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.
Patients with inflammatory bowel disease (IBD) have a higher risk of developing colitis-associated colorectal cancer (CAC) with poor prognosis. IBD etiology remains undefined but involves ...environmental factors, genetic predisposition, microbiota imbalance (dysbiosis) and mucosal immune defects. Mesenchymal stromal cell (MSC) injections have shown good efficacy in reducing intestinal inflammation in animal and human studies. However, their effect on tumor growth in CAC and their capacity to restore gut dysbiosis are not clear.
The outcome of systemic administrations of in vitro expanded human intestinal MSCs (iMSCs) on tumor growth in vivo was evaluated using the AOM/DSS model of CAC in C57BL/6J mice. Innate and adaptive immune responses in blood, mesenteric lymph nodes (MLNs) and colonic tissue were analyzed by flow cytometry. Intestinal microbiota composition was evaluated by 16S rRNA amplicon sequencing.
iMSCs significantly inhibited colitis and intestinal tumor development, reducing IL-6 and COX-2 expression, and IL-6/STAT3 and PI3K/Akt signaling. iMSCs decreased colonic immune cell infiltration, and partly restored intestinal monocyte homing and differentiation. iMSC administration increased the numbers of Tregs and IFN-γ+CD8+ T cells in the MLNs while decreasing the IL-4+Th2 response. It also ameliorated intestinal dysbiosis in CAC mice, increasing diversity and Bacillota/Bacteroidota ratio, as well as Akkermansia abundance, while reducing Alistipes and Turicibacter, genera associated with inflammation.
Administration of iMSCs protects against CAC, ameliorating colitis and partially reverting intestinal dysbiosis, supporting the use of MSCs for the treatment of IBD.
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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.
Melatonin has shown beneficial effects on obesity, both in humans and experimental models, via regulating the altered circadian rhythm and thus ameliorating the gut dysbiosis associated with this ...metabolic condition. However, its clinical use is limited, mostly due to its short half-life. Agomelatine is an agonist of the melatonin receptors that could be used to manage obesity and offer a better profile than melatonin.
Male C57BL/6 mice were fed a high fat diet and orally treated for five weeks with agomelatine, or melatonin or metformin, used as control drugs. Metabolic profile, inflammatory status, vascular dysfunction and intestinal microbiota composition were assessed.
Agomelatine lessened body weight gain, enhanced glucose and lipid metabolisms, and improved insulin resistance. It also reduced the obesity-associated inflammatory status and endothelial dysfunction, probably linked to its effect on gut dysbiosis, consisting of the restoration of bacterial populations with key functions, such as short chain fatty acid production.
Agomelatine can be considered as a novel therapeutic tool for the management of human obesity and its associated comorbidities.
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Background: Propyl propane thiosulfonate (PTSO) is an organosulfur compound from Allium spp. that has shown interesting antimicrobial properties and immunomodulatory effects in different experimental ...models. In this sense, our aim was to evaluate its effect on an experimental model of obesity, focusing on inflammatory and metabolic markers and the gut microbiota. Methods and results: Mice were fed a high-fat diet and orally treated with different doses of PTSO (0.1, 0.5 and 1 mg/kg/day) for 5 weeks. PTSO lessened the weight gain and improved the plasma markers associated with glucose and lipid metabolisms. PTSO also attenuated obesity-associated systemic inflammation, reducing the immune cell infiltration and, thus, the expression of pro-inflammatory cytokines in adipose and hepatic tissues (Il-1ẞ, Il-6, Tnf-α, Mcp-1, Jnk-1, Jnk-2, Leptin, Leptin R, Adiponectin, Ampk, Ppar-α, Ppar-γ, Glut-4 and Tlr-4) and improving the expression of different key elements for gut barrier integrity (Muc-2, Muc-3, Occludin, Zo-1 and Tff-3). Additionally, these effects were connected to a regulation of the gut microbiome, which was altered by the high-fat diet. Conclusion: Allium-derived PTSO can be considered a potential new tool for the treatment of metabolic syndrome.
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.
and Purpose: Colorectal cancer (CRC) is one of the cancers with the highest incidence in which APC gene mutations occur in almost 80% of patients. This mutation leads to β-catenin aberrant ...accumulation and an uncontrolled proliferation. Apoptosis evasion, changes in the immune response and microbiota composition are also events that arise in CRC. Tetracyclines are drugs with proven antibiotic and immunomodulatory properties that have shown cytotoxic activity against different tumor cell lines.
The effect of tigecycline was evaluated in vitro in HCT116 cells and in vivo in a colitis-associated colorectal cancer (CAC) murine model. 5-fluorouracil was assayed as positive control in both studies.
Tigecycline showed an antiproliferative activity targeting the Wnt/β-catenin pathway and downregulating STAT3. Moreover, tigecycline induced apoptosis through extrinsic, intrinsic and endoplasmic reticulum pathways converging on an increase of CASP7 levels. Furthermore, tigecycline modulated the immune response in CAC, reducing the cancer-associated inflammation through downregulation of cytokines expression. Additionally, tigecycline favored the cytotoxic activity of cytotoxic T lymphocytes (CTLs), one of the main immune defenses against tumor cells. Lastly, the antibiotic reestablished the gut dysbiosis in CAC mice increasing the abundance of bacterial genera and species, such as Akkermansia and Parabacteroides distasonis, that act as protectors against tumor development. These findings resulted in a reduction of the number of tumors and an amelioration of the tumorigenesis process in CAC.
Tigecycline exerts a beneficial effect against CRC supporting the use of this antibiotic for the treatment of this disease.
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•Tigecycline showed an antiproliferative activity targeting the Wnt/β-catenin and STAT3 pathway.•The administration of Tigecycline ameliorated the tumorigenesis process and induced apoptosis.•Tigecycline reduced the cancer-associated inflammation.•Tigecycline treatment positively impacted gut dysbiosis in CAC mice.•Tigecycline would constitute a potential new tool for the management of CRC.
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.
L., commonly known as scarlet eggplant (Solanaceae family) is one of the most traditionally cultivated vegetables in Basilicata, a southern region of Italy. Although multiple uses have been given to ...this vegetable, data about its anti-obesogenic activity are still limited.
This study focuses on testing two different extracts obtained either from the peel or from the whole fruit of the Lucanian
Their ability to inhibit certain enzymatic activities was tested
and then, the one that showed the better outcomes was tested on an experimental model of High-Fat Diet (HFD) induced obesity.
Spectrophotometric assays demonstrated that the peel extract possessed the highest ability to inhibit the selected enzymatic activities and so, its phytochemical profile was obtained through LC-MS chromatography. The oral administration of this extract (25 mg/kg) to HFD-fed mice reduced body weight gain and improved glucose and lipid metabolism. Similarly, the extract ameliorated the obesity-induced inflammatory status by reducing the expression of pro-inflammatory cytokines in both adipose and hepatic tissues. Interestingly, these effects were associated with the improvement of vascular dysfunction.
Lucanian
extract may represent a new strategic approach for managing obesity and its associated diseases.
Limosilactobacillus fermentum CECT5716, a probiotic strain isolated from human milk, has reported beneficial effects on different gastrointestinal disorders. Moreover, it has shown its ability to ...restore altered immune responses, in association with microbiome modulation in different pathological conditions. Therefore, our aim was to assess the effects of a Limosilacbacillus fermentum CECT5716 in a rat experimental model of irritable bowel syndrome (IBS) that resembles human IBS. The experimental IBS was induced by deoxycholic acid (DCA) in rats and then, Limosilactobacillus fermentum CECT5716 (109 CFU/day/rat) was administered. Behavioral studies, hyperalgesia and intestinal hypersensitivity determinations were performed and the impact of the probiotic on the inflammatory and intestinal barrier integrity was evaluated. Additionally, the gut microbiota composition was analyzed. Limosilactobacillus fermentum CECT5716 attenuated the anxiety-like behavior as well as the visceral hypersensitivity and referred pain. Moreover, this probiotic ameliorated the gut inflammatory status, re-establishing the altered intestinal permeability, reducing the mast cell degranulation and re-establishing the gut dysbiosis in experimental IBS. Therefore, our results suggest a potential use of Limosilactobacillus fermentum CECT5716 in clinical practice for the management of IBS patients.
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