelial dysfunction induced by FMT from SHR to WKY.
Conclusion
Gut microbiota is an important factor involved in the control of BP, as a consequence of its effect in T‐cell activation in gut immune system and vascular T‐cells accumulation.
Purpose
Probiotics have been shown to exert beneficial effects in IBD although their exact mechanisms are not completely understood. The aim of the present study was to assess the intestinal ...anti-inflammatory activity of different probiotics (
Lactobacillus fermentum
CECT5716,
Lactobacillus salivarius
CECT5713,
Escherichia coli
Nissle 1917,
Saccharomyces boulardii
CNCMI-745 in the dinitrobenzene sulfonic acid (DNBS) model of mouse colitis and correlate it with the modifications of the gut microbiota and the immune response, focusing on miRNA expression.
Methods
The probiotics were daily administered orally for 25 days. On day 19 colitis was induced by rectal installation of DNBS. At the end of the treatment, mice were sacrificed and the colonic damage was assessed biochemically by analysing the expression of different markers involved in the immune response, including miRNAs; and the colonic microbiota by pyrosequencing. Probiotics properties were also evaluated in vitro in different immune cell types (CMT-93 intestinal epithelial cells and bone marrow-derived macrophages), where the expression of different mRNAs and miRNAs was examined.
Results
All the probiotics displayed intestinal anti-inflammatory effects but slightly different, especially regarding miRNAs expression. Likewise, the probiotics ameliorated the colitis-associated dysbiosis, although showing differences in the main bacterial groups affected.
Conclusion
Among the probiotics assayed,
Lactobacillus fermentum
CECT5716 and
Escherichia coli
Nissle 1917 appear to present the best intestinal anti-inflammatory effects, being the latter one of the few probiotics with reputed efficacy in human IBD. Therefore,
Lactobacillus fermentum
CECT5716 could be considered as a complementary nutritional strategy for IBD treatment.
Scope
Obesity is characterized by a dysfunction in the adipose tissue and an inflammatory subclinical state leading to insulin resistance and increased risk of cardiovascular diseases. It is also ...associated with intestinal dysbiosis that contributes to inflammation development. Lippia citriodora (LCE) contains high levels of polyphenolpropanoids and has shown promising results in obesity. The aim of this study is to investigate a well‐characterized extract of LCE in a model of metabolic syndrome in mice, focusing on its effects on metabolic tissues, endothelial dysfunction, and microbiome.
Methods
Mice are fed a high fat diet (HFD) for six weeks and treated daily with LCE (1, 10, and 25 mg kg−1). Glucose and lipid metabolism is investigated. The inflammatory state in the metabolic tissues and the intestinal microbiota composition are characterized, as well as the endothelium‐dependent vasodilator response to acetylcholine.
Results
LCE reduces fat accumulation and improves plasma glycemic and lipid profiles, as well as the inflammatory process and vascular dysfunction. Moreover, LCE lessens intestinal dysbiosis, as it reduces the Firmicutes/Bacteroidetes ratio and increases Akkermansia abundance in comparison with untreated HFD mice.
Conclusion
The antiobesity therapeutic properties of LCE are most probably mediated by the synergic effects of its bioactive compounds.
The aim of this study is the evaluation of Lippia Citriodora extract (LCE) treatment on diet‐induced obesity in mice. LCE administration ameliorates induced obesity, enhancing the inflammatory status and the vascular functionality. Furthermore, it is the first time that LCE treatment is shown to modulate the gut microbiota. These findings support the use of LCE as a new functional food in metabolic syndrome.
Aim
Disruption of the intestinal mucosal tolerance, that is, the immunological unresponsiveness to innocuous food antigens and the commensal microbiota, in the colon is associated with several ...chronic diseases including inflammatory bowel disease (IBD). Understanding the mechanisms responsible for intestinal mucosal tolerance has potential translational value for its therapy and management. Human intestinal mesenchymal cells (iMCs) play important roles in colonic mucosal tolerance, but further studies on their tissue regenerative and immunomodulatory capacities are necessary in order to fully understand their function in health and disease.
Methods
In this study, we have isolated and analysed the capacity of human iMCs to promote wound healing and modulate immune responses in vitro and in vivo, using the dextran sulfate sodium (DSS)‐induced colitis model.
Results
Cultured iMCs were CD45−CD73+CD90+CD105+ and accelerated the wound closure in a normal colon mucosa (NCM) 356 human epithelial cell wound healing assay. Furthermore, iMCs blocked the LPS‐mediated induction of TNF‐α in THP‐1 macrophages and inhibited the proliferation of peripheral blood mononuclear cells, partly through the induction of indoleamine‐2,3‐dioxygenase. In DSS colitic mice, iMCs administration reduced the disease activity index and ameliorated intestinal tissue damage and permeability. Furthermore, iMCs reduced intestinal inflammation, evidenced by a decreased mRNA expression of pro‐inflammatory cytokines, reduced IL‐1β secretion by intestinal explants and inhibited colonic iNOS protein expression.
Conclusions
Our data show that human iMCs isolated from the noninflamed intestine possess tissue‐regenerative and immunomodulatory capacities that could potentially be harnessed/restored in order to reduce IBD severity.
PDF
