RESUMEN
Intestinal epithelial barrier (IEB) impairment and enteric inflammation are involved in the onset of obesity and gut-related dysmotility. Dietary supplementation with natural plant extracts represents a useful strategy for the management of body weight gain and systemic inflammation associated with obesity. Here, we evaluate the efficacy of a food supplement containing the dry extract of Curcumin, Emblica and Cassia in counteracting enteric inflammation and motor abnormalities in a mouse model of obesity, induced by a high-fat diet (HFD). Male C57BL/6 mice, fed with standard diet (SD) or HFD, were treated with a natural mixture (Curcumin, Emblica and Cassia). After 8 weeks, body weight, BMI, liver and spleen weight, along with metabolic parameters and colonic motor activity were evaluated. Additionally, plasma LBP, fecal calprotectin, colonic levels of MPO and IL-1ß, as well as the expression of occludin, TLR-4, MYD88 and NF-κB were investigated. Plant-based food supplement administration (1) counteracted the increase in body weight, BMI and metabolic parameters, along with a reduction in spleen and liver weight; (2) showed strengthening effects on the IEB integrity; and (3) reduced enteric inflammation and oxidative stress, as well as ameliorated the colonic contractile dysfunctions. Natural mixture administration reduced intestinal inflammation and counteracted the intestinal motor dysfunction associated with obesity.
RESUMEN
Growing evidence highlights the relevance of microbiota-gut-brain axis in the maintenance of brain homeostasis as well as in the pathophysiology of major neurological and psychiatric disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), autism spectrum disorder (ASD) and major depressive disorder (MDD). In particular, changes in gut microbiota can promote enteric and peripheral neurogenic/inflammatory responses, which, in turn, could contribute to neuroinflammation and neurodegeneration in the central nervous system (CNS). Of note, the nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome acts as a key player in both coordinating the host physiology and shaping the peripheral and central immune/inflammatory responses in CNS diseases. In this context, there is pioneering evidence supporting the existence of a microbiota-gut-inflammasome-brain axis, in which enteric bacteria modulate, via NLRP3 signaling, inflammatory pathways that, in turn, contribute to influence brain homeostasis. The present review provides an overview of current knowledge on the role of microbiota-gut-inflammasome-brain axis in the major CNS diseases, including PD, AD, MS, ASD and MDD. In particular, though no direct and causal correlation among altered gut microbiota, NLRP3 activation and brain pathology has been demonstrated and in-depth studies are needed in this setting, our purpose was to pave the way to a novel and pioneering perspective on the pathophysiology of CNS disorders. Our intent was also to highlight and discuss whether alterations of microbiota-gut-inflammasome-brain axis support a holistic view of the pathophysiology of CNS diseases, even though each disorder displays a different clinical picture.
Asunto(s)
Encefalopatías , Microbioma Gastrointestinal , Inflamasomas , Inflamación , Trastornos Mentales , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Encefalopatías/inmunología , Encefalopatías/metabolismo , Encefalopatías/microbiología , Microbioma Gastrointestinal/inmunología , Humanos , Inflamasomas/inmunología , Inflamasomas/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/microbiología , Trastornos Mentales/inmunología , Trastornos Mentales/metabolismo , Trastornos Mentales/microbiología , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismoRESUMEN
Obesity represents one of major health problems strongly linked to other co-morbidities, such as type 2 diabetes, CVD, gastrointestinal disorders and cognitive impairment. In this context, nutritional stress, such as an excess of fat intake, promotes a systemic oxidative stress, characterised by hyperproduction of reactive oxygen species, leading to cellular alterations that include impaired energy metabolism, altered cell signalling and cell cycle control, impaired cell transport mechanisms and overall dysfunctional biological activity. Flavonoids, dietary components of plant foods, are endowed with a wide spectrum of biological activities, including antioxidant activity, and have been proposed to reduce the risk of major chronic diseases. The present review intends to highlight and critically discuss the current scientific evidence on the possible effects of flavonoids in counteracting obesity and related co-morbidities (i.e. type 2 diabetes mellitus, CVD, gastrointestinal disorders and cognitive impairment) through a decrease in oxidative stress and related inflammatory conditions.