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 and Purpose
Hypertension is associated with gut dysbiosis. Here we have evaluated the effects of the angiotensin receptor antagonist losartan on gut microbiota in spontaneously ...hypertensive rats (SHR) to assess their contribution to its antihypertensive effects.
Experimental Approach
Twenty‐week‐old Wistar Kyoto rats (WKY) and SHR were treated with losartan for 5 weeks (SHR‐losartan). Faecal microbiota transplantation (FMT) was performed from donor SHR‐losartan group to recipient untreated‐SHR. Blood pressure (BP) was measured using tail‐cuff plethysmography. Composition of the gut microbiota was assessed by amplification of the V3‐V4 region of 16S rRNA gene. T cells were analysed in gut/aorta by flow cytometry.
Key Results
Faeces from SHR showed gut dysbiosis, characterised by higher Firmicutes/Bacteroidetes ratios, lower acetate‐ and higher lactate‐producing bacteria, and lower levels of strict anaerobic bacteria, effects which were restored to normal by losartan. Improvement of gut dysbiosis was linked to higher colonic integrity and lower sympathetic drive in the gut. In contrast, hydralazine reduced BP, but it neither restored gut dysbiosis nor colonic integrity. FMT from SHR‐losartan to SHR reduced BP, improved the aortic endothelium‐dependent relaxation to ACh, and reduced NADPH oxidase activity. These vascular changes were accompanied by both increased Treg and decreased Th17 cell populations in the vascular wall.
Conclusion and Implications
In SHR, losartan treatment reduced gut dysbiosis and sympathetic drive in the gut, thus improving gut integrity. The changes induced by losartan in gut microbiota contributed, in part, to protecting the vasculature and reducing BP, possibly by modulating the immune system in the gut.
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.
Obesity and its related disorders, such as diabetes and cardiovascular risk, represent an emerging global health issue. Even though genetic factors seem to be the primary actors in the development ...and progression of these diseases, dietary choices also appear to be of crucial importance. A healthy diet combined with physical activity have been shown to ameliorate glycaemic levels and insulin sensitivity, reduce body weight and the risk of chronic diseases, and contribute to an overall improvement in quality of life. Among nutrients, phytosterols have become the focus of growing attention as novel functional foods in the management of metabolic disorders. Phytosterols are natural plant compounds belonging to the triterpene family and are structurally similar to cholesterol. They are known for their cholesterol-lowering effects, anti-inflammatory and antioxidant properties, and the benefits they offer to the immune system. The present review aims to provide an overview of these bioactive compounds and their therapeutic potential in the fields of obesity and metabolic disorders, with special attention given to oxidative stress, inflammatory status, and gut dysbiosis, all common features of the aforementioned diseases.
Type 2 diabetes is a chronic metabolic disease that affects mitochondrial function. In this context, the rescue mechanisms of mitochondrial health, such as mitophagy and mitochondrial biogenesis, are ...of crucial importance. The gold standard for the treatment of type 2 diabetes is metformin, which has a beneficial impact on the mitochondrial metabolism. In this study, we set out to describe the effect of metformin treatment on mitochondrial function and mitophagy in peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients. We performed a preliminary cross-sectional observational study complying with CONSORT requirements, for which we recruited 242 subjects, divided into 101 healthy volunteers, 93 metformin-treated type 2 diabetic patients and 48 non-metformin-treated type 2 diabetic patients. Mitochondria from the type 2 diabetic patients not treated with metformin displayed more reactive oxygen species (ROS) than those from healthy or metformin-treated subjects. Protein expression of the electron transport chain (ETC) complexes was lower in PBMCs from type 2 diabetic patients without metformin treatment than in those from the other two groups. Mitophagy was altered in type 2 diabetic patients, evident in a decrease in the protein levels of PINK1 and Parkin in parallel to that of the mitochondrial biogenesis protein PGC1α, both of which effects were reversed by metformin. Analysis of AMPK phosphorylation revealed that its activation was decreased in the PBMCs of type 2 diabetic patients, an effect which was reversed, once again, by metformin. In addition, there was an increase in the serum levels of TNFα and IL-6 in type 2 diabetic patients and this was reversed with metformin treatment. These results demonstrate that metformin improves mitochondrial function, restores the levels of ETC complexes, and enhances AMPK activation and mitophagy, suggesting beneficial clinical implications in the treatment of type 2 diabetes.
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•Metformin promoted electron transport chain expression on type 2 diabetic patients.•Metformin restored mitophagy levels via PINK1 and PARKIN on type 2 diabetic patients.•Mitochondrial biogenesis was enhanced by metformin on type 2 diabetic patients.•Metformin restored AMPK activation on type 2 diabetic patients.
Type 2 diabetes (T2D) is a long-term metabolic disease characterized by progressive β-cell functional decline and insulin resistance, which increases the risk of cardiovascular complications as well ...as associated-morbidity and mortality. Evidence suggests a strong relationship between hyperglycaemia, oxidative stress and the development and progression of T2D. Indeed, a hyperglycaemic state can reduce the activity of antioxidant enzymes and increase lipid-peroxidation and protein oxidation products, as well as DNA damage. At present, metformin is the recommended first-line glucose-lowering agent in patients with T2D. Despite the vast clinical experience gained over several decades of use, several mechanisms of action of metformin have yet to be fully elucidated. This review provides an overview of the existing literature concerning the complicated interplay between oxidative stress and T2D and the molecular mechanisms underlying the redox-related mechanisms of action of metformin, which include (but are not limited to) interaction with AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms, inhibition of gluconeogenesis, and action on leukocyte-endothelium interactions.
This work addresses the role of different by-products derived from the industrial extraction of orange juice in a possible anti-inflammatory effect in mice with colitis induced by dextran sulfate ...sodium (DSS). Fresh orange residue (FOR), dry orange residue (DOR), orange liqueur (OL) and animal feed (AF), as well as commercial citrus pectin (CP), were administered to C57BL/6J mice for 15 days before starting the DSS treatment. Analysis of macroscopic parameters such as the Disease Activity Index (DAI) and the colonic weight/length ratio revealed an anti-inflammatory effect following intake of FOR, AF or CP. Moreover, q-PCR of RNA from colonic tissue indicated measurable changes in the expression of TNF-α, IL-1β, iNOS, and intercellular adhesion molecules ICAM I, as well as in intestinal barrier proteins such as MUC-3, occludin, and ZO-1. Pectin, phenolic compounds and/or Maillard reaction products formed at initial steps were identified as relevant components exerting the ascribed beneficial effects. Our findings could open up the further application of a variety of orange by-products as food supplements in the potential amelioration of inflammatory bowel diseases.
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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