Nonextractable Polyphenols from Fu Brick Tea Alleviates Ulcerative Colitis by Controlling Colon Microbiota-Targeted Release to Inhibit Intestinal Inflammation in Mice.

This study was designed to elucidate the colon microbiota-targeted release of nonextractable bound polyphenols (NEPs) derived from Fu brick tea and to further identify the possible anti-inflammatory mechanism in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. 1.5% DSS drinking water-induced C57BL/6J mice were fed rodent chow supplemented with or without 8% NEPs or dietary fibers (DFs) for 37 days. The bound p-hydroxybenzoic acid and quercetin in NEPs were liberated up to 590.5 ± 70.6 and 470.5 ± 51.6 mg/g by in vitro human gut microbiota-simulated fermentation, and released into the colon of the mice supplemented with NEPs by 4.4- and 1.5-fold higher than that of the mice supplemented without NEPs, respectively (p < 0.05). Supplementation with NEPs also enhanced the colonic microbiota-dependent production of SCFAs in vitro and in vivo (p < 0.05). Interestingly, Ingestion of NEPs in DSS-induced mice altered the gut microbiota composition, reflected by a dramatic increase in the relative abundance of Dubosiella and Enterorhabdus and a decrease in the relative abundance of Alistipes and Romboutsia (p < 0.05). Consumption of NEPs was demonstrated to be more effective in alleviating colonic inflammation and UC symptoms than DFs alone in DSS-treated mice (p < 0.05), in which the protective effects of NEPs against UC were highly correlated with the reconstruction of the gut microbiome, formation of SCFAs, and release of bound polyphenols. These findings suggest that NEPs as macromolecular carriers exhibit targeted delivery of bound polyphenols into the mouse colon to regulate gut microbiota and alleviate inflammation.

Effects of Fu brick tea polysaccharides on gut microbiota and fecal metabolites of HFD/STZ-induced type 2 diabetes rats.

The prevalence of type 2 diabetes mellitus (T2DM) has dramatically increased globally, and the antidiabetic effects and underlying mechanisms of the polysaccharides extracted from Fu brick tea (FBTP) were investigated in high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM rats. Administration of FBTP at 200 and 400 mg per kg bw significantly relieved dyslipidemia (i.e. TC, TG, LDL-C and HDL-C), insulin resistance (IR) and pancreas oxidative stress (i.e. CAT and GSH-Px) in T2DM rats. Mechanistically, FBTP rescued the HFD/STZ-induced alterations in the abundance of Bacteroidota, Actinobacteriota, Proteobacteria and Firmicutes. At the genus level, FBTP notably increased the abundance of Ruminococcus, Lactobacillus and Lachnospiraece_NK4A136_group, but reduced the population of Prevotella and Faecalibaculum in T2DM rats. FBTP also significantly elevated colonic short-chain fatty acid (SCFAs) levels. Moreover, apparent changes in amino acid absorption and metabolism were observed upon FBTP intervention. These findings suggested that FBTP might alleviate T2DM by reshaping the gut microbiota and regulating intestinal metabolites.

Polysaccharide from Ziyang Selenium-Enriched Green Tea Prevents Obesity and Promotes Adipose Thermogenesis via Modulating the Gut Microbiota.

The objective of the current study was to explore the potential mechanism of Ziyang selenium-enriched green tea polysaccharide (Se-GTP) against obesity. The results showed that Se-GTP significantly alleviated obesity and related metabolic disorders caused by high-fat diet (HFD) in mice. 16S rRNA gene sequencing results revealed that Se-GTP improved gut microbiota disturbance of obese mice and facilitated proliferation of probiotics such as Bacteroides, Bifidobacterium, Lactobacillus, and Akkermansia. In addition, the colonic content of succinate, a product of microbial metabolite in connection with adipocyte thermogenesis, was significantly enhanced by Se-GTP treatment. Therefore, Se-GTP facilitated brown adipose tissue (BAT) thermogenesis and inguinal white adipose tissue (iWAT) browning in obese mice, which could be revealed by increased expressions of thermogenic marker proteins UCP1, PGC-1α, and CIDEA in BAT and iWAT. Interestingly, Se-GTP intervention also observably increased the content of M2-like macrophages in iWAT of obese mice. To summarize, the results of this study are the first to show that Se-GTP can stimulate the browning of iWAT and BAT thermogenesis to counteract obesity, which may be pertinent with the alteration of gut microbiota in obese mice.

Fu Brick Tea Alleviates Constipation via Regulating the Aquaporins-Mediated Water Transport System in Association with Gut Microbiota.

This study aimed to investigate the amendatory effects of Fu brick tea aqueous extract (FTE) on constipation and its underlying molecular mechanism. The administration of FTE by oral gavage (100 and 400 mg/kg·bw) for 5 weeks significantly increased fecal water content, improved difficult defecation, and enhanced intestinal propulsion in loperamide (LOP)-induced constipated mice. FTE also reduced colonic inflammatory factors, maintained the intestinal tight junction structure, and inhibited colonic Aquaporins (AQPs) expression, thus normalizing the intestinal barrier and colonic water transport system of constipated mice. 16S rRNA gene sequence analysis results indicated that two doses of FTE increased the Firmicutes/Bacteroidota (F/B) ratio at the phylum level and increased the relative abundance of Lactobacillus from 5.6 ± 1.3 to 21.5 ± 3.4% and 28.5 ± 4.3% at the genus level, subsequently resulting in a significant elevation of colonic contents short-chain fatty acids levels. The metabolomic analysis demonstrated that FTE improved levels of 25 metabolites associated with constipation. These findings suggest that Fu brick tea has the potential to alleviate constipation by regulating gut microbiota and its metabolites, thereby improving the intestinal barrier and AQPs-mediated water transport system in mice.

Theabrownin from Fu Brick Tea Improves Ulcerative Colitis by Shaping the Gut Microbiota and Modulating the Tryptophan Metabolism.

Fu brick tea theabrownin (FBTB) is a kind of biomacromolecule produced by oxidative polymerization of tea polyphenols. Although a variety of diseases can be alleviated by TB, its ability to treat ulcerative colitis (UC) is still worth exploring. A dextran sulfate sodium (DSS)-induced chronic UC mouse model was designed to first explore the alleviatory effect of FBTB on UC and its underlying mechanism by the sequencing of fecal 16S rRNA genes, metabolomics, and fecal microbiota transplantation (FMT). Administration of FBTB at 400 mg/kg bw in DSS-damaged mice could effectively reduce colonic damage and inflammation and improve colonic antioxidant capacity to relieve the UC-caused symptoms. FBTB could correct the disrupted gut microbiota caused by UC and contribute to the proliferation of Lactobacillus and Parasutterella. FMT in combination with antibiotic treatment showed that FBTB could elevate the levels of microbial tryptophan metabolites, including indole-3-acetaldehyde (IAld) and indole-3-acetic acid (IAA), by selectively promoting the growth of Lactobacillus. Importantly, FBTB-elevated IAld and IAA could activate aromatic hydrocarbon receptors (AhRs) and enhance interleukin-22 production to repair the intestinal barrier. These findings demonstrated that FBTB alleviated UC mainly by targeting the gut microbiota involved in the AhR pathway for prophylactic and therapeutic treatment of UC.

Effects of sheep whey protein combined with Fu brick tea polysaccharides and stachyose on immune function and intestinal metabolites of cyclophosphamide-treated mice.

BACKGROUND: Sheep whey protein (SWP), Fu brick tea polysaccharides (FBTP) and stachyose (STA) have been shown to improve immunity, but little is known about the regulatory effect of SWP, FBTP, STA and their combined formula (CF) on immune function and intestinal metabolism of immunosuppressed mice induced by cyclophosphamide (CTX). RESULTS: Administration of SWP, FBTP, STA or CF restored the levels of body weight, immune organ index, immune organ morphology, cytokines and immunoglobulins in CTX immunosuppressed mice. Interestingly, CF improved all the mentioned parameters more effective than administration of SWP, FBTP or STA alone. In addition, CF was more effective to increase the levels of intestinal immune-related gene expression than FBTP, SWP or STA alone in immunosuppressed mice, suggesting that CF exhibited excellent intestinal immune regulation function. CF also significantly improved cecal concentrations of short-chain fatty acids of CTX-treated mice. Furthermore, metabolomics analysis demonstrated that CF recovered the levels of 28 metabolites associated with the CTX treatment to the levels of normal mice. CONCLUSION: Conclusively, these findings suggested that CF as a functional food combination of SWP, FBTP and STA could promote the immune function against human diseases, which providing theoretical support for the co-ingestion of SWP and functional sugars as a feasible strategy for improving the body immunity in the future. © 2023 Society of Chemical Industry.

Gut Bacterial Indole-3-acetic Acid Induced Immune Promotion Mediates Preventive Effects of Fu Brick Tea Polyphenols on Experimental Colitis.

Ulcerative colitis has been consistently associated with gut microbiota imbalance and disturbed immune system. Emerging research suggests a protective function of polyphenols on prevention and treatment of ulcerative colitis, yet underlying mechanisms remain unclear. Fu brick tea, a postfermented tea, contains abundant polyphenols with anti-inflammatory and antioxidant properties. In the present study, we found that prophylactic supplementation of polyphenols extracted from Fu brick tea (FBTP) dose-dependently alleviated colitis symptoms, immune cells infiltration, and pro-inflammatory cytokines secretion in mice suffering dextran sulfate sodium induced murine colitis. FBTP substantially reshaped gut microbiota and promoted microbial transformation of tryptophan into indole-3-acetic acid (I3A), thereafter leading to aryl hydrocarbon receptor (AHR)-mediated protection from colitis through enhanced expressions of IL-22 and tight junction proteins (i.e., ZO-1, occluding and claudin-1) in colon. Multiomics integration analyses revealed strong connections between I3A, tryptophan-metabolizing bacteria, AHR activity, and pathological phenotypes of colitis. Notably, FBTP failed to significantly alleviate colitis symptoms in the absence of gut microbiota, while intragastric administration of I3A could imitate benefits of FBTP on colitis alleviation and intestinal epithelial homeostasis through a direct enhancement in AHR activity in microbiota-depleted mice. These findings further determine the key role of gut microbiota controlled I3A-AHR signaling in mediating the FBTP on colitis alleviation. This study provides the first data proposing the FBTP as a natural prebiotic for colitis alleviation through the gut microbiota-dependent modulation of the AHR pathway. Most importantly, we also identified I3A as a key microbial metabolite targeted by FBTP for exhibiting health-promoting effects.

Detrimental Role of PDZ-RhoGEF in Pathological Cardiac Hypertrophy.

BACKGROUND: Postsynaptic density 95/disk-large/ZO-1 Rho guanine nucleotide exchange factor (PDZ-RhoGEF, PRG) functions as a RhoGEF for activated Gα13 and transmits activation signals to downstream signaling pathways in various pathological processes. Although the prohypertrophic effect of activated Gα13 (guanine nucleotide binding protein alpha 13; a heterotrimeric G protein) is well-established, the role of PDZ-RhoGEF in pathological cardiac hypertrophy is still obscure. METHODS: Genetically engineered mice and neonatal rat ventricular myocytes were generated to investigate the function of PRG in pathological myocardial hypertrophy. The prohypertrophic stimuli-induced alternations in the morphology and intracellular signaling were measured in myocardium and neonatal rat ventricular myocytes. Furthermore, multiple molecular methodologies were used to identify the precise molecular mechanisms underlying PDZ-RhoGEF function. RESULTS: Increased PDZ-RhoGEF expression was documented in both hypertrophied hearts and neonatal rat ventricular myocytes. Upon prohypertrophic stimuli, the PDZ-RhoGEF-deficient hearts displayed alleviated cardiomyocyte enlargement and attenuated collagen deposition with improved cardiac function, whereas the adverse hypertrophic responses in hearts and neonatal rat ventricular myocytes were markedly exaggerated by PDZ-RhoGEF overexpression. Mechanistically, RhoA (ras homolog family member A)-dependent signaling pathways may function as the downstream effectors of PDZ-RhoGEF in hypertrophic remodeling, as confirmed by rescue experiments using a RhoA inhibitor and dominant-negative RhoA. Furthermore, PDZ-RhoGEF is associated with activated Gα13 and contributes to Gα13-mediated activation of RhoA-dependent signaling. CONCLUSIONS: Our data provide the first evidence that PDZ-RhoGEF promotes pathological cardiac hypertrophy by linking activated Gα13 to RhoA-dependent signaling pathways. Therefore, PDZ-RhoGEF has the potential to be a diagnostic marker or therapeutic target for pathological cardiac hypertrophy.

Response of gut microbiota and ileal transcriptome to inulin intervention in HFD induced obese mice.

Inulin, as a dietary fiber, exerted prominent anti-obesity effects by modulating gut microbiota. However, the possible relationship and interplay of gut microbiome and function of distal intestine is still unclear now. This study aimed to investigate the possible targets of microbes and the related intestinal genes mediated by inulin. C57 BL/6 male mice were randomly allocated to chow diet (Chow) group, high-fat diet (HFD) group, and HFD supplemented with 3 % inulin (Inulin) group. Compared with HFD treatment, inulin supplementation significantly decreased the body weight, fat deposition, and fasting blood glucose level. In addition, mice treated with inulin had a remarkable alteration in the structure of cecal microbiota and transcriptomic profiling of ileum. In particular, inulin supplementation significantly reversed the HFD induced expression of Bacteroides, Allobaculum and nonrank_f_Bacteroidates_S24-7_group, and reversed the expression of genes belonging to phospholipase A2 (PLA2) family and cytochrome P450 (CYP450) family. In summary, inulin might alleviate HFD-induced fat deposition and metabolic disorders via regulating lipid metabolism of ileum, while the interaction between the sPLA2s and gut microbes might play important roles in the process.

Eurotium cristatum Exhibited Anti-Colitis Effects via Modulating Gut Microbiota-Dependent Tryptophan Metabolism.

Fu-brick tea (FBT) has attracted the attention of researchers because of its unique nutritional value, but it remains unknown whether Eurotium cristatum, the critical fungus from FBT, is responsible for the observed anti-colitis effects of FBT. Herein, the effects of E. cristatum on dextran sulfate sodium (DSS)-induced ulcerative colitis was first discussed. The results illustrated that the oral administration of E. cristatum inhibited DSS-induced colon damage. Microbiota analysis revealed that E. cristatum improved the intestinal homeostasis of colitis mice, especially increased the proportion of Lactobacillus, followed by an obvious increase in fecal short-chain fatty acids (SCFAs). Besides, E. cristatum markedly promoted tryptophan metabolism and increased the fecal contents of tryptophan metabolites in colitis mice. Furthermore, E. cristatum drastically increased the content of colonic IL-22 and the expression of tight-junction proteins. Conclusively, these results suggest that E. cristatum can resist colon damage and other implications of colitis by regulating the microbiota and enhancing tryptophan metabolism to strengthen intestinal barriers.

Dietary Turmeric Consumption Alleviates Ulcerative Colitis via Restoring Tryptophan Metabolism and Alleviating Gut Microbiota Dysbiosis in Mice.

This study was designed to first verify the protective capacity of turmeric powder (TP) as a traditional cooking spice against dextran sulfate sodium (DSS)-induced intestinal inflammation and intestine microbiota imbalance. The DSS-induced mice were fed a standard rodent chow supplemented with or without TP (8%) for 37 days. The results indicated that the pathological phenotype, gut barrier disruption, and colon inflammation of DSS-induced mice were significantly improved through supplementation of TP. In addition, 16S rRNA-based microbiota or targeted metabolomics analysis indicated that TP ameliorated intestinal microbiota dysbiosis caused by DSS and particularly enhanced the abundances of probiotics correlated with tryptophan metabolism, such as Lactobacillus and Bifidobacterium, where the cecal tryptophan was metabolized to indole-3-propionic acid and indole-3-acetic acid. Consumption of TP markedly enhanced the expression levels of colonic aromatic hydrocarbon receptors and further increased the expressions of intestinal tight junction proteins and interleukin-22 in the colitis mice. Collectively, these findings manifest the protective actions of dietary TP consumption against ulcerative colitis via restoring the intestinal microbiota disorders, promoting microbial metabolism, and improving intestinal barrier damage.

Caloric Restriction, Friend or Foe: Effects on Metabolic Status in Association with the Intestinal Microbiome and Metabolome.

Daily calorie restriction (CR) has shown benefits on weight loss and alleviation of metabolic disorders. We investigated the effects of three CR regimens, i.e., 20% (CR-20), 40% (CR-40), and 60% (CR-60) less than the average daily calorie intake, respectively, on the metabolic parameters, gut microbiome composition, and its related metabolites in healthy mice. Compared with mice fed ad libitum (AL), CR dose-dependently reduced the body weight, and weights of liver and epididymal adipose tissues, and enhanced the insulin sensitivity, glucose tolerance, and lipid homeostasis. Moreover, expression levels of intestinal tight junction proteins (i.e., ZO-1, claudin, and occludin) were significantly promoted by CR than those of AL mice, demonstrating the CR-induced improvement of the intestinal barrier integrity. CR contributed to the enrichment of beneficial microbiota (e.g., Lactobacillus, Bacteroides, and Akkermansia) and increased propionic acid levels. Notably, CR-60 deleteriously caused liver injury, and enhanced hepatic inflammatory cytokines (i.e., IL-1, IL-6, and TNF-α) and lipopolysaccharides, which were accompanied by high levels of trimethylamine (TMA) and trimethylamine oxide (TMAO) in relation to CR-60-altered gut microbiota structure and fecal metabolome. Additionally, we found differential impacts of CR-20, -40, or -60 on amino acid absorption and metabolism. Our findings support the health-promoting benefits of 60-80% daily calorie intake on the metabolic status by regulating the gut microbiota in healthy mice. However, excessive CR caused liver injury and gut microbiota-dependent elevation of TMAO. The differential effects of CR regimens on the intestinal microbiome and fecal metabolome provide novel insights into the dietary pattern-gut microbiome interactions linked with host metabolism.

Role of collateral flow in infarct border zone extent and contractile function in patients with chronic coronary total occlusion.

PURPOSE: There is a paucity of data regarding the border zone parameters in patients with chronic coronary total occlusion (CTO). We investigated the border zone extent and contractile function and their associations with collateral flow. METHODS: CTO patients (n = 47) and sex- and age-matched volunteers (n = 15) were prospectively enrolled and underwent cardiac MRI examinations to acquire cine and late-gadolinium enhancement (LGE) images. Myocardial peak strain (PS) and the time to PS were determined at the segmental level and global level. Infarct, border zone, adjacent, and remote regions were defined according to the transmural extent of infarction (TEI) by LGE at each segment. Angiographic collateral flow was evaluated using the Rentrop grading system. RESULTS: CTO patients with well-developed collateral flow had a higher TEI in border zone regions compared to patients with poorly developed collateral flow (p = 0.02). Conversely, CTO patients with poorly developed collaterals showed a higher TEI in infarct regions (p < 0.01). Enhanced border function, characterized by greater PS and earlier time to PS, was noted in well-developed collaterals (all p < 0.05). In the multivariate linear analyses, the level of collateral flow was an independent predictor of the border zone extent (ß = 0.40, p = 0.02) and contractile function (radial: ß = -0.42, p = 0.02; circumferential: ß = 0.39, p = 0.02; and longitudinal: ß = 0.47, p < 0.01). CONCLUSIONS: In CTO patients, the presence of well-developed collateral flow was closely linked to a greater extent of LGE and contractile function in border zone regions. Our findings shed light on the cardiac MRI-based pathophysiological underpinning in border zone regions, which could offer complementary and prognostic information in clinical practice.

Artemisia sphaerocephala Krasch polysaccharide promotes adipose thermogenesis and decreases obesity by shaping the gut microbiota.

This study was designed to investigate the underlying mechanism of Artemisia sphaerocephala Krasch polysaccharide (ASKP) against obesity. Here, our results showed that ASKP considerably reduced body weight gain and metabolic disorders in high fat diet (HFD)-fed mice. 16S rRNA gene sequencing revealed that ASKP relieved the gut microbiota disorder caused by HFD and promoted the proliferation of probiotics such as Lactobacillus, Bifidobacterium and Blautia. Interestingly, the fecal levels of succinate, a microbial metabolite associated with adipose thermogenesis, were dramatically elevated by ASKP treatment in obese mice. Accordingly, ASKP promoted thermogenesis of brown adipose tissue (BAT) and browning of inguinal white adipose tissue (iWAT) of mice fed with a HFD, as revealed by the elevated expression of thermogenic marker genes (UCP1, CIDEA and PGC1α) in BAT and iWAT. Importantly, antibiotic treatment significantly decreased the ASKP-elevated fecal levels of succinate and further abolished the adipose thermogenesis effects of ASKP. Taken together, our results show that ASKP prevents obesity through iWAT browning and BAT activation, a mechanism that is dependent on the gut microbiota metabolism.

Fu brick tea alleviates alcoholic liver injury by modulating the gut microbiota-liver axis and inhibiting the hepatic TLR4/NF-κB signaling pathway.

This study first evaluated the protective effects of Fu brick tea water extracts (FTE) on alcoholic liver injury and its underlying mechanism in C57BL/6J mice. Oral administration of FTE by oral gavage (400 mg per kg bw) for 12 weeks significantly alleviated lipid metabolism disorder, reduced the activities of serum ALT and AST, decreased the expression of the liver CYP2E1 gene, and enhanced the antioxidant capacities of the livers in alcohol-fed mice (p < 0.05). FTE also relieved alcohol-induced gut microbiota dysbiosis by promoting the proliferation of probiotics such as Muribaculaceae and Lactobacillus, and subsequently increased the cecal levels of short-chain fatty acids (SCFAs) and decreased the tryptophan content of alcohol-fed mice (p < 0.05). Importantly, FTE was found to improve the alcohol-impaired gut barrier function by up-regulating the expression of the epithelial tight junction protein. Accordingly, FTE decreased the circulating lipopolysaccharide (LPS) and thus inhibited the hepatic TLR4/NF-κB signaling pathway to ameliorate alcoholic liver injury. Cumulatively, these findings shed light on the important role of the gut microbiota-liver axis behind the protective efficacy of FTE on alcoholic liver injury.

Eurotium cristatum reduces obesity by alleviating gut microbiota dysbiosis and modulating lipid and energy metabolism.

BACKGROUND: Fuzhuan brick tea (FBT) has been shown to prevent obesity, but little is known about the effect of Eurotium cristatum, a critical fungus from FBT. This study examined the effects of live E. cristatum on lipid metabolism and gut microbiota composition in high-fat (HF) diet-induced obese mice. RESULTS: Male HF diet-fed mice were treated with E. cristatum for 12 weeks. The results showed that E. cristatum administration caused strong inhibition against HF-induced body weight gain, dyslipidemia and liver oxidative stress damage. Additionally, Firmicutes and Bacteroidetes in phylum level and six types of bacterial including short-chain fatty acids (SCFAs) producing bacteria in genus level were found to be significantly changed in E. cristatum treated mice as compared to HF fed mice. As expected, E. cristatum could increase total SCFAs levels in feces. Interestingly, E. cristatum markedly increased the proportion of Akkermansia to resist obesity. Functional prediction analysis indicated that E. cristatum changed lipid and energy metabolism. Furthermore, E. cristatum ingestion can modulate hepatic acetyl-coa carboxylase (ACC), fatty acid synthase (FAS), sterol-regulatory element binding protein-1 (SREBP-1) and adipose uncoupling protein-1 (UCP-1) expression. CONCLUSION: Conclusively, these findings suggest that E. cristatum can prevent the HF-induced lipid accumulation and other complications by modulating gut microbiota, lipid and energy metabolism. © 2022 Society of Chemical Industry.

Fu Brick Tea Manages HFD/STZ-Induced Type 2 Diabetes by Regulating the Gut Microbiota and Activating the IRS1/PI3K/Akt Signaling Pathway.

The antidiabetic effects of Fu brick tea aqueous extract (FTE) and its underlying molecular mechanism in type 2 diabetes mellitus (T2DM) mice were investigated. FTE treatment significantly relieved dyslipidemia, insulin resistance (IR), and hepatic oxidative stress caused by T2DM. FTE also ameliorated the T2DM-induced gut dysbiosis by decreasing the Firmicutes/Bacteroidota (F/B) ratio at the phylum level and promoting the proliferation of Bifidobacterium, Parabacteroides, and Roseburia at the genus level. Besides, FTE significantly improved colonic short-chain fatty acid levels of T2DM mice. Furthermore, the antidiabetic effects of FTE were proved to be mediated by the IRS1/PI3K/Akt and AMPK-mediated gluconeogenesis signaling pathways. Metabolomics analysis illustrated that FTE recovered the levels of 28 metabolites associated with T2DM to the levels of normal mice. Taken together, these findings suggest that FTE can alleviate T2DM by reshaping the gut microbiota, activating the IRS1/PI3K/Akt pathway, and regulating intestinal metabolites.

Intramyocardial Hemorrhage and the "Wave Front" of Reperfusion Injury Compromising Myocardial Salvage.

BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) is lifesaving. However, the benefit of reperfusion therapy can be paradoxically diminished by reperfusion injury, which can increase MI size. OBJECTIVES: Hemorrhage is known to occur in reperfused MIs, but whether hemorrhage plays a role in reperfusion-mediated MI expansion is not known. METHODS: We studied cardiac troponin kinetics (cTn) of ST-segment elevation MI patients (n = 70) classified by cardiovascular magnetic resonance to be hemorrhagic (70%) or nonhemorrhagic following primary percutaneous coronary intervention. To isolate the effects of hemorrhage from ischemic burden, we performed controlled canine studies (n = 25), and serially followed both cTn and MI size with time-lapse imaging. RESULTS: CTn was not different before reperfusion; however, an increase in cTn following primary percutaneous coronary intervention peaked earlier (12 hours vs 24 hours; P < 0.05) and was significantly higher in patients with hemorrhage (P < 0.01). In hemorrhagic animals, reperfusion led to rapid expansion of myocardial necrosis culminating in epicardial involvement, which was not present in nonhemorrhagic cases (P < 0.001). MI size and salvage were not different at 1 hour postreperfusion in animals with and without hemorrhage (P = 0.65). However, within 72 hours of reperfusion, a 4-fold greater loss in salvageable myocardium was evident in hemorrhagic MIs (P < 0.001). This paralleled observations in patients with larger MIs occurring in hemorrhagic cases (P < 0.01). CONCLUSIONS: Myocardial hemorrhage is a determinant of MI size. It drives MI expansion after reperfusion and compromises myocardial salvage. This introduces a clinical role of hemorrhage in acute care management, risk assessment, and future therapeutics.

Gut microbiota-dependent catabolites of tryptophan play a predominant role in the protective effects of turmeric polysaccharides against DSS-induced ulcerative colitis.

Gut barrier dysfunction is triggered by gut microbiota dysbiosis that is closely associated with ulcerative colitis. Recently, more attention has been devoted to the ability of the non-digestively colon-targeted plant polysaccharides to regulate the function and composition of the intestinal microbiota. Here, we first studied the prophylactic capacity of turmeric polysaccharides (TPS) to ameliorate dextran sulfate sodium (DSS)-induced gut microbiota imbalance. The results revealed that TPS administration could greatly improve the pathological phenotype, gut barrier disruption and colon inflammation in colitis mice. Besides, targeted metabolomics or 16S rRNA-based microbiota analysis demonstrated that TPS alleviated gut microbiota dysbiosis caused by DSS, especially increasing the abundance of probiotics associated with tryptophan metabolism, such as Lactobacillus and Clostridia-UCG-014, where the cecal tryptophan catabolite indole-3-acetic acid (IAA) and its ligand aryl hydrocarbon receptor (AhR) expressions were sharply increased by TPS treatment in colitis mice. Expectedly, TPS was found to exert its gut barrier functions through the activation of AhR to upregulate epithelial tight junction proteins. These findings highlight the protective effects of TPS against ulcerative colitis by modulating the gut microbiota and improving microbial metabolites and gut barrier function.