Scope
To compare the intestinal anti‐inflammatory effects of two probiotics Lactobacillus fermentum and Lactobacillus salivarius in mouse colitis, focusing on their impact on selected miRNAs and ...microbiota composition.
Methods and results
Male C57BL/6J mice were randomly assigned to four groups (n = 10): non‐colitic, DSS colitic and two colitic groups treated with probiotics (5 × 108 CFU/mouse/day). Both probiotics ameliorated macroscopic colonic damage. They improved the colonic expression of markers involved in the immune response, and the expression of miR‐155 and miR‐223. L. fermentum also restored miR‐150 and miR‐143 expression, also linked to the preservation of the intestinal barrier function. Besides, these beneficial effects were associated with the amelioration of the microbiota dysbiosis and a recovery of the SCFAs‐ and lactic acid‐producing bacterial populations, although only L. fermentum improved Chao richness, Pielou evenness and Shannon diversity. Moreover, L. fermentum also restored the Treg cell population in MLNs and the Th1/Th2 cytokine balance.
Conclusion
Both probiotics exerted intestinal anti‐inflammatory effects in DSS‐mouse colitis, maybe due to their ability to restore the intestinal microbiota homeostasis and modulate the immune response. L. fermentum showed a greater beneficial effect compared to L. salivarius, which makes it more interesting for future studies.
Lactobacillus fermentum and L. salivarius, exert intestinal anti‐inflammatory effects in mouse DSS colitis, maybe due to their ability to restore intestinal microbiota composition and modulate the immune response. L. fermentum improved more parameters than L. salivarius, which makes it more interesting for future studies.
Nissle 1917 (EcN) is a probiotic strain with proven efficacy in inducing and maintaining remission of ulcerative colitis. However, the microbial factors that mediate these beneficial effects are not ...fully known. Gram-negative bacteria release outer membrane vesicles (OMVs) as a direct pathway for delivering selected bacterial proteins and active compounds to the host. In fact, vesicles released by gut microbiota are emerging as key players in signaling processes in the intestinal mucosa. In the present study, the dextran sodium sulfate (DSS)-induced colitis mouse model was used to investigate the potential of EcN OMVs to ameliorate mucosal injury and inflammation in the gut. The experimental protocol involved pre-treatment with OMVs for 10 days before DSS intake, and a 5-day recovery period. Oral administration of purified EcN OMVs (5 μg/day) significantly reduced DSS-induced weight loss and ameliorated clinical symptoms and histological scores. OMVs treatment counteracted altered expression of cytokines and markers of intestinal barrier function. This study shows for the first time that EcN OMVs can mediate the anti-inflammatory and barrier protection effects previously reported for this probiotic in experimental colitis. Remarkably, translation of probiotics to human healthcare requires knowledge of the molecular mechanisms involved in probiotic-host interactions. Thus, OMVs, as a non-replicative bacterial form, could be explored as a new probiotic-derived therapeutic approach, with even lower risk of adverse events than probiotic administration.
Scope
Propyl‐propane thiosulfonate (PTSO) is a component isolated from garlic (Allium sativum) with antioxidant, anti‐inflammatory, immunomodulatory, and antimicrobial properties. In consequence, ...PTSO can be a potential candidate for the treatment of inflammatory bowel diseases.
Methods and results
The anti‐inflammatory effects of PTSO are studied in two mice models of colitis: 2,4‐dinitrobenzene sulfonic acid (DNBS) (PTSO doses: 0.01–10 mg kg–1) and dextran sodium sulfate (DSS) (PTSO doses: 0.01–0.1 mg kg–1). The immunomodulatory effects of PTSO (0.1–25 µm) are also shown in vitro in Caco‐2 and THP‐1 cells, reducing the production of pro‐inflammatory mediators and downregulating mitogen‐activated protein kinases (MAPKs) signaling pathways. This compound displays beneficial effects in both models of mouse colitis by reducing the expression of different pro‐inflammatory mediators and improving the intestinal epithelial barrier integrity. Moreover, PTSO ameliorates the altered gut microbiota composition observed in DSS colitic mice.
Conclusion
PTSO exerts intestinal anti‐inflammatory activity in experimental colitis in mice. This anti‐inflammatory activity can be associated with the immunomodulatory properties of PTSO through the regulation of the activity of cells involved in the inflammatory response. Furthermore, PTSO is able to restore the intestinal epithelial barrier function and to ameliorate the intestinal microbiota homeostasis, thus supporting its future development in human IBD.
Propyl‐propane thiosulfonate (PTSO) shows intestinal anti‐inflammatory properties in two experimental models of mouse colitis, 2,4‐dinitrobenzene sulfonic acid and dextran sodium sulfate, which are associated with reduced expression of pro‐inflammatory mediators, improvement of intestinal epithelial barrier integrity, and amelioration of altered gut microbiota composition. In vitro assays in Caco‐2 and THP‐1 cells reveal that PTSO reduced the production of pro‐inflammatory mediators and downregulated mitogen‐activated protein kinases signaling pathways.
Scope
The aim is to analyze whether the probiotic Lactobacillus fermentum CECT5716 (LC40) can prevent endothelial dysfunction and hypertension induced by tacrolimus in mice.
Methods and results
...Tacrolimus increases systolic blood pressure (SBP) and impairs endothelium‐dependent relaxation to acetylcholine and these effects are partially prevented by LC40. Endothelial dysfunction induced by tacrolimus is related to both increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) and uncoupled endothelial nitric oxide synthase (eNOS)‐driven superoxide production and Rho‐kinase‐mediated eNOS inhibition. LC40 treatment prevents all the aortic changes induced by tacrolimus. LC40 restores the imbalance between T‐helper 17 (Th17)/regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and the spleen. Tacrolimus‐induced gut dysbiosis, that is, it decreases microbial diversity, increases the Firmicutes/Bacteroidetes (F/B) ratio and decreases acetate‐ and butyrate‐producing bacteria, and these effects are prevented by LC40. Fecal microbiota transplantation (FMT) from LC40‐treated mice to control mice prevents the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus.
Conclusion
LC40 treatment prevents hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects are associated with a reduction in vascular oxidative stress, mainly through NOX2 downregulation and prevention of eNOS uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes.
Lactobacillus fermentum CECT5716 (LC40) treatment prevented hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects were associated with a reduction in vascular oxidative stress, mainly through NOX2 downregulation and prevention of eNOS uncoupling, and inflammation possibly because of decreased T‐helper 17 cells (Th17) and increased regulatory T (Treg) cells polarization in mesenteric lymph nodes.
Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the intestine that compromises the patients' life quality and requires sustained pharmacological and surgical treatments. ...Since their etiology is not completely understood, non-fully-efficient drugs have been developed and those that have shown effectiveness are not devoid of quite important adverse effects that impair their long-term use. In this regard, a growing body of evidence confirms the health benefits of flavonoids. Flavonoids are compounds with low molecular weight that are widely distributed throughout the vegetable kingdom, including in edible plants. They may be of great utility in conditions of acute or chronic intestinal inflammation through different mechanisms including protection against oxidative stress, and preservation of epithelial barrier function and immunomodulatory properties in the gut. In this review we have revised the main flavonoid classes that have been assessed in different experimental models of colitis as well as the proposed mechanisms that support 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.
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.
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.
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