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Green tea extract prevents obesity in male mice by alleviating gut dysbiosis in association with improved intestinal barrier function that limits endotoxin translocation and adipose inflammation

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Abstract

Gut-derived endotoxin translocation provokes obesity by inducing TLR4/NFκB inflammation. We hypothesized that catechin-rich green tea extract (GTE) would protect against obesity-associated TLR4/NFκB inflammation by alleviating gut dysbiosis and limiting endotoxin translocation. Male C57BL/6J mice were fed a low-fat (LF) or high-fat (HF) diet containing 0% or 2% GTE for 8-wk. At wk 7, fluorescein isothiocyanate (FITC)-dextran was administered by oral gavage before assessing its serum concentrations as a gut permeability marker. HF-feeding increased (P<0.05) adipose mass and adipose expression of genes involved in TLR4/NFκB-dependent inflammation and macrophage activation. GTE attenuated HF-induced obesity and pro-inflammatory gene expression. GTE in HF mice decreased serum FITC-dextran, and attenuated portal vein and circulating endotoxin concentrations. GTE in HF mice also prevented HF-induced decreases in the expression of intestinal tight junction proteins (TJPs) and hypoxia inducible factor-1α while preventing increases in TLR4/NFκB-dependent inflammatory genes. Gut microbial diversity was increased, and the Firmicutes:Bacteroidetes ratio was decreased, in HF mice fed GTE compared with HF controls. GTE in LF mice did not attenuate adiposity but decreased endotoxin and favorably altered several gut bacterial populations. Serum FITC-dextran was correlated with portal vein endotoxin (P<0.001; rP = 0.66) and inversely correlated with colonic mRNA levels of TJPs (P<0.05; rP = -0.38 to -0.48). Colonic TJPs mRNA were inversely correlated with portal endotoxin (P<0.05; rP = -0.33 to -0.39). These data suggest that GTE protects against diet-induced obesity consistent with a mechanism involving the gut-adipose axis that limits endotoxin translocation and consequent adipose TLR4/NFκB inflammation by improving gut barrier function.

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... EC-rich diet supplementation helps improve intestinal permeability because EC inhibits NADPH and NF-κB, and NF-κB and its induced TNF-α lead to downregulation of ZO-1 [142,143]. Moreover, catechin-rich green tea extract (GTE) is related to the hypoxia-inducible factor (HIF)-1α in downregulating TJ-related proteins induced by HFD [144]. Indeed, HIF-1α is involved in the regulation of TJ-related protein expression [145]. ...
... Indeed, HIF-1α is involved in the regulation of TJ-related protein expression [145]. Dey et al. found a positive correlation between HIF-1α and claudin-1 expressions, but the regulation of TJ by GTE via HIF-1α remains unknown [144]. ...
... Intestinal microorganisms are in direct contact with catechins, which might affect their biological activities. For example, green tea rich in catechins attenuates the function of microorganisms to metabolize amino and nucleotide sugars, providing the skeleton for LPS synthesis and helping reduce LPS-induced damage to the body and insulin resistance [144]. ...
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Catechins are key functional components in tea and have many health benefits, including relieving diabetes. Glucose is necessary for maintaining life. However, when the glucose in the serum exceeds the threshold, it will lead to hyperglycemia. Hyperglycemia is mainly caused by insufficient insulin secretion or insulin resistance. Persistent hyperglycemia can cause various disorders, including retinopathy, nephropathy, neurodegenerative diseases, cardiovascular disease, and diabetes. In this paper, we summarize the research on the underlying mechanisms of catechins in regulating diabetes and elaborate on the mechanisms of catechins in alleviating hyperglycemia by improving insulin resistance, alleviating oxidative stress, regulating mitochondrial function, alleviating endoplasmic reticulum stress, producing anti-inflammatory effects, reducing blood sugar source, and regulating intestinal function. This review will provide scientific direction for future research on catechin alleviating diabetes.
... epigallocatechin-3-gallate (EGCG) and catechin) dietary component. From previous study, green tea has been shown antioxidant and anti-inflammatory properties which were associated with health benefits in treating obesity, diabetes, and cancers among others (Bruno, Dugan, Smyth, DiNatale, & Koo, 2008;Dey et al., 2019;Hodges, Sasaki, & Bruno, 2020;Park et al., 2011;Park et al., 2012;Perez-Burillo et al., 2021). Polyphenols in green tea could be metabolized by gut bacteria and phenolic compounds have shown inhibitory effects on some bacteria like Helicobacter pylori and Clostridium perfringens (Liu, Bruins, Ni, & Vincken, 2018). ...
... The application of HCM has been demonstrated in previous study (Xu et al., 2020). In this study, we utilized the concentration of 2 % (w:w) GTE which is consistent with the concentration used in previous in vivo study (Dey et al., 2020;Dey et al., 2019). Our results further suggested that GTE treatment significantly regulated gut microbiota from adults with MetS at genus level in the HCM system. ...
... In addition, our large-scale metabolomics analysis based on endogenous microbial metabolites suggested that many important microbial metabolic pathways were significantly regulated after GTE treatment in ascending, transverse, and descending colons. This result showed consistency with our previous studies (Dey et al., 2019;Xu et al., 2020) that GTE supplementation could impact LPS biosynthesis and purine metabolism in gut microorganisms. Specifically, in our study, we found significant increase in microbial production of glutamine, guanosine, adenosine, and adenine involved in purine metabolism. ...
Article
Background Metabolic syndrome (MetS) is a common metatoblic disorder that leads to various adverse health outcomes such as diabetes and cardiovascular diseases (CVDs). Recent studies suggested that MetS associated gut dysbiosis could exacerbate MetS related diseases. Green tea, a popular beverage rich in polyphenols, has showed antioxidant and anti-inflammatory effects in treating MetS through gut modulation. Objectives This study aimed to understand the impact of green tea extract (GTE) on the composition and metabolism of gut microbiota from people with MetS. Methods We utilized an in-vitro human colonic model (HCM) to specifically investigate the host-free interactions between GTE and gut microbiota of MetS. Fresh fecal samples donated by three adults with MetS were used as gut microbe inoculum in our HCM system. 16S ribosomal RNA sequencing and liquid-chromatography mass spectrometry (LC/MS) combined with QIIME 2, Compound Discoverer 3.1 and MetaboAnalyst 4.0 based data analyses were performed to show the regulating effects of GTE treatment on gut microbial composition and their metabolism. Results Our data suggested that GTE treatment in HCM modified composition of MetS gut microbiota at genus level and led to significant microbiota metabolic profile change. Bioinformatics analysis showed relative abundance of Escherichia and Klebsiella was commonly increased while Bacteroides, Citrobacter, and Clostridium were significantly reduced.All free fatty acids detected were significantly increased in different colon sections. Lipopolysaccharide biosynthesis, methane metabolism, pentose phosphate pathway, purine metabolism, and tyrosine metabolism were regulated by GTE in MetS gut microbiota. In addition, we identified significant associations between altered microbes and microbial metabolites. Conclusions Overall, our study revealed the impact of GTE treatment on gut microbiota composition and metabolism changes in MetS microbiota in vitro, which may provide information for further mechanistic investigation of GTE in modulating gut dysbiosis in MetS.
... Subjects with chronic metabolic diseases are often associated with lower butyrate-producing microbes, lower abundance of Akkermansia muciniphila, and increased abundance of bacteria with inflammatory potentials (e.g., E. coli) [36]. Mice fed an obesogenic diet with liver disease and insulin resistance demonstrate a significant increase in microbial metabolic functions related to amino sugar and nucleotide metabolism, energy metabolism, and lipopolysaccharide (LPS) biosynthesis [85]. Similarly patients with type 2 diabetes show enrichment of microbial pathways related to cellular sugar uptake, xenobiotic degradation, branched-chain amino acid export related to increased insulin resistance, and sulfate reduction associated with reduction of insulin sensitivity [86]. ...
... These SCFA can exert diverse beneficial effects on the host (Fig. 5). SCFA, especially butyrate has been attributed to limiting weight gain, whereas health-beneficial effects of phytochemicals could be attributed to improving butyrogenic microbes at the intestine or improving their SCFA metabolism capacity [85]. SCFA can signal through GPCR to affect a wide spectrum of processes such as secretion of insulin and ghrelin, GLP-1, peptide tyrosine tyrosine (PYY), neutrophil migration, formation of inflammasomes and induce pro-inflammatory milieu [190]. ...
... Gut-derived endotoxin translocation to the liver through portal vein due to loss of gut barrier integrity triggers TLR4/NFκB-dependent inflammatory insult at the liver and promotes NASH [29,81]. The endotoxin load in both lean and obese mice in the portal vein is significantly higher than that of normal systemic circulation [85]. Translocation of bacterial products to the systemic circulation occurs even in healthy individuals [41] that facilitates priming of gut immune system to microbial products as a preparative measure for extensive invasion of pathobionts, and also helps to develop immune tolerance towards commensal symbionts [210]. ...
Article
The role of the intestine in human health and disease has historically been neglected and was mostly attributed to digestive and absorptive functions. In the past two decades, however, discoveries related to human nutrition and intestinal host-microbe reciprocal interaction have established the essential role of intestinal health in the pathogenesis of chronic diseases and the overall wellbeing. That transfer of gut microbiota could be a means of disease phenotype transfer has revolutionized our understanding of chronic disease pathogenesis. This narrative review highlights the major concepts related to intestinal microbiota, metabolism, and metabolome (3M) that have facilitated our fundamental understanding of the association between the intestine and human health and disease. In line with increased interest of microbiota-dependent modulation of human health by dietary phytochemicals, we have also discussed the emerging concepts beyond the phytochemical bioactivities which emphasizes the integral role of microbial metabolites of parent phytochemicals at extraintestinal tissues. Finally, this review concludes with challenges and future prospects in defining the 3 M interactions and has emphasized the fact that, it takes ‘guts’ to stay healthy.
... Kaempferol present in tea leaves improves the integrity of the intestinal barrier and inhibits inflammation in the intestines by reducing the activation of the TLR4/NF-κB pathway [248]. Studies on laboratory animals and in humans have shown that catechins inhibit the growth of pathogenic bacteria, Clostridium difficile and Staphylococcus spp., and stimulate the growth of beneficial Bifidobacterium bacteria [240,[249][250][251]. They also improve the integrity of the intestinal barrier and reduce pro-inflammatory reactions, which have been demonstrated in studies on laboratory animals and in humans [240,[249][250][251]. Studies on rats with colitis showed that the EGCG present in green tea stimulates an increase in Akkermansia abundance and the production of SCFA [252]. ...
... Studies on laboratory animals and in humans have shown that catechins inhibit the growth of pathogenic bacteria, Clostridium difficile and Staphylococcus spp., and stimulate the growth of beneficial Bifidobacterium bacteria [240,[249][250][251]. They also improve the integrity of the intestinal barrier and reduce pro-inflammatory reactions, which have been demonstrated in studies on laboratory animals and in humans [240,[249][250][251]. Studies on rats with colitis showed that the EGCG present in green tea stimulates an increase in Akkermansia abundance and the production of SCFA [252]. ...
Article
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Depressive disorders can affect up to 350 million people worldwide, and in developed countries, the percentage of patients with depressive disorders may be as high as 10%. During depression, activation of pro-inflammatory pathways, mitochondrial dysfunction, increased markers of oxidative stress, and a reduction in the antioxidant effectiveness of the body are observed. It is estimated that approximately 30% of depressed patients do not respond to traditional pharmacological treatments. However, more and more attention is being paid to the influence of active ingredients in food on the course and risk of neurological disorders, including depression. The possibility of using foods containing polyphenols as an element of diet therapy in depression was analyzed in the review. The possibility of whether the consumption of products such as polyphenols could alleviate the course of depression or prevent the progression of it was also considered. Results from preclinical studies demonstrate the potential of phenolic compounds have the potential to reduce depressive behaviors by regulating factors related to oxidative stress, neuroinflammation, and modulation of the intestinal microbiota.
... Catechin-rich green tea extract (GTE) exerts antioxidant and anti-inflammatory activities that protect against obesity in rodents by reducing gut permeability that otherwise provokes endotoxemia-mediated inflammation [7][8][9]. Clinical studies support that green tea consumption alleviates dyslipidemia [10] and increases antioxidant biomarkers [11,12]. Health benefits of GTE are attributed to its parental catechins [e.g., epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC)]. ...
... From the extracted DNA (5 µg), the V4-V5 hypervariable region of the 16S rRNA gene was amplified by PCR to prepare amplicon libraries which were pair-end sequenced (2 × 300) using an Illumina MiSeq sequencer (San Diego, CA, USA). [7]. Paired-end reads were analyzed using QIIME2 (version 2019.10 obtained from http://qiime.org ...
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Obesity-related cardiometabolic disorders are driven by inflammation, oxidative stress, and gut dysbiosis. Green tea catechins protect against cardiometabolic disorders by anti-inflammatory, antioxidant, and prebiotic activities. However, whether obesity alters catechin bioavailability remains unknown. We hypothesized that obesity would decrease catechin bioavailability due to altered gut microbiota composition. Obese and healthy persons completed a pharmacokinetics trial in which a confection formulated with green tea extract (GTE; 58% epigallocatechin gallate, 17% epigallocatechin, 8% epicatechin, 6% epicatechin gallate) was ingested before collecting plasma and urine at timed intervals for up to 24 h. Stool samples were collected prior to confection ingestion. Catechins and γ-valerolactones were assessed by LC-MS. Obesity reduced plasma area under the curve (AUC0-12h) by 24–27% and maximum plasma concentrations by 18–36% for all catechins. Plasma AUC0-12h for 5′-(3′,4′-dihydroxyphenyl)-γ-valerolactone and 5′-(3′,4′,5′-trihydroxyphenyl)-γ-valerolactone, as well as total urinary elimination of all catechins and valerolactones, were unaffected. ⍺-Diversity in obese persons was lower, while Slackia was the only catechin-metabolizing bacteria that was altered by obesity. Ascorbic acid and diversity metrics were correlated with catechin/valerolactone bioavailability. These findings indicate that obesity reduces catechin bioavailability without affecting valerolactone generation, urinary catechin elimination, or substantially altered gut microbiota populations, suggesting a gut-level mechanism that limits catechin absorption.
... It has been shown that dimethoxy resveratrol derivatives also affect gut microbiota, especially the abundance of Akkermansia muciniphila, leading to an improvement in insulin sensitivity [229][230][231]; on the other hand, a natural flavanone glycoside increased the genus Akkermansia and expression of tight junction proteins, and reduced metabolic endotoxemia in mice fed with a high-fat diet [231,232]. Supplementation with resveratrol, quercetin and other flavonoids increased the abundance of Lactobacillus and Bifidobacterium and decreased the genes' expression related to fatty acids synthesis, adipogenesis and lipogenesis in mice fed with a high-fat diet [231][232][233][234][235]. Catechins prevented an increase in toll-like receptor 4 (TLR4)/NFκB-dependent inflammatory genes [233]. ...
... It has been shown that dimethoxy resveratrol derivatives also affect gut microbiota, especially the abundance of Akkermansia muciniphila, leading to an improvement in insulin sensitivity [229][230][231]; on the other hand, a natural flavanone glycoside increased the genus Akkermansia and expression of tight junction proteins, and reduced metabolic endotoxemia in mice fed with a high-fat diet [231,232]. Supplementation with resveratrol, quercetin and other flavonoids increased the abundance of Lactobacillus and Bifidobacterium and decreased the genes' expression related to fatty acids synthesis, adipogenesis and lipogenesis in mice fed with a high-fat diet [231][232][233][234][235]. Catechins prevented an increase in toll-like receptor 4 (TLR4)/NFκB-dependent inflammatory genes [233]. Wang et al. [234] found that Brazilian propolis increased the diversity and richness of gut microbiota populations against dextran sulfate sodium (DSS)-induced colitis in rats. ...
Article
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The incidence of allergic diseases and their complications are increasing worldwide. Today, people increasingly use natural products, which has been termed a “return to nature”. Natural products with healing properties, especially those obtained from plants and bees, have been used in the prevention and treatment of numerous chronic diseases, including allergy and/or inflammation. Propolis is a multi-component resin rich in flavonoids, collected and transformed by honeybees from buds and plant wounds for the construction and adaptation of their nests. This article describes the current views regarding the possible mechanisms and multiple benefits of flavonoids in combating allergy and allergy-related complications. These benefits arise from flavonoid anti-allergic, anti-inflammatory, antioxidative, and wound healing activities and their effects on microbe-immune system interactions in developing host responses to different allergens. Finally, this article presents various aspects of allergy pathobiology and possible molecular approaches in their treatment. Possible mechanisms regarding the antiallergic action of propolis on the microbiota of the digestive and respiratory tracts and skin diseases as a method to selectively remove allergenic molecules by the process of bacterial biotransformation are also reported.
... TLR4 plays an essential role in the mucosal inflammation associated with gut microbiota, and is a lucrative target for mitigating intestine-derived pathological insults associated with metabolic disease [185][186][187]. Mice lacking TLR-4 are substantially less likely to develop colitis-related cancer [188]. ...
... The consumption of polyphenol-rich food has been implicated in reducing cancer risks by mechanisms associated with improvements in gut microbiota. We have demonstrated that catechin-rich green tea can limit the clinical progression from nonalcoholic steatohepatitis to HCC by mitigating hepatic inflammation and pro-carcinogenic responses [232], in association with mitigating GI and hepatic inflammation, gut barrier dysfunction, and favorable modulation of gut microbial population, diversity, and metabolic functions [185][186][187]. The mechanism through which a polyphenolic-rich diet can be preventive of carcinogenesis through the favorable modulation of microbiota can include the modulation of hormonal regulation, limiting oxidative and inflammatory injury, and maintaining cellular proliferative/apoptotic homeostasis [233]. ...
Article
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Helicobacter pylori infection is the only well-established bacterial cause of cancer. However, due to the integral role of tissue-resident commensals in maintaining tissue-specific immunometabolic homeostasis, accumulated evidence suggests that an imbalance of tissue-resident microbiota that are otherwise considered as commensals, can also promote various types of cancers. Therefore, the present review discusses compelling evidence linking tissue-resident microbiota (especially gut bacteria) with cancer initiation and progression. Experimental evidence supporting the cancer-causing role of gut commensal through the modulation of host-specific processes (e.g., bile acid metabolism, hormonal effects) or by direct DNA damage and toxicity has been discussed. The opportunistic role of commensal through pathoadaptive mutation and overcoming colonization resistance is discussed, and how chronic inflammation triggered by microbiota could be an intermediate in cancer-causing infections has been discussed. Finally, we discuss microbiota-centric strategies, including fecal microbiota transplantation, proven to be beneficial in preventing and treating cancers. Collectively, this review provides a comprehensive understanding of the role of tissue-resident microbiota, their cancer-promoting potentials, and how beneficial bacteria can be used against cancers.
... With regard to Akkermansia, a mucin-degrading bacterium, its adequate proportion is directly associated with the health of the intestinal mucosal barrier [107]. Another in vivo study demonstrated that a dietary supplementation with 2% (m/m) green tea extract for 8 weeks protected high-fat diet feeding mice from inflammation and endotoxin translocation [108]. The intestinal barrier protection of green tea extract may contribute, at least in part, to its ability to remodel gut microbial homeostasis, mainly manifested in enriching the overall bacterial diversity and decreasing F/B ratio [108]. ...
... Another in vivo study demonstrated that a dietary supplementation with 2% (m/m) green tea extract for 8 weeks protected high-fat diet feeding mice from inflammation and endotoxin translocation [108]. The intestinal barrier protection of green tea extract may contribute, at least in part, to its ability to remodel gut microbial homeostasis, mainly manifested in enriching the overall bacterial diversity and decreasing F/B ratio [108]. ...
Article
Tea represents an abundant source of naturally occurring polyphenols. Tea polyphenols (TPs) have received growing attentions for its wide consumption in the world, and more importantly its pleiotropic bioeffects for human health. After ingestion, TPs may undergo absorption and phase II reaction in the small intestine, and most undigested proportion would be submitted to the colon to interact with gut microbiota. Interactions between gut microbiota and TPs are bidirectional, including not only bacteria-mediated TPs metabolism, e.g., removal of gallic acid moiety and ring fission to release phenolic acid catabolites, but also TPs-based modification of bacterial profiles. Crosstalk between TPs and gut microbes may benefit for gut barrier function, for example, improvement of the intestinal permeability to alleviate inflammation. Moreover, by reshaping microbial composition and associated metabolites, TPs may exert a systemic protection on host metabolism, which contributes to improve certain chronic metabolic disorders. Given that, further understanding of the metabolic fate of TPs and interplay with gut microbiota as well as potential health-promoting effects are of great significance to development and application of tea and their polyphenolic components in the future as dietary supplements and/or functional ingredients in medical foods.
... Growing evidence suggests that tea and its metabolites could maintain gut health and attenuate obesity through exerting prebiotic-like effects and modulating the gut community structure (Guo et al. 2017). In obese mice, green tea extract, fermented green tea extract, green tea polyphenols, oolong tea polyphenols, Fuzhuan brick tea, ripened Pu-erh tea extract, decaffeinated green tea combined with black tea were observed to change the gut microbiota composition and ameliorate the dysbiosis mostly by decreasing the ratio of Firmicutes to Bacteroidetes (Seo et al. 2015;Cheng et al. 2018;Henning et al. 2018;Zhang et al. 2018;Dey et al. 2019;Lu et al. 2019). Other microorganisms and related intestinal function are also affected by tea. ...
... The green tea extract not only increased the gut microbial diversity but also improved the gut barrier function which inhibited the endotoxin translocation and reduced adipose Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) inflammation (Dey et al. 2019). In addition, the ripened Pu-erh tea extract reduced the weight gain and fat accumulation and increased the intestinal barrier integrity in obese mice. ...
Article
Obesity has become a global health concern. It increases the risk of several diseases, such as type 2 diabetes mellitus, nonalcoholic fatty liver disease, and certain cancers, which threatens human health and increases social economic burden. As one of the most consumed beverages, tea contains various phytochemicals with potent bioactive properties and health-promoting effects, such as antioxidant, immune-regulation, cardiovascular protection and anticancer. Tea and its components are also considered as potential candidates for anti-obesity. Epidemiological studies indicate that regular consumption of tea is beneficial for reducing body fat. In addition, the experimental studies demonstrate that the potential anti-obesity mechanisms of tea are mainly involved in increasing energy expenditure and lipid catabolism, decreasing nutrient digestion and absorption as well as lipid synthesis, and regulating adipocytes, neuroendocrine system and gut microbiota. Moreover, most of clinical studies illustrate that the intake of green tea could reduce body weight and alleviate the obesity. In this review, we focus on the effect of tea and its components on obesity from epidemiological, experimental, and clinical studies, and discuss their potential mechanisms.
... Altogether, GTE is a beneficial food constituent for preventing and treating obesity. A potential mechanism for the anti-obesity of GTE was attributed to the alteration of gut microbiota, based on observations of increased Bacteroides abundance in response to GTE treatment (82)(83)(84). Two mechanisms may be responsible for the beneficial effects of GTE on obesity via improving gut microbiota. One hypothesized mechanism may be the increased production of short chain fatty acids (SCFAs) and the inhibition of endotoxin formation and translocation, thus attenuating obesity-associated adipose inflammation and decreasing body weight (84,85). ...
... Two mechanisms may be responsible for the beneficial effects of GTE on obesity via improving gut microbiota. One hypothesized mechanism may be the increased production of short chain fatty acids (SCFAs) and the inhibition of endotoxin formation and translocation, thus attenuating obesity-associated adipose inflammation and decreasing body weight (84,85). Another hypothesized mechanism may be via gut microbiota-improved intestinal redox state (86). ...
Article
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Obesity has become one of the most serious chronic diseases threatening human health. Its occurrence and development are closely associated with gut microbiota since the disorders of gut microbiota can promote endotoxin production and induce inflammatory response. Recently, numerous plant extracts have been proven to mitigate lipid dysmetabolism and obesity syndrome by regulating the abundance and composition of gut microbiota. In this review, we summarize the potential roles of different plant extracts including mulberry leaf extract, policosanol, cortex moutan, green tea, honokiol, and capsaicin in regulating obesity via gut microbiota. Based on the current findings, plant extracts may be promising agents for the prevention and treatment of obesity and its related metabolic diseases, and the mechanisms might be associated with gut microbiota.
... Jumlah senyawa ini lebih banyak pada ekstrak segar dibanding hasil fermentasinya [33]. Sedangkan C. sinensis bekerja dengan menurunkan endotoksin yang diduga mampu mencegah obesitas terinduksi endotoksin [34]. Sebanyak 4 senyawa golongan biflavonoid pada G. biloba berefek menghambat enzim PL, sehingga menimbulkan efek antiobesitas [22]. ...
Article
Obesitas adalah salah satu ancaman kesehatan yang sangat serius dan dihadapi semua negara. Masalah kesehatan ini sering berasosiasi dengan penyakit lain seperti diabetes dan gangguan kardiovaskuler. Penyebab obesitas pada seseorang bervariasi mulai dari genetik sampai gaya hidup. Didukung konsep back to nature dan pemanfaatan kekayaan nabati mendorong masyarakat untuk menggunakan obat-obatan yang berasal dari alam sebagai alternatif terapi. Pada review ini, disajikan daftar tanaman herbal serta mekanisme kerjanya mengatasi obesitas yang disusun dalam bentuk narasi dari hasil penelusuran literatur di beberapa search engine seperti PubMed, ScienceDirect, SpringerLink dan Google Scholar menggunakan kata kunci “herbal treatment, obesity, medicine plant dan mechanism of herbal medicine”. Dari hasil penelusuran diperoleh sebanyak 35 artikel penelitian yang membahas berbagai jenis tanaman serta uji dan mekanisme kerja yang didukung dengan hasil laboratorium. Kesimpulannya, terdapat banyak tanaman herbal yang dapat dimanfaatkan untuk membantu mengatasi obesitas melalui berbagai target farmakologi, terutama melalui modulasi faktor kaskade pensinyalan seluler AMPK, faktor transkripsi PPARℽ, PPARα dan C/EBP atau protein-protein lipogenik seperti SREBP-1c, ACC, FAS, PL dan LPL.
... A disrupted mucus barrier and gut inflammation is strongly evidenced in the development of metabolic disorders such as obesity and diabetes, and microbial dysbiosis is suggested to play a role in these effects (Cani et al., 2007(Cani et al., , 2008Wang et al., 2012;Boutagy et al., 2016;Dey et al., 2019;Schroeder et al., 2020). Associations between the virome and these diseases have been more recently established. ...
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In the human gastrointestinal tract, the gut mucosa and the bacterial component of the microbiota interact and modulate each other to accomplish a variety of critical functions. These include digestion aid, maintenance of the mucosal barrier, immune regulation, and production of vitamins, hormones, and other metabolites that are important for our health. The mucus lining of the gut is primarily composed of mucins, large glycosylated proteins with glycosylation patterns that vary depending on factors including location in the digestive tract and the local microbial population. Many gut bacteria have evolved to reside within the mucus layer and thus encode mucus-adhering and -degrading proteins. By doing so, they can influence the integrity of the mucus barrier and therefore promote either health maintenance or the onset and progression of some diseases. The viral members of the gut – mostly composed of bacteriophages – have also been shown to have mucus-interacting capabilities, but their mechanisms and effects remain largely unexplored. In this review, we discuss the role of bacteriophages in influencing mucosal integrity, indirectly via interactions with other members of the gut microbiota, or directly with the gut mucus via phage-encoded carbohydrate-interacting proteins. We additionally discuss how these phage-mucus interactions may influence health and disease states.
... The derived metabolites exert additive protective effects against intestinal inflammation, improving the mucosa microenvironment status. GTE enhanced adipose inflammation and TJPs in the ileum and colon of HFD-induced obese mice, preventing metabolic disorders associated with obesity [112]. ...
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Akkermansia muciniphila is a mucosal symbiont considered a gut microbial marker in healthy individuals, as its relative abundance is significantly reduced in subjects with gut inflammation and metabolic disturbances. Dietary polyphenols can distinctly stimulate the relative abundance of A. muciniphila, contributing to the attenuation of several diseases, including obesity, type 2 diabetes, inflammatory bowel diseases, and liver damage. However, mechanistic insight into how polyphenols stimulate A. muciniphila or its activity is limited. This review focuses on dietary interventions in rodents and humans and in vitro studies using different phenolic classes. We provide critical insights with respect to potential mechanisms explaining the effects of polyphenols affecting A. muciniphila. Anthocyanins, flavan-3-ols, flavonols, flavanones, stilbenes, and phenolic acids are shown to increase relative A. muciniphila levels in vivo, whereas lignans exert the opposite effect. Clinical trials show consistent findings, and high intervariability relying on the gut microbiota composition at the baseline and the presence of multiple polyphenol degraders appear to be cardinal determinants in inducing A. muciniphila and associated benefits by polyphenol intake. Polyphenols signal to the AhR receptor and impact the relative abundance of A. muciniphila in a direct and indirect fashion, resulting in the restoration of intestinal epithelial integrity and homeostatic crosstalk with the gut microbiota by affecting IL-22 production. Moreover, recent evidence suggests that A. muciniphila participates in the initial hydrolysis of some polyphenols but does not participate in their complete metabolism. In conclusion, the consumption of polyphenol-rich foods targeting A. muciniphila as a pivotal intermediary represents a promising precision nutritional therapy to prevent and attenuate metabolic and inflammatory diseases.
... There is considerable interest in the potential health benefits of pro-and prebiotics (Liu et al., 2015b;Dey et al., 2019). Probiotics are live bacteria that are present for example in fermented foods, such as yogurt, sauerkraut and kimchi. ...
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Estrogen receptor alpha positive (ERα+) breast cancers are refractory to immune checkpoint blocker (ICB) monotherapy, while ICBs are part of a standard of care for triple negative breast cancers (TNBCs). Besides tumor ERα expression, another difference between the two types of breast cancers is that only ERα+ patients exhibit elevated tumor estradiol (E2) levels, compared with surrounding normal tissue. Recent evidence suggests that inhibition of ERα or activation of ERβ or G protein-coupled estrogen receptor (GPER) in immune cells in the tumor microenvironment (TME) increases tumor CD8+ T cell infiltration and boosts cancer ICB response. Ovarian and adipose-produced estrogens activate all three ERs equally, but plant estrogens (phytochemicals) preferentially activate ERβ or GPER. The gut microbiota is a key player in determining response to ICBs, and high abundance of Firmicutes and high fecal levels of short chain fatty acids (SCFAs) that are mainly produced by Firmicutes, are linked to improved effectiveness of ICB therapy. Interestingly, the gut microbiota of ERα+ breast cancer patients contain significantly lower abundance of Firmicutes species than the gut microbiota of TNBC patients. Many factors modify the gut microbiota, especially diet. The gut microbiota altering diets include (i) foods high in ERβ and GPER activating plant phytochemicals or (ii) SCFAs producing fiber that also reduces circulating estrogen levels, (iii) estrogen levels reducing fasting/caloric restriction, or (iv) ketogenic diet which reduces fecal SCFA levels but increases hepatic production of SCFA receptor activating ketone bodies. It is thus possible that certain foods or dietary patterns can modify both the gut microbiota and activation of the estrogen receptors in the tumor immune cells, and consequently regulate the effectiveness of ICB therapy against cancers.
... For example, an anthocyanin-enriched fraction isolated from highbush blueberries dose-dependently restored intestinal barrier function in vitro in response to an E. coli challenge, a model of gut barrier dysfunction [7]. In another study, a catechin-rich green tea extract attenuated high-fat dietinduced gut inflammation, permeability, and dysbiosis by modulating tight junction protein and hypoxia inducible factor-1α expression [8]. Epigallocatechin gallate, the primary flavan-3-ol in green tea, has also been shown to improve intestinal permeability, inflammation, injury, and tight junction expression in murine models [9,10]. ...
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Background Submaximal endurance exercise has been shown to cause elevated gastrointestinal permeability, injury, and inflammation, which may negatively impact athletic performance and recovery. Preclinical and some clinical studies suggest that flavonoids, a class of plant secondary metabolites, may regulate intestinal permeability and reduce chronic low-grade inflammation. Consequently, the purpose of this study was to determine the effects of supplemental flavonoid intake on intestinal health and cycling performance. Materials and methods A randomized, double-blind, placebo-controlled crossover trial was conducted with 12 cyclists (8 males and 4 females). Subjects consumed a dairy milk-based, high or low flavonoid (490 or 5 mg) pre-workout beverage daily for 15 days. At the end of each intervention, a submaximal cycling trial (45 min, 70% VO 2 max) was conducted in a controlled laboratory setting (23°C), followed by a 15-minute maximal effort time trial during which total work and distance were determined. Plasma samples were collected pre- and post-exercise (0h, 1h, and 4h post-exercise). The primary outcome was intestinal injury, assessed by within-subject comparison of plasma intestinal fatty acid-binding protein. Prior to study start, this trial was registered at ClinicalTrials.gov (NCT03427879). Results A significant time effect was observed for intestinal fatty acid binding protein and circulating cytokines (IL-6, IL-10, TNF-α). No differences were observed between the low and high flavonoid treatment for intestinal permeability or injury. The flavonoid treatment tended to increase cycling work output (p = 0.051), though no differences were observed for cadence or total distance. Discussion Sub-chronic supplementation with blueberry, cocoa, and green tea in a dairy-based pre-workout beverage did not alleviate exercise-induced intestinal injury during submaximal cycling, as compared to the control beverage (dairy-milk based with low flavonoid content).
... In this study, it was observed that GBP contained a substantial amount of catechin (44.71 mg·L −1 ± 1.49), a flavonoid that can be metabolized by gut microbiota to generate hydroxy phenylacetic and hydroxyphenyl propionic acids (Shortt et al. 2018). Previous studies demonstrated that catechin promoted the growth of Bifidobacterium, Akermancia, and Roseburia in mice fed with a high-fat diet after the consumption of green tea polyphenols (Dey et al. 2019;Ma et al. 2019). It was also notable that procyanidin B2 content was found in both byproducts (12.97 mg·L −1 ± 0.33 for PBP and 13.88 mg·L −1 ± 0.72 for GBP). ...
Article
This study investigated the prebiotic potential of by-products from Puçá (Mouriri elliptica Mart) and Gabiroba (Campomanesia adamantium (Cambess.) O. Berg) (PBP and GBP). The fermentative capacity of Lactobacillus acidophilus LA-05, Lacticaseibacillus casei L-26, and Bifidobacterium animalis subsp. lactis BB-12 was evaluated on PBP and GBP extracts. Their prebiotic activity scores were evaluated in the presence of two strains of Escherichia coli. PBP and GBP contain high levels of dietary fiber and significant content of phenolic compounds such as catechin and procyanidin B2. Probiotic cultivation in media with PBP and GBP showed increased bacterial counts and decreased pH values. Positive probiotic activity scores were found for all strains, such as increased production of short-chain fatty acids and consumption of glucose and fructose over time, indicating high metabolic activities. Therefore, the PBP and GBP have characteristics that indicate their prebiotic potential, and potentially are interesting components to increase the nutritional value of foods.
... In vitro, catechin attenuates the production of pro-inflammatory cytokines, including TNF-α, IL-1 β, nitric oxide synthase, metalloproteinase 9 (MMP-9), MCP-1, and cyclooxygenase-2 and inhibits the TLR4-MyD88-mediated MAPK signaling pathway [81 ,84] . A rich source of catechins in green tea presented distinct actions regarding the TLR4 pathway in the intestinal segments of an experimental obesity model [85] . Despite decreasing the messenger RNA (mRNA) levels of TNF-α in the jejunum, ileum, and colon, mRNA levels of TLR4 and CD14 were decreased only in the ileum and colon after green tea extract intervention. ...
Article
Chronic inflammation is associated with the development and progression of several non-communicable diseases (NCDs), such as diabetes, cardiovascular disease, chronic kidney disease, cancer, and non-alcoholic fatty liver disease. Evidence suggests that pattern recognition receptors (PRRs) that identify pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) are crucial in chronic inflammation. Among the PRRs, Toll-like receptor 4 (TLR4) stimulates several inflammatory pathway agonists, such as the nuclear factor-κB (NF-κB), interferon regulator factor 3 (IRF3), and nod-like receptor pyrin domain containing 3 (NLRP3) pathways, that consequently trigger the expression of pro-inflammatory biomarkers, increasing the risk of NCD development and progression. Currently, studies have focused on the antagonistic potential of bioactive compounds, following the concept of food as a medicine, in which nutritional strategies may mitigate inflammation via TLR4 modulation. Thus, this narrative review discusses preclinical evidence concerning bioactive compounds from fruit, vegetable, spice, and herb extracts (curcumin, resveratrol, catechin, cinnamaldehyde, emodin, ginsenosides, quercetin, allicin, and caffeine) that may regulate the TLR4 pathway and reduce the inflammatory response. Bioactive compounds can inhibit TLR4-mediated inflammation through gut microbiota modulation, improvement of intestinal permeability, inhibition of lipopolysaccharide (LPS)-TLR4 binding, and decreasing TLR4 expression by modulation of microRNAs and antioxidant pathways. The responses directly mitigated inflammation, especially NF-κB activation and inflammatory cytokines release. These findings should be considered for further clinical studies on inflammation-mediated diseases.
... It has been reported that EGCG pre-treatment can effectively prevent the increase of epithelial cell permeability induced by IFN-γ and IL-4 (46). In addition, catechins can improve the intestinal microbial environment, thereby reducing the intestinal barrier in obese mice (47). In conclusion, catechins play an important role in intestinal barrier protection. ...
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The current research on interaction between catechin and protein has focused on non-covalent crosslinking, however, the mechanism of free radical-induced crosslinking between catechin and β-lactoglobulin (BLG) is not known. In this study, BLG bound to four catechins [epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG)]. The structure change of complex was investigated by circular dichroism spectroscopy, ultraviolet-visible (UV-vis) spectroscopy and Acid and 8-Anilino-1-naphthalenesulfonic acid (ANS) fluorescence spectroscopy. M cell model was constructed to evaluate the transintestinal epithelial transport capacity of complex digestive products. The results showed that catechins were covalently bound to BLG by C-S and C-N bonds and their binding content was EGCG>EGC>ECG>EC. Moreover, catechins could change the secondary structure of BLG, with the decrease of α-helix and reduction of the irregular coilings, which leads to the loose spatial structure of the protein. Moreover, the catechin could enhance further the digestibility of BLG. Transport capacity of digestive products of M cell model was about twice of that of the Caco-2 cell model, indicating that M cell model had better antigen transport capacity. The difference between groups indicated that the transport efficiency of digestive products was decreased with the presence of catechin, in which BLG-EGCG and BLG-EGC groups were transported more strong than those of BLG-EC and BLG-ECG groups. The transport efficiency of BLG-catechin complexes were lower than that of BLG, indicating that catechin had the protective and repair roles on intestinal barrier permeability.
... Green tea shows good anti-inflammatory activity, which is due to the high level of tea polyphenols . Green tea extract is found to prevent obesity (Dey et al., 2019), suggesting that the strong antioxidant properties of green tea can be utilized. Plenty of evidence reveals that the health effects due to drinking tea may correlate with the classification of tea. ...
Article
The classification of tea products is nowadays mainly determined by sensory assessment and chemical analysis methods. These methods are subjective, time-consuming, and laborious. In this work, a rapid analytical method for tea classification was proposed on the basis of X-ray photoelectron spectroscopy (XPS) and quantum chemical calculation. A total of 56 kinds of tea products were studied. By utilizing the data fusion strategy, the correlation between XPS peak parameters and tea characteristics was established. The quantum chemical calculations of the core-level ionization potentials deepen the understanding of the XPS features. The binding energy of the main fitted peak for O 1s, BE1O1s, was found to have a good correlation with tea polyphenols contents, which can be used to classify tea products into six tea types (black, dark, green, oolong, white, and yellow tea) with an accuracy greater than 90%. The results suggest that the proposed XPS method is suitable for the rapid discrimination of tea classification, which contributes to the efficient application of tea.
... Many studies on animals confirm that anthocyanins, anthocyanidins and catechins stimulate the growth of health-promoting bacteria such as Akkermansia, Lactobacillus and Bifidobacterium and Roseburia [105][106][107][108] This has also been confirmed in clinical trials. Anthocyanins consumed with wild blueberry drink caused an increase in Lactobacillus acidophilus and Bifidobacterium after 6 weeks of application [109]. ...
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Abstract: Imitating the human digestive system as closely as possible is the goal of modern science. The main reason is to find an alternative to expensive, risky and time-consuming clinical trials. Of particular interest are models that simulate the gut microbiome. This paper aims to characterize the human gut microbiome, highlight the importance of its contribution to disease, and present in vitro models that allow studying the microbiome outside the human body but under near-natural conditions. A review of studies using models SHIME, SIMGI, TIM-2, ECSIM, EnteroMix, and PolyfermS will provide an overview of the options available and the choice of a model that suits the researcher’s expectations with advantages and disadvantages. Keywords: microbiome; microbiota; in vitro models; human gut; nutraceuticals
... Catechins inhibit the growth of certain pathogenic bacteria, such as Clostridium difficile and Staphylococcus spp., and may also stimulate the growth of beneficial Bifidobacterium bacteria [81]. Green tea extract, which is rich in catechins, especially EGCG, has been shown to improve the integrity of the intestinal barrier by reducing the translocation of gut-derived endotoxin and thus the resulting proinflammatory response in both animals and humans [87][88][89]. Campferol, which is present in tea leaves, improves the integrity of the intestinal barrier and inhibits inflammation in the intestines by reducing the activation of the TLR4/NF-κB pathway, and prevents the obesity-related gut dysbiosis [90]. ...
Article
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Type 1 diabetes mellitus (T1DM) is a disease marked by oxidative stress, chronic inflammation, and the presence of autoantibodies. The gut microbiota has been shown to be involved in the alleviation of oxidative stress and inflammation as well as strengthening immunity, thus its’ possible involvement in the pathogenesis of T1DM has been highlighted. The goal of the present study is to analyze information on the relationship between the structure of the intestinal microbiome and the occurrence of T1DM. The modification of the intestinal microbiota can increase the proportion of SCFA-producing bacteria, which could in turn be effective in the prevention and/or treatment of T1DM. The increased daily intake of soluble and non-soluble fibers, as well as the inclusion of pro-biotics, prebiotics, herbs, spices, and teas that are sources of phytobiotics, in the diet, could be important in improving the composition and activity of the microbiota and thus in the prevention of metabolic disorders. Understanding how the microbiota interacts with immune cells to create immune tolerance could enable the development of new therapeutic strategies for T1DM and improve the quality of life of people with T1DM.
... We have previously identified a combination of tea polyphenol EGCG and probiotic bacteria Lactobacillus fermentum that can differentially and beneficially modulate the functions of the aging immune system in mice as opposed to individual treatments of EGCG or probiotic bacteria [177]. Similarly, several studies have shown that consumption of green or black tea polyphenols can modulate the gut microbiota which positively impacts the host health [178][179][180][181][182][183]. In addition, there appears to be evidence that the health beneficial effects of polyphenol-rich sources, such as in tea, may actually be mediated by the reciprocal interactions between polyphenols and the gut microbiome. ...
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A cellular senescence-centric understanding of biological aging and age-related chronic diseases is rapidly emerging. As a result, strategies aimed at mitigating the deleterious aspects of cellular senescence are increasingly becoming desirable. Tea is a globally admired and nutrient-rich beverage that not only refreshes the senses but is also implicated in several health beneficial effects including the extension of organismal healthspan and lifespan. The present review discusses the emerging anti-cellular senescence attributes of tea consumption and provides a perspective that the anti-aging aspects of tea should be studied in the purview of cellular senescence. Current understanding of the integrative effects of the immune system and gut microbiome on cellular senescence have also been discussed with the rationale of mitigatory effects of tea. Future research directions and recommendations have been provided which may ultimately help augment tea-oriented successful and healthy aging approaches.
... Bacterial DNA was extracted using a QIAamp Fast DNA Stool Mini Kit (Qiagen, Hilden, Germany) as described [38]. Then, the V4-V5 hypervariable region of the 16S rRNA gene was amplified by PCR to prepare amplicon libraries followed by MiSeq sequencing (Illumina, San Diego, CA, USA) [39]. Paired-end reads (2 × 300 paired-end protocol) were analyzed using QIIME2 (version 2020.2) [40]. ...
Article
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Poor diet quality influences cardiometabolic risk. Although potatoes are suggested to adversely affect cardiometabolic health, controlled trials that can establish causality are limited. Consistent with potatoes being rich in micronutrients and resistant starch, we hypothesized that their inclusion in a Dietary Guidelines for Americans (DGA)-based dietary pattern would improve cardiometabolic and gut health in metabolic syndrome (MetS) persons. In a randomized cross-over trial, MetS persons (n = 27; 32.5 ± 1.3 year) consumed a DGA-based diet for 2 weeks containing potatoes (DGA + POTATO; 17.5 g/day resistant starch) or bagels (DGA + BAGEL; 0 g/day resistant starch) prior to completing oral glucose and gut permeability tests. Blood pressure, fasting glucose and insulin, and insulin resistance decreased (p < 0.05) from baseline regardless of treatment without any change in body mass. Oral glucose-induced changes in brachial artery flow-mediated dilation, nitric oxide homeostasis, and lipid peroxidation did not differ between treatment arms. Serum endotoxin AUC0–120 min and urinary lactulose/mannitol, but not urinary sucralose/erythritol, were lower in DGA + POTATO. Fecal microbiome showed limited between-treatment differences, but the proportion of acetate was higher in DGA + POTATO. Thus, short-term consumption of a DGA-based diet decreases cardiometabolic risk, and the incorporation of resistant starch-containing potatoes into a healthy diet reduces small intestinal permeability and postprandial endotoxemia.
... Such a way of processing allows maintaining high amounts of antimicrobial and antioxidant phenolic compounds, which are absent in refined forms. In another study, the phenolic compounds obtained from green tea were shown to prevent the mouse intestine from alterations in TJ proteins and dysbiosis caused by HFD [61]. ...
Article
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Leaky gut syndrome is a medical condition characterized by intestinal hyperpermeability. Since the intestinal barrier is one of the essential components maintaining homeostasis along the gastrointestinal tract, loss of its integrity due to changes in bacterial composition, decreased expression levels of tight junction proteins, and increased concentration of pro-inflammatory cytokines may lead to intestinal hyperpermeability followed by the development of gastrointestinal and non-gastrointestinal diseases. Translocation of microorganisms and their toxic metabolites beyond the gastrointestinal tract is one of the fallouts of the leaky gut syndrome. The presence of intestinal bacteria in sterile tissues and distant organs may cause damage due to chronic inflammation and progression of disorders, including inflammatory bowel diseases, liver cirrhosis, and acute pancreatitis. Currently, there are no medical guidelines for the treatment or prevention of bacterial translocation in patients with the leaky gut syndrome; however, several studies suggest that dietary intervention can improve barrier function and restrict bacteria invasion. This review contains current literature data concerning the influence of diet, dietary supplements, probiotics, and drugs on intestinal permeability and bacterial translocation.
... All rights reserved the liver receives a larger influx of endotoxin in comparison to other tissues due to the portal vein. For instance, LPS concentration in the portal system has been reported to be 10 times greater versus concentrations in peripheral blood [100]. Though LPS is also absorbed with lipids, it effectively binds to lipoproteins in chylomicrons due to the action of LBP [101]. ...
Article
Systemic inflammation is associated with chronic disease and is purported to be a main pathogenic mechanism underlying metabolic conditions. Microbes harbored in the host gastrointestinal tract release signaling byproducts from their cell wall, such as lipopolysaccharides (LPS), which can act locally and, after crossing the gut barrier and entering circulation, also systemically. Defined as metabolic endotoxemia, elevated concentrations of LPS in circulation are associated with metabolic conditions and chronic disease. As such, measurement of LPS is highly prevalent in animal and human research investigating these states. Indeed, LPS can be a potent stimulant of host immunity but this response depends on the microbial species’ origin, a parameter often overlooked in both preclinical and clinical investigations. Indeed, the lipid A portion of LPS is mutable and comprises the main virulence and endotoxic component, thus contributing to the structural and functional diversity among LPSs from microbial species. In this review, we discuss how such structural differences in LPS can induce differential immunological responses in the host. Spurring metabolic endotoxemia, lipopolysaccharides from microbes in the gut act locally and systemically by crossing the gut barrier and entering host circulation. Lipopolysaccharides are associated with major chronic diseases and are a prevalent biomarker in animal and human research. However, just as microbes vary, so do their products. Structural differences in LPS can induce differential health responses in the host.
... 5 The beneficial effects of phenolic acids on intestinal leakage are currently attracting increasing attention. 6,7 Phenolic acids are classified into hydroxybenzoic acid derivatives [e.g. protocatechuic acid (PCA), vanillic acid (VA) and hippuric acid (HA)] and hydroxycinnamic acid derivatives [e.g. ...
Article
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Phenolic acids play an active role in protecting the intestinal barrier, the structural integrity and function of which are crucial for host health. In the present study, we aimed to identify phenolic compounds that protect the intestine and explore the underlying mechanisms. We performed an imaging-based, quantitative, high-content screening (using Caco-2 and LS174T incubated with lipopolysaccharide/palmitic acid, respectively) to identify phenolic acids that could improve the mucosal barrier. We found that chlorogenic acid (CGA), 5-caffeoylquinic acid, protocatechuic acid, and caffeic acid alleviated intestinal barrier disruption. Furthermore, CGA increased transepithelial electrical resistance (TEER) and decreased paracellular permeability. Mechanistically, CGA inhibited the activation of myosin light chain kinase (MLCK) and Rho-associated kinase 1 (ROCK1) signals, thereby downregulating the expression of the downstream molecules phosphorylated myosin phosphatase target subunit 1 (p-MYPT1), MLCK, and phosphorylated myosin light chain (p-MLC), and upregulating the expression of tight junction proteins. In addition, CGA alleviated endoplasmic reticulum (ER) stress by inhibiting the expression levels of ER markers [glucose-regulated protein78 (GRP78) and C/EBP homologous protein (CHOP)] and the nuclear translocation of activating transcription factor 6 (ATF6), thereby promoting the expression of mucin [mucin 2 (Muc2), mucin 5AC (MUC5AC)] and secretory factor trefoil factor family 3 (TFF3) proteins. In summary, we identified four substances that can stabilise intestinal homeostasis. Of these, CGA protects the intestinal barrier by inhibiting ROCK/MLCK signalling pathways and relieving ER stress. These findings highlight the importance of rapidly screening potential active ingredients that benefit the intestinal barrier and provide a theoretical basis for enteral nutrition.
... In recent years, the role of the intestine in the development of obesity and T2D is increasingly recognized. Studies conducted in various animal models provide convincing evidence that inflammation originates in the intestine due to the modulation of gut barrier function leading to metabolic endotoxemia (14)(15)(16)(17)(18). Metabolic endotoxemia refers to a diet-induced 2-3 fold increase in gut-derived plasma lipopolysaccharide (LPS) level (14), which may result in low-grade systemic and tissue inflammation, contributing to a metabolic disease phenotype (14,15,(19)(20)(21)(22). Metabolic endotoxemia is indicative of decreased intestinal epithelial barrier function, also referred to as "leaky gut" syndrome ( Figure 1), which allows undesirable luminal immunogens, such as LPS, but also bacterial DNA and RNA and to some degree viable bacteria, to cross into the blood and lymphatic system (14,29). ...
Article
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Noncommunicable diseases, such as type 2 diabetes (T2D), place a burden on healthcare systems worldwide. The rising prevalence of obesity, a major risk factor for T2D, is mainly attributed to the adoption of Westernized diets and lifestyle, which cause metabolic dysfunction and insulin resistance. Moreover, diet may also induce changes in the microbiota composition, thereby affecting intestinal immunity. The critical role of intestinal immunity and intestinal barrier function in the development of T2D is increasingly acknowledged, however, limited studies have investigated the link between intestinal function and metabolic disease. In this review, studies reporting specific roles of the intestinal immune system and intestinal epithelial cells (IECs) in metabolic disease are highlighted. Innate chemokine signaling, eosinophils, immunoglobulin A (IgA), T helper (Th) 17 cells and their cytokines were associated with obesity and/or dysregulated glucose homeostasis. Intestinal epithelial cells (IECs) emerged as critical modulators of obesity and glucose homeostasis through their effect on lipopolysaccharide (LPS) signaling and decontamination. Furthermore, IECs create a link between microbial metabolites and whole-body metabolic function. Future in depth studies of the intestinal immune system and IECs may provide new opportunities and targets to develop treatments and prevention strategies for obesity and T2D.
... In this same study, the authors concluded that an anthocyanins-rich formula improves hyperglycemia and insulin resistance in obese mice fed with a high-fat diet by modulating glucose metabolism in the liver and skeletal muscle [10]. Resveratrol and green tea have shown efficacy in decreasing weight gain induced by OLZ in rodents [20]. This evidence is important since OLZ-induced diabetes is a severe, lifethreatening condition with very limited prophylactic interventions. ...
Article
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Type 2 diabetes and obesity are major problems worldwide and dietary polyphenols have shown efficacy to ameliorate signs of these diseases. Anthocyanins from berries display potent antioxidants and protect against weight gain and insulin resistance in different models of diet- induced metabolic syndrome. Olanzapine is known to induce an accelerated form of metabolic syndrome. Due to the aforementioned, we evaluated whether delphinidin-3,5-O-diglucoside (DG) and delphinidin-3-O-sambubioside-5-O-glucoside (DS), two potent antidiabetic anthocyanins isolated from Aristotelia chilensis fruit, could prevent olanzapine-induced steatosis and insulin resistance in liver and skeletal muscle cells, respectively. HepG2 liver cells and L6 skeletal muscle cells were co- incubated with DG 50 μg/mL or DS 50 μg/mL plus olanzapine 50 μg/mL. Lipid accumulation was determined in HepG2 cells while the expression of p-Akt as a key regulator of the insulin-activated signaling pathways, mitochondrial function, and glucose uptake was assessed in L6 cells. DS and DG prevented olanzapine-induced lipid accumulation in liver cells. However, insulin signaling impairment induced by olanzapine in L6 cells was not rescued by DS and DG. Thus, anthocyanins modulate lipid metabolism, which is a relevant factor in hepatic tissue, but do not significantly influence skeletal muscle, where a potent antioxidant effect of olanzapine was found.
... As reported in previous studies, green tea has potential antiobesity properties (Dey et al., 2019;Dinh et al., 2019;Westerterp-Plantenga, 2010). These properties are attributed to several bioactive compounds, such as EC, EGC, ECG, and EGCG (Hayat et al., 2015;Li et al., 2020). ...
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Adipose browning leads to increased energy expenditure and reduced adiposity and has, therefore, become an attractive therapeutic strategy for obesity. In this study, we elucidated the effect of green tea aqueous extract (GTAE) on the browning of inguinal white adipose tissue (Ing‐WAT) and brown adipose tissue (BAT) in high‐fat diet (HFD)‐fed mice. The main phytochemical components identified in GTAE through high‐performance liquid chromatography (HPLC) included (−)‐gallocatechin, (−)‐epigallocatechin, (−)‐catechin, (−)‐epigallocatechin‐3‐gallate, caffeine, (−)‐epicatechin, (−)‐gallocatechin gallate, and (−)‐epicatechin‐3‐gallate. Daily supplementation with 1% GTAE for 12 weeks markedly reduced bodyweight gain, systemic inflammation, oxidative stress, and improved insulin resistance. Additionally, histological analysis revealed that dietary supplementation with 1% GTAE reversed HFD‐induced adipocyte size and hepatic steatosis. These effects were associated with activation of browning in the Ing‐WAT and BAT, which mediate systemic metabolic dysfunction in HFD‐fed mice. Taken together, our data support the use of GTAE, a natural product, for the attenuation of obesity through the activation of fat browning. The present study found that mice fed a high‐fat diet showed significantly lower weight gain upon GTAE administration than their control counterparts. In addition, GTAE ameliorated the high‐fat diet‐induced hepatic steatosis, insulin resistance, and low‐systematic inflammatory. These effects were associated with browning activation in the Ing‐WAT and BAT.
Article
As it is well known, the gut is one of the primary sites in any host for xenobiotics, and the many microbial metabolites responsible for the interactions between the gut microbiome and the host. However, there is a growing concern about the negative impacts on human health induced by toxic xenobiotics. Metabolomics, broadly including lipidomics, is an emerging approach to studying thousands of metabolites in parallel. In this review, we summarized recent advancements in mass spectrometry (MS) technologies in metabolomics. In addition, we reviewed recent applications of MS-based metabolomics for the investigation of toxic effects of xenobiotics on microbial and host metabolism. It was demonstrated that metabolomics, gut microbiome profiling, and their combination have a high potential to identify metabolic and microbial markers of xenobiotic exposure and determine its mechanism. Further, there is increasing evidence supporting that reprogramming the gut microbiome could be a promising approach to the intervention of xenobiotic toxicity.
Chapter
Non-communicable diseases, such as cardiovascular disease, cancer, diabetes, obesity, and hypertension, represent the cause of 60% of all deaths around the globe. With proper diet and natural dietary antioxidant supplements, these diseases can be prevented by up to 40% according to the British Nutrition Foundation. This book provides a comprehensive overview of the literature on the health benefits of natural dietary antioxidant supplements. It presents state-of-the-art research and information as well as the global regulations, labelling, and health claims of natural dietary antioxidant supplements. Written by expert authors, the wealth of research is arranged by disease type rather than by supplement type making it much more useful to the reader. Filling a gap in the literature, the book is aimed at researchers and professionals working in food chemistry, nutrition, and health benefits.
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The influx of intestinal bacteria-derived lipopolysaccharide (LPS) into the blood has attracted attention as a cause of diseases. The aim of this study is investigating the associations between the influx of LPS, dietary factors, gut microbiota, and health status in the general adult population. Food/nutrient intake, gut microbiota, health status and plasma LPS-binding protein (LBP; LPS exposure indicator) were measured in 896 residents (58.1% female, mean age 54.7 years) of the rural Iwaki district of Japan, and each correlation was analyzed. As the results, plasma LBP concentration correlated with physical (right/left arms’ muscle mass [β = −0.02, −0.03]), renal (plasma renin activity [β = 0.27], urine albumin creatinine ratio [β = 0.50]), adrenal cortical (cortisol [β = 0.14]), and thyroid function (free thyroxine [β = 0.05]), iron metabolism (serum iron [β = −0.14]), and markers of lifestyle-related diseases (all Qs < 0.20). Plasma LBP concentration were mainly negatively correlated with vegetables/their nutrients intake (all βs ≤ −0.004, Qs < 0.20). Plasma LBP concentration was positively correlated with the proportion of Prevotella (β = 0.32), Megamonas (β = 0.56), and Streptococcus (β = 0.65); and negatively correlated with Roseburia (β = −0.57) (all Qs < 0.20). Dietary factors correlated with plasma LBP concentration correlated with positively (all βs ≥ 0.07) or negatively (all βs ≤ −0.07) the proportion of these bacteria (all Qs < 0.20). Our results suggested that plasma LBP concentration in the Japanese general adult population was associated with various health issues, and that dietary habit was associated with plasma LBP concentration in relation to the intestinal bacteria.
Article
Nerium oleander L. is a medicinal plant, used for the treatment of cancers and hyperglycemia across the world, especially in Indian sub-continent, Turkey, Morocco, and China. Although clinical studies supporting its pharmacological effects remain critically underexplored, accidental and intentional consumption of any part of the plant causes fatal toxicity in animals and humans. While the polyphenolic fraction of oleander leaves has been attributed to its pre-clinical pharmacological activities, the presence of diverse cardiac glycosides (especially oleandrin) causes apoptosis to cancer cells in vitro and results in clinical signs of oleander poisoning. Thus, the dual pharmacological and toxicological role of oleander is a perplexing dichotomy in phytotherapy. The current investigative review, therefore, intended to analyze the intrinsic and extrinsic factors that likely contribute to this conundrum. Especially by focusing on gut microbial diversity, abundance, and metabolic functions, oleander-associated pharmacological and toxicological studies have been critically analyzed to define the dual effects of oleander. Electronic databases were extensively screened for relevant research articles (including pre-clinical and clinical) related to oleander bioactivities and toxicity. Taxonomic preference was given to the plant N. oleander L. and synonymous plants as per 'The World Flora Online' database (WCSP record #135196). Discussion on yellow oleander (Cascabela thevetia (L.) Lippold) has intentionally been avoided since it is a different plant. The review indicates that the gut microbiota likely plays a key role in differentially modulating the pharmacological and toxicological effects of oleander. Other factors identified influencing the oleander bioactivities include dose and mode of treatment, cardiac glycoside pharmacokinetics, host-endogenous glycosides, plant material processing and phytochemical extraction methods, plant genotypic variations, environmental effects on the phytochemical quality and quantity, gene expression variations, host dietary patterns and co-morbidity, etc. The arguments proposed are also relevant to other medicinal plants containing toxic cardiac glycosides.
Chapter
Coffee and tea are the most consumed beverages among the globe after water regarding their desirable organoleptic characteristics and well-demonstrated health benefits. A great number of the minor compounds present in coffee and tea have shown considerable bioactive potential; they can reduce inflammation by influencing metabolic processes and prevent cardiovascular diseases (CVD). These compounds regarding the coffee beans are the phenolic compounds (mainly chlorogenic acid and its derivatives), methylxanthines (mainly caffeine but also theophylline and theobromine), diterpenes (cafestol and kahweol), and trigonelline (the precursor of nicotinic acid). The concentration of them can differ significantly depending on the type of the bean and the processing they undergo. Regarding the bioactive compounds that can be found in tea leaves, the polyphenols (catechins in green tea, oxidized polyphenols such as theaflavins in black tea), l-theanine, and caffeine are the most abundant. Although there is only one type of tea leaves from which all types of tea are produced (e.g., black tea, green tea, and oolong tea), the production process for each tea type differs to a great extent providing every tea type with unique bioactive composition and therefore unique health benefits. This book chapter will define the differences in the chemical composition of different coffee and tea types, and it will summarize the findings of literature regarding their bioactive potential. According to these findings, moderate consumption of coffee (up to three cups per day) and tea (three to six cups per day) can maximize their effect on the prevention of inflammatory conditions and CVD.
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Microbial exopolysaccharides (EPS) are extracellular carbohydrate polymers forming capsules or slimy coating around the cells. EPS can be secreted by various bacterial genera that can help bacterial cells in attachment, environmental adaptation, stress tolerance and are an integral part of microbial biofilms. Several gut commensals (e.g., Lactobacillus, Bifidobacterium) produce EPS that possess diverse bioactivities. Bacterial EPS also has extensive commercial applications in the pharmaceutical and food industries. Owing to the structural and functional diversity, genetic and metabolic engineering strategies are currently employed to increase EPS production. Therefore, the current review provides a comprehensive overview of the fundamentals of bacterial exopolysaccharides, including their classification, source, biosynthetic pathways, and functions in the microbial community. The review also provides an overview of the diverse bioactivities of microbial EPS, including immunomodulatory, anti-diabetic, anti-obesity, and anti-cancer properties. Since several gut microbes are EPS producers and gut microbiota helps maintain a functional gut barrier, emphasis has been given to the intestinal-level bioactivities of the gut microbial EPS. Collectively, the review provides a comprehensive overview of microbial bioactive exopolysaccharides.
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Obesity is associated with an imbalance of micro-and macro-nutrients, dysbiosis, and a “leaky” gut phenomenon. Polyphenols, such as curcumin, resveratrol, and anthocyanin may alleviate the systemic effects of obesity, potentially by improving gut microbiota, intestinal barrier integrity (IBI), and zinc homeostasis. The essential micronutrient zinc plays a crucial role in the regulation of enzymatic processes, including inflammation, maintenance of the microbial ecology, and intestinal barrier integrity. In this review, we focus on IBI– which prevents intestinal lipopolysaccharide (LPS) leakage – as a critical player in polyphenol-mediated protective effects against obesity-associated white adipose tissue (WAT) inflammation. This occurs through mechanisms that block the movement of the bacterial endotoxin LPS across the gut barrier. Available research suggests that polyphenols reduce WAT and systemic inflammation via crosstalk with inflammatory NF-κB, the mammalian target of rapamycin (mTOR) signaling and zinc homeostasis.
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Background: About 50 000 new cases of cancer in the United States are attributed to obesity. The adverse effects of obesity on breast cancer may be most profound when affecting the early development; that is, in the womb of a pregnant obese mother. Maternal obesity has several long-lasting adverse health effects on the offspring, including increasing offspring's breast cancer risk and mortality. Gut microbiota is a player in obesity as well as may impact breast carcinogenesis. Gut microbiota is established early in life and the microbial composition of an infant's gut becomes permanently dysregulated because of maternal obesity. Metabolites from the microbiota, especially short chain fatty acids (SCFAs), play a critical role in mediating the effect of gut bacteria on multiple biological functions, such as immune system, including tumor immune responses. Recent findings: Maternal obesity can pre-program daughter's breast cancer to be more aggressive, less responsive to treatments and consequently more likely to cause breast cancer related death. Maternal obesity may also induce poor response to immune checkpoint inhibitor (ICB) therapy through increased abundance of inflammation associated microbiome and decreased abundance of bacteria that are linked to production of SCFAs. Dietary interventions that increase the abundance of bacteria producing SCFAs potentially reverses offspring's resistance to breast cancer therapy. Conclusion: Since immunotherapies have emerged as highly effective treatments for many cancers, albeit there is an urgent need to enlarge the patient population who will be responsive to these treatments. One of the factors which may cause ICB refractoriness could be maternal obesity, based on its effects on the microbiota markers of ICB therapy response among the offspring. Since about 40% of children are born to obese mothers in the Western societies, it is important to determine if maternal obesity impairs offspring's response to cancer immunotherapies.
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Obesity caused by poor eating habits has become a great challenge faced by public health organizations worldwide. Optimizing dietary intake and ingesting special foods containing biologically active substances (such as polyphenols, alkaloids, and terpenes) is a safe and effective dietary intervention to prevent the occurrence and development of obesity. Tea contains several active dietary factors, and daily tea consumption has been shown to have various health benefits, especially in regulating human metabolic diseases. Here, we reviewed recent advances in research on tea and its functional components in improving obesity-related metabolic dysfunction, and gut microbiota homeostasis and related clinical research. Furthermore, the potential mechanisms by which the functional components of tea could promote lipid-lowering and weight-loss effects by regulating fat synthesis/metabolism, glucose metabolism, gut microbial homeostasis, and liver function were summarized. The research results showing a "positive effect" or "no effect” objectively evaluate the lipid-lowering and weight-loss effects of the functional components of tea. This review provides a new scientific basis for further research on the functional ingredients of tea for lipid lowering and weight loss and the development of lipid-lowering and weight-loss functional foods and beverages derived from tea.
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The abundance of gut commensals has historically been associated with health-promoting effects despite the fact that the definition of good or bad microbiota remains condition-specific. The beneficial or pathogenic nature of microbiota is generally dictated by the dimensions of host-microbiota and microbe-microbe interactions. With the increasing popularity of gut micro-biota in human health and disease, emerging evidence suggests opportunistic infections promoted by those gut bacteria that are generally considered beneficial. Therefore, the current review deals with the opportunistic nature of the gut commensals and aims to summarise the concepts behind the occasional commensal-to-pathogenic transformation of the gut microbes. Specifically, relevant clinical and experimental studies have been discussed on the overgrowth and bacteraemia caused by commensals. Three key processes and their underlying mechanisms have been summarised to be responsible for the opportunistic nature of commensals, viz. improved colonisation fitness that is dictated by commensal-pathogen interactions and availability of preferred nutrients; pathoadaptive mutations that can trigger the commensal-to-pathogen transformation; and evasion of host immune response as a survival and proliferation strategy of the microbes. Collectively, this review provides an updated concept summary on the underlying mechanisms of disease causative events driven by gut commensal bacteria. ARTICLE HISTORY
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Rich in abundant polyphenols and dietary fiber, blueberry pomace is still a potential material for gut health. This study aimed to reuse blueberry pomace by lactic acid bacteria fermentation and evaluate the colonic barrier-improving functions of Lactobacillus casei-fermented blueberry pomace (FBP). Male C57BL/6 mice were fed with control or high fat diets. The changes of oxidative stress, inflammation, microbiota, short chain fatty acids (SCFAs), SCFAs receptors and barrier-related proteins in mice colon were evaluated. FBP attenuated the high fat diet-induced oxidative and inflammatory status in colon. Abundance of Bifidobacterium, Lactobacillus, Ruminococcus, Akkermansia and butyrate-producing bacteria, SCFAs concentration, expression of SCFAs receptors and regulation of barrier-related proteins in high fat diet mice were elevated through supplying FBP. These FBP-associated beneficial changes in high fat diet mice were mediated by the MAPK-NF-κB-MLCK signaling pathway. FBP shows colonic barrier-improving functions in high fat diet mice.
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Gut microbiota (GM) play important roles in multiple organ function, homeostasis and several diseases. More recently, increasing evidences have suggested that the compositional and functional alterations of GM play a crucial role in the accumulation of foam cells and the formation of atherosclerotic plaque in atherosclerosis. In particular, the effects of bacterial components and metabolites on innate and adaptive immune cells have been explored as the underlying mechanisms. Understanding the effects of GM and metabolites on immunoregulation are important for clinical therapy for atherosclerosis. Herein, we summarize the potential role of the GM (such as bacterial components lipopolysaccharide and peptidoglycan) and GM‐derived metabolites (such as short‐chain fatty acids, trimethylamine N‐oxide and bile acids) in the immunopathology of atherosclerosis. Based on that, we further discuss the anti‐atherosclerotic effects of GM‐directed dietary bioactive factors such as dietary fibers, dietary polyphenols and probiotics. Because of drug‐induced adverse events in anti‐inflammatory therapies, personalized dietary interventions would be potential therapies for atherosclerosis, and the interactions between GM‐derived products and immune cells should be studied further.
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Scope: Hawk tea, a non-Camellia tea, is an ancient tea drink from southwest China and has been proven to exhibit significant hypoglycaemic and lipid-lowering effects. The aim of this study was to evaluate whether Hawk tea extract (HTE) can improve obesity induced by a high-fat diet (HFD) in a mouse model and to determine whether its anti-obesity effects are related to improvements in lipid metabolism and the gut microbiota. Methods and results: We tested the ability of HTE to prevent obesity and regulate gut microbiota in C57BL/6J mice fed with a HFD. We found that HTE significantly reduced body weight, fat deposition, serum triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, and significantly increased serum levels of high-density lipoprotein cholesterol (HDL-C) induced by HFD. HTE also increased the levels of AMPK and ACC phosphorylation, up-regulated the expression of CPT-1, and downregulated the expression of SREBP1c and FAS. In addition, the administration of HTE significantly altered the composition of the gut microbiota, reduced the ratio of Firmicutes to Bacteroidetes, increased the relative abundance of Akkermansia muciniphila, Bacteroides-vulgatus, and Faecalibaculum_rodentium, and decreased the relative abundance of Desulfovibrionaceae and Lachnospiraceae. Conclusions: Collectively, our data demonstrate that HTE can prevent HFD-induced obesity by regulating the AMPK/ACC/SREBP1c signaling pathways and the gut microbiota.
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Catechins are a phytochemical present in plants such as tea leaves, beans, black grapes, cherries, and cacao, and have various physiological activities. It is reported that catechins have a health improvement effect and ameliorating effect against various diseases. In addition, antioxidant activity, liver damage prevention, cholesterol lowering effect, and anti-obesity activity were confirmed through in vivo animal and clinical studies. Although most diseases are reported as ones mediating various inflammations, the mechanism for improving inflammation remains unclear. Therefore, the current review article evaluates the physiological activity and various pharmacological actions of catechins and conclude by confirming an improvement effect on the inflammatory response.
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Scope: Vine tea (Ampelopsis grossedentata), a traditional Chinese tea, has displayed various biological activities. We aimed to investigate the effect of Vine Tea (Ampelopsis grossedentata) extract (VTE) on CCl4 -induced acute liver injury (ALI) in mice and to explore the underlying role of gut microbiota during the treatment. Methods and results: C57BL/6J mice injected with CCl4 were treated with VTE for 6 weeks. By using H&E staining, immunofluorescence staining, RT-PCR, and western blot, it was shown that VTE treatment significantly ameliorated hepatocyte necrosis, alleviated the mRNA levels of Tlr4, Il-6, iNOS, Acc1, and increased the mRNA levels of Ppar-γ and Hmg-coar compared to the CCl4 group. Also, VTE abrogated the decreased mRNA expressions of Zo-1, Occludin, and Mucin1 in colon tissues. Using microbial 16S rDNA sequencing, VTE treatment significantly downregulated the abundances of some harmful intestinal bacteria like Helicobacter and Oscillibacter. In contrast, VTE upregulated the contents of several beneficial bacteria, such as Ruminococcaceae_UCG-014 and Eubacterium_fissicatena_group. Further, VTE failed to improve ALI in the mice with gut microbiota depletion using antibiotic treatment. Conclusions: Our studies suggest that VTE exhibited a protective effect against CCl4 -induced ALI in mice by alleviating hepatic inflammation, suppressing intestinal epithelial barrier injury, and restoring gut microbiota dysbiosis. This article is protected by copyright. All rights reserved.
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Background: Green tea, obtained from the plant Camellis sinensis, is one of the oldest drinks in the world and contains numerous bioactive compounds. Studies have demonstrated the efficacy of green tea in preventing obesity and cardiovascular diseases that may be related to the reduction of lipid levels. Aim: This study aimed to evidence, through a systematic review, the therapeutic potential of green tea on the lipid profile in preclinical studies in obese animals and clinical studies in obese individuals. Methods: This systematic review follows the recommendations of the preferred report items for systematic reviews and meta-analyses. The electronic databases, PubMed (Medline), Science Direct, Scopus, and Web of Science were consulted. Articles from January 2009 to December 2019 were selected. Results: This search resulted in twenty-nine articles were included cirtically reviewed. In experimental studies, green tea administration has been shown to reduce total cholesterol, triglycerides and low-density lipoprotein cholesterol in animals exposed to obesity-inducing diet. In humans’ studies green tea was not shown to be effective for obese lipid control. Because supplementation with green tea extract reduced total cholesterol, triglycerides, low-density lipoprotein for three months at a specific dose. Conclusion: Therefore, green tea appears to act as a protective agent for dyslipidemia in obesity-induced animals. In human studies, green tea has not been shown to be effective in controlling obese lipids.
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Several DNA extraction methods have been reported for use with digesta or fecal samples, but problems are often encountered in terms of relatively low DNA yields and/or recovering DNA free of inhibitory substances. Here we report a modified method to extract PCR-quality microbial community DNA from these types of samples, which employs bead beating in the presence of high concentrations of sodium dodecyl sulfate (SDS), salt, and EDTA, and with subsequent DNA purification by QIA ® columns [referred to as repeated bead beating plus column (RBB+C) method]. The RBB+C method resulted in a 1.5- to 6-fold increase in DNA yield when compared to three other widely used methods. The community DNA prepared with the RBB+C method was also free of inhibitory substances and resulted in improved denaturing gradient gel electrophoresis (DGGE) profiles, which is indicative of a more complete lysis and representation of microbial diversity present in such samples.
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Metabolic disorders associated with obesity and cardiometabolic disorders are worldwide epidemic. Among the different environmental factors, the gut microbiota is now considered as a key player interfering with energy metabolism and host susceptibility to several non-communicable diseases. Among the next-generation beneficial microbes that have been identified, Akkermansia muciniphila is a promising candidate. Indeed, A. muciniphila is inversely associated with obesity, diabetes, cardiometabolic diseases and low-grade inflammation. Besides the numerous correlations observed, a large body of evidence has demonstrated the causal beneficial impact of this bacterium in a variety of preclinical models. Translating these exciting observations to human would be the next logic step and it now appears that several obstacles that would prevent the use of A. muciniphila administration in humans have been overcome. Moreover, several lines of evidence indicate that pasteurization of A. muciniphila not only increases its stability but more importantly increases its efficacy. This strongly positions A. muciniphila in the forefront of next-generation candidates for developing novel food or pharma supplements with beneficial effects. Finally, a specific protein present on the outer membrane of A. muciniphila, termed Amuc_1100, could be strong candidate for future drug development. In conclusion, as plants and its related knowledge, known as pharmacognosy, have been the source for designing drugs over the last century, we propose that microbes and microbiomegnosy, or knowledge of our gut microbiome, can become a novel source of future therapies.
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Human health is dependent upon the ability of the body to extract nutrients, fluids and oxygen from the external environment while at the same time, maintaining a state of internal sterility. Therefore, the cell layers that cover the surface areas of the body such as the lung, skin and gastrointestinal mucosa provide vital semi-permeable barriers which allow the transport of essential nutrients, fluid and waste products while at the same time keeping the internal compartments free of microbial organisms. These epithelial surfaces are highly specialized and differ in their anatomical structure depending on their location to provide appropriate and effective site-specific barrier function. Given this important role, it is not surprising that significant disease is often associated with alterations in epithelial barrier function. Examples of such diseases include inflammatory bowel disease (IBD)¹, chronic obstructive pulmonary disease (COPD)² and atopic dermatitis (AD)³. These chronic inflammatory disorders are often characterized by diminished tissue oxygen levels (hypoxia). Hypoxia triggers an adaptive transcriptional response governed by hypoxia inducible factors (HIFs), which are repressed by a family of oxygen-sensing HIF-hydroxylases. Here, we review recent evidence suggesting that pharmacologic hydroxylase inhibition may be of therapeutic benefit in IBD through the promotion of intestinal epithelial barrier function through both HIF-dependent and HIF-independent mechanisms.
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The trillions of microbes that exist in the gastrointestinal tract have emerged as pivotal regulators of mammalian development and physiology. Disruption of this gut microbiome, a process known as dysbiosis, causes or exacerbates various diseases, but whether gut dysbiosis affects recovery of neurological function or lesion pathology after traumatic spinal cord injury (SCI) is unknown. Data in this study show that SCI increases intestinal permeability and bacterial translocation from the gut. These changes are associated with immune cell activation in gut-associated lymphoid tissues (GALTs) and significant changes in the composition of both major and minor gut bacterial taxa. Postinjury changes in gut microbiota persist for at least one month and predict the magnitude of locomotor impairment. Experimental induction of gut dysbiosis in naive mice before SCI (e.g., via oral delivery of broad-spectrum antibiotics) exacerbates neurological impairment and spinal cord pathology after SCI. Conversely, feeding SCI mice commercial probiotics (VSL#3) enriched with lactic acid-producing bacteria triggers a protective immune response in GALTs and confers neuroprotection with improved locomotor recovery. Our data reveal a previously unknown role for the gut microbiota in influencing recovery of neurological function and neuropathology after SCI.
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Scope: Green tea has been known to confer numerous health benefits such as the prevention of cardiovascular disease, cancers, and obesity. Epigallocatechin-3-gallate (EGCG) is the major polyphenol present in green tea. Since EGCG is a food-derived component, intestinal epithelial cells (IECs) lining the gastrointestinal tract are constantly and directly exposed to EGCG. It is anticipated that EGCG can exert beneficial effects in the intestine. The aim of this study was to explore the protective effects of EGCG on intestinal barrier functions against bacterial translocation by using a porcine jejunal epithelial cell line, IPEC-J2. Methods and results: EGCG reduced bacterial translocation across IPEC-J2 cell monolayers through the enhancement of the intestinal epithelial immunological barrier function by inducing secretion of antimicrobial peptides, porcine β-defensins 1 and 2 (pBD-1 and 2), which possessed higher antimicrobial activity against Escherichia coli. Further mechanistic studies demonstrated that EGCG up-regulated pBD-2 but not pBD-1 via the p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Such effects were not an "artifact" of hydrogen peroxide (H2 O2 ), catechin dimers or other auto-oxidation products generated from EGCG in cell culture media. Conclusion: Our results imply that EGCG may be useful for prevention of intestinal disorders or bacterial infection in animals/humans. This article is protected by copyright. All rights reserved.
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Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestine. IBD is a multifactorial disorder, and IBD-associated genes are critical in innate immune response, inflammatory response, autophagy, and epithelial barrier integrity. Moreover, epithelial oxygen tension plays a critical role in intestinal inflammation and resolution in IBD. The intestines have a dynamic and rapid fluctuation in cellular oxygen tension, which is dysregulated in IBD. Intestinal epithelial cells have a steep oxygen gradient where the tips of the villi are hypoxic and the oxygenation increases at the base of the villi. IBD results in heightened hypoxia throughout the mucosa. Hypoxia signals through a well-conserved family of transcription factors, where hypoxia-inducible factor (HIF)-1α and HIF-2α are essential in maintaining intestinal homeostasis. In inflamed mucosa, HIF-1α increases barrier protective genes, elicits protective innate immune responses, and activates an antimicrobial response through the increase in β-defensins. HIF-2α is essential in maintaining an epithelial-elicited inflammatory response and the regenerative and proliferative capacity of the intestine following an acute injury. HIF-1α activation in colitis leads to a protective response, whereas chronic activation of HIF-2α increases the pro-inflammatory response, intestinal injury, and cancer. In this mini-review, we detail the role of HIF-1α and HIF-2α in intestinal inflammation and injury and therapeutic implications of targeting HIF signaling in IBD.
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Immune cell infiltration in (white) adipose tissue (AT) during obesity is associated with the development of insulin resistance. In AT, the main population of leukocytes are macrophages. Macrophages can be classified into two major populations: M1, classically activated macrophages, and M2, alternatively activated macrophages, although recent studies have identified a broad range of macrophage subsets. During obesity, AT M1 macrophage numbers increase and correlate with AT inflammation and insulin resistance. Upon activation, pro-inflammatory M1 macrophages induce aerobic glycolysis. By contrast, in lean humans and mice, the number of M2 macrophages predominates. M2 macrophages secrete anti-inflammatory cytokines and utilize oxidative metabolism to maintain AT homeostasis. Here, we review the immunologic and metabolic functions of AT macrophages and their different facets in obesity and the metabolic syndrome.
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Animals assemble and maintain a diverse but host-specific gut microbial community. In addition to characteristic microbial compositions along the longitudinal axis of the intestines, discrete bacterial communities form in microhabitats, such as the gut lumen, colonic mucus layers and colonic crypts. In this Review, we examine how the spatial distribution of symbiotic bacteria among physical niches in the gut affects the development and maintenance of a resilient microbial ecosystem. We consider novel hypotheses for how nutrient selection, immune activation and other mechanisms control the biogeography of bacteria in the gut, and we discuss the relevance of this spatial heterogeneity to health and disease.
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Available evidence on the bioactive, nutritional and putative detrimental properties of gut microbial metabolites has been evaluated to support a more integrated view of how prebiotics might affect host health throughout life. The present literature inventory targeted evidence for the physiological and nutritional effects of metabolites, for example, SCFA, the potential toxicity of other metabolites and attempted to determine normal concentration ranges. Furthermore, the biological relevance of more holistic approaches like faecal water toxicity assays and metabolomics and the limitations of faecal measurements were addressed. Existing literature indicates that protein fermentation metabolites (phenol, p -cresol, indole, ammonia), typically considered as potentially harmful, occur at concentration ranges in the colon such that no toxic effects are expected either locally or following systemic absorption. The endproducts of saccharolytic fermentation, SCFA, may have effects on colonic health, host physiology, immunity, lipid and protein metabolism and appetite control. However, measuring SCFA concentrations in faeces is insufficient to assess the dynamic processes of their nutrikinetics. Existing literature on the usefulness of faecal water toxicity measures as indicators of cancer risk seems limited. In conclusion, at present there is insufficient evidence to use changes in faecal bacterial metabolite concentrations as markers of prebiotic effectiveness. Integration of results from metabolomics and metagenomics holds promise for understanding the health implications of prebiotic microbiome modulation but adequate tools for data integration and interpretation are currently lacking. Similarly, studies measuring metabolite fluxes in different body compartments to provide a more accurate picture of their nutrikinetics are needed.
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Toll-like receptors (TLRs) belong to the pattern recognition receptor (PRR) family, a key component of the innate immune system. TLRs detect invading pathogens and initiate an immediate immune response to them, followed by a long-lasting adaptive immune response. Activation of TLRs leads to the synthesis of pro-inflammatory cytokines and chemokines and the expression of co-stimulatory molecules. TLR4 specifically recognizes bacterial lipopolysaccharide, along with several other components of pathogens and endogenous molecules produced during abnormal situations, such as tissue damage. Evolution across species can lead to substantial diversity in the TLR4's affinity and specificity to its ligands, the TLR4 gene and cellular expression patterns and tissue distribution. Consequently, TLR4 functions vary across different species. In recent years, the use of synthetic TLR agonists as adjuvants has emerged as a realistic therapeutic goal, notably for the development of vaccines against poorly immunogenic targets. Given that an adjuvanted vaccine must be assessed in pre-clinical animal models before being tested in humans, the extent to which an animal model represents and predicts the human condition is of particular importance. This review focuses on the current knowledge on the critical points of divergence between human and the mammalian species commonly used in vaccine research and development (non-human primate, mouse, rat, rabbit, swine, and dog), in terms of molecular, cellular, and functional properties of TLR4.
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Background: In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. Methods: We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). Findings: Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. Interpretation: Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. Funding: Bill & Melinda Gates Foundation.
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Sex hormones strongly influence body fat distribution and adipocyte differentiation. Estrogens and testosterone differentially affect adipocyte physiology, but the importance of estrogens in the development of metabolic diseases during menopause is disputed. Estrogens and estrogen receptors regulate various aspects of glucose and lipid metabolism. Disturbances of this metabolic signal lead to the development of metabolic syndrome and a higher cardiovascular risk in women. The absence of estrogens is a clue factor in the onset of cardiovascular disease during the menopausal period, which is characterized by lipid profile variations and predominant abdominal fat accumulation. However, influence of the absence of these hormones and its relationship to higher obesity in women during menopause are not clear. This systematic review discusses of the role of estrogens and estrogen receptors in adipocyte differentiation, and its control by the central nervous systemn and the possible role of estrogen-like compounds and endocrine disruptors chemicals are discussed. Finally, the interaction between the decrease in estrogen secretion and the prevalence of obesity in menopausal women is examined. We will consider if the absence of estrogens have a significant effect of obesity in menopausal women.
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Our understanding of the microbial involvement in inflammatory bowel disease (IBD) pathogenesis has increased exponentially over the past decade. The development of newer molecular tools for the global assessment of the gut microbiome and the identification of nucleotide-binding oligomerization domain-containing protein 2 in 2001 and other susceptibility genes for Crohn's disease in particular has led to better understanding of the aetiopathogenesis of IBD. The microbial studies have elaborated the normal composition of the gut microbiome and its perturbations in the setting of IBD. This altered microbiome or "dysbiosis" is a key player in the protracted course of inflammation in IBD. Numerous genome-wide association studies have identified further genes involved in gastrointestinal innate immunity (including polymorphisms in genes involved in autophagy: ATG16L1 and IGRM), which have helped elucidate the relationship of the local innate immunity with the adjacent luminal bacteria. These developments have also spurred the search for specific pathogens which may have a role in the metamorphosis of the gut microbiome from a symbiotic entity to a putative pathogenic one. Here we review advances in our understanding of microbial involvement in IBD pathogenesis over the past 10 years and offer insight into how this will shape our therapeutic management of the disease in the coming years.
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TLR4 is the main recognition receptor of bacterial lipopolysaccharides, which play an important role in innate and adaptive immunity. We used real-time PCR to analyze the tissue expression profile and differential expression of TLR4 in 4 pig populations (Escherichia coli F18-resistant Sutai, E. coli F18-sensitive Sutai, Large White, Meishan), in order to determine the role that the TLR4 gene plays in resistance to E. coli F18. We found that TLR4 expressed consistently in the 4 populations, with relatively high levels in immune tissues and the highest level in the lung. Generally, the expression of TLR4 in E. coli F18-sensitive individuals was the highest, followed by that in E. coli F18-resistant, Large White and Meishan. In the spleen, lung, kidney, lymph nodes, and thymus gland, TLR4 expression is significantly higher in the E. coli F18-sensitive than in the other 3 populations; there were no significant differences among E. coli F18-resistant Sutai, Large White, and Meishan. In addition, Gene Ontology and pathway analysis showed that TLR4 takes part in the inflammatory response. We found that porcine TLR4 has consistent tissue specificity in each breed, and downregulation of expression of the TLR4 gene is related to resistance to E. coli F18 in weaning piglets.
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Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community's functional capabilities. Here we describe PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this 'predictive metagenomic' approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.
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Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
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Antimicrobial peptides are secreted by the intestinal epithelium to defend from microbial threats. The role of human β defensin-1 (hBD-1) is notable because its gene (beta-defensin 1 (DEFB1)) is constitutively expressed and its antimicrobial activity is potentiated in the low-oxygen environment that characterizes the intestinal mucosa. Hypoxia-inducible factor (HIF) is stabilized even in healthy intestinal mucosa, and we identified that epithelial HIF-1α maintains expression of murine defensins. Extension to a human model revealed that basal HIF-1α is critical for the constitutive expression of hBD-1. Chromatin immunoprecipitation identified HIF-1α binding to a hypoxia response element in the DEFB1 promoter whose importance was confirmed by site-directed mutagenesis. We used 94 human intestinal samples to identify a strong expression correlation between DEFB1 and the canonical HIF-1α target GLUT1. These findings indicate that basal HIF-1α is critical for constitutive expression of enteric DEFB1 and support targeting epithelial HIF for restoration and maintenance of intestinal integrity.Mucosal Immunology advance online publication 6 March 2013; doi:10.1038/mi.2013.6.
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The aim of this study was to evaluate the effects of green tea Camellia sinensis extract on proinflammatory molecules and lipolytic protein levels in adipose tissue of diet-induced obese mice. Animals were randomized into four groups: CW (chow diet and water); CG (chow diet and water + green tea extract); HW (high-fat diet and water); HG (high-fat diet and water + green tea extract). The mice were fed ad libitum with chow or high-fat diet and concomitantly supplemented (oral gavage) with 400 mg/kg body weight/day of green tea extract (CG and HG, resp.). The treatments were performed for eight weeks. UPLC showed that in 10 mg/mL green tea extract, there were 15 μg/mg epigallocatechin, 95 μg/mg epigallocatechin gallate, 20.8 μg/mg epicatechin gallate, and 4.9 μg/mg gallocatechin gallate. Green tea administered concomitantly with a high-fat diet increased HSL, ABHD5, and perilipin in mesenteric adipose tissue, and this was associated with reduced body weight and adipose tissue gain. Further, we observed that green tea supplementation reduced inflammatory cytokine TNFα levels, as well as TLR4, MYD88, and TRAF6 proinflammatory signalling. Our results show that green tea increases the lipolytic pathway and reduces adipose tissue, and this may explain the attenuation of low-grade inflammation in obese mice.
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BACKGROUND #ENTITYSTARTX00026; While it is widely accepted that obesity is associated with low-grade systemic inflammation, the molecular origin of the inflammation remains unknown. Here, we investigated the effect of endotoxin-induced inflammation via TLR4 signaling pathway at both systemic and intestinal levels in response to a high-fat diet. C57BL/6J and TLR4-deficient C57BL/10ScNJ mice were maintained on a low-fat (10 kcal % fat) diet (LFD) or a high-fat (60 kcal % fat) diet (HFD) for 8 weeks. HFD induced macrophage infiltration and inflammation in the adipose tissue, as well as an increase in the circulating proinflammatory cytokines. HFD increased both plasma and fecal endotoxin levels and resulted in dysregulation of the gut microbiota by increasing the Firmicutes to Bacteriodetes ratio. HFD induced the growth of Enterobecteriaceae and the production of endotoxin in vitro. Furthermore, HFD induced colonic inflammation, including the increased expression of proinflammatory cytokines, the induction of Toll-like receptor 4 (TLR4), iNOS, COX-2, and the activation of NF-κB in the colon. HFD reduced the expression of tight junction-associated proteins claudin-1 and occludin in the colon. HFD mice demonstrated higher levels of Akt and FOXO3 phosphorylation in the colon compared to the LFD mice. While the body weight of HFD-fed mice was significantly increased in both TLR4-deficient and wild type mice, the epididymal fat weight and plasma endotoxin level of HFD-fed TLR4-deficient mice were 69% and 18% of HFD-fed wild type mice, respectively. Furthermore, HFD did not increase the proinflammatory cytokine levels in TLR4-deficient mice. HFD induces inflammation by increasing endotoxin levels in the intestinal lumen as well as in the plasma by altering the gut microbiota composition and increasing its intestinal permeability through the induction of TLR4, thereby accelerating obesity.
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