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.

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.

Quantification of myocardial hemorrhage using T2* cardiovascular magnetic resonance at 1.5T with ex-vivo validation.

BACKGROUND: T2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* < 20 ms)] are interchangeably used. We examined whether these approaches yield equivalent information. METHODS: ST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4-7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* < 20 ms. In animals, ex-vivo T2* CMR and mass spectrometry for iron concentration ([Fe]Hemo) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe]Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*. RESULTS: While both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* < 20 ms showed lower T2* and volume of IMH in patients and animals independent of MI age (all p < 0.005). While T2* determined from both methods were highly correlated against [Fe]Hemo (R2 = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* < 20 ms (0.46 vs. 0.32, p < 0.01). Further, slightly larger absolute T2* cut-offs (patients: 23 ms; animals: 25 ms) showed similar IMH characteristics compared to ssT2*. CONCLUSION: Current quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2* < 20 ms are smaller compared to ssT2*. Thus the method used to quantify IMH from T2* CMR may influence the diagnosis for IMH.

Assessment of intramyocardial hemorrhage with dark-blood T2*-weighted cardiovascular magnetic resonance.

BACKGROUND: Intramyocardial hemorrhage (IMH) within myocardial infarction (MI) is associated with major adverse cardiovascular events. Bright-blood T2*-based cardiovascular magnetic resonance (CMR) has emerged as the reference standard for non-invasive IMH detection. Despite this, the dark-blood T2*-based CMR is becoming interchangeably used with bright-blood T2*-weighted CMR in both clinical and preclinical settings for IMH detection. To date however, the relative merits of dark-blood T2*-weighted with respect to bright-blood T2*-weighted CMR for IMH characterization has not been studied. We investigated the diagnostic capacity of dark-blood T2*-weighted CMR against bright-blood T2*-weighted CMR for IMH characterization in clinical and preclinical settings. MATERIALS AND METHODS: Hemorrhagic MI patients (n = 20) and canines (n = 11) were imaged in the acute and chronic phases at 1.5 and 3 T with dark- and bright-blood T2*-weighted CMR. Imaging characteristics (Relative signal-to-noise (SNR), Relative contrast-to-noise (CNR), IMH Extent) and diagnostic performance (sensitivity, specificity, accuracy, area-under-the-curve, and inter-observer variability) of dark-blood T2*-weighted CMR for IMH characterization were assessed relative to bright-blood T2*-weighted CMR. RESULTS: At both clinical and preclinical settings, compared to bright-blood T2*-weighted CMR, dark-blood T2*-weighted images had significantly lower SNR, CNR and reduced IMH extent (all p < 0.05). Dark-blood T2*-weighted CMR also demonstrated weaker sensitivity, specificity, accuracy, and inter-observer variability compared to bright-blood T2*-weighted CMR (all p < 0.05). These observations were consistent across infarct age and imaging field strengths. CONCLUSION: While IMH can be visible on dark-blood T2*-weighted CMR, the overall conspicuity of IMH is significantly reduced compared to that observed in bright-blood T2*-weighted images, across infarct age in clinical and preclinical settings at 1.5 and 3 T. Hence, bright-blood T2*-weighted CMR would be preferable for clinical use since dark-blood T2*-weighted CMR carries the potential to misclassify hemorrhagic MIs as non-hemorrhagic MIs.

M2 macrophage-derived exosomes carry microRNA-148a to alleviate myocardial ischemia/reperfusion injury via inhibiting TXNIP and the TLR4/NF-κB/NLRP3 inflammasome signaling pathway.

BACKGROUND: Reperfusion may cause injuries to the myocardium in ischemia situation. Emerging studies suggest that exosomes may serve as key mediators in myocardial ischemia/reperfusion (MI/R) injury. OBJECTIVE: The study was conducted to figure out the mechanism of M2 macrophage-derived exosomes (M2-exos) in MI/R injury with the involvement of microRNA-148a (miR-148a). METHODS AND RESULTS: M2 macrophages were prepared and M2-exos were collected and identified. Neonatal rat cardiomyocytes (NCMs) were extracted for in vitro hypoxia/reoxygenation (H/R) model establishment, while rat cardiac tissues were separated for in vivo MI/R model establishment. Differentially expressed miRNAs in NCMs and H/R-treated NCMs after M2-exos treatment were evaluated using microarray analysis. The target relation between miR-148a and thioredoxin-interacting protein (TXNIP) was identified using dual luciferase reporter gene assay. Gain- and loss- of function studies of miR-148a and TXNIP were performed to figure out their roles in MI/R injury. Meanwhile, the activation of the TLR4/NF-κB/NLRP3 inflammasome signaling pathway and pyroptosis of NCMs were evaluated. M2 macrophages carried miR-148a into NCMs. Over-expression of miR-148a enhanced viability of H/R-treated NCMs, reduced infarct size in vivo, and alleviated dysregulation of cardiac enzymes and Ca2+ overload in both models. miR-148a directly bound to the 3'-untranslated region (3'UTR) of TXNIP. Over-expressed TXNIP triggered the TLR4/NF-κB/NLRP3 signaling pathway activation and induced cell pyroptosis of NCMs, and the results were reproduced in in vivo studies. CONCLUSION: This study demonstrated that M2-exos could carry miR-148a to mitigate MI/R injury via down-regulating TXNIP and inactivating the TLR4/NF-κB/NLRP3 inflammasome signaling pathway. This study may offer new insights into MI/R injury treatment.

Protective Effect of Saponins-Enriched Fraction of Gynostemma pentaphyllum against High Choline-Induced Vascular Endothelial Dysfunction and Hepatic Damage in Mice.

Choline as a quaternary amine nutrient is metabolized to trimethylamine by gut microbiota and subsequently oxidized to circulating trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with liver toxicity and cardiovascular disease. The study was to probe the possible vasoprotective and hepatoprotective effects of total saponins of Gynostemma pentaphyllum (TSGP) in 3% high-choline water-feeding mice. The purified TSGP was obtained with content of 83.0% saponins, and its antioxidant activities were evaluated in vitro. Furthermore, the mice fed with high choline for 8 weeks significantly expressed vascular endothelial dysfunction and liver oxidative stress (p < 0.01 vs. Normal). Administration of TSGP at 400 and 800 mg/kg·body weight (b.w.) significantly lowered the serum total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), endothelin-1 (ET-1) and thromboxane A2 (TXA2) levels, as well as hepatic malondialdehyde (MDA) formation, but effectively elevated the serum nitric oxide (NO), endothelial nitric oxide synthase (eNOS) and prostaglandin I2 (PGI2) levels, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), T-superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in high choline-fed mice. Hematoxylin-eosin (H&E) and oil red O staining also suggested that TSGP could exert the significant protection against endothelial dysfunction and liver injury in high choline-treated mice. These findings suggest that TSGP is of the saponins-enriched extract, and is a good candidate of dietary supplement and therapeutic application in vascular and hepatic oxidative injury.

Myocardial extracellular volume fraction measurement in chronic total coronary occlusion: Association with myocardial injury, angiographic collateral flow, and functional recovery.

PURPOSE: To investigate whether myocardial extracellular volume fraction (ECV) measurement by cardiac MR is indicative of myocardial injury, angiographic collateral flow, and functional recovery in patients with chronic total coronary occlusion (CTO). MATERIALS AND METHODS: A total of 50 CTO patients undergoing 1.5 Tesla MR were prospectively enrolled, and 28 underwent a second MR 6 months after revascularization. T1-mapping based indices, including pre- and postcontrast T1 values and ECV, were obtained from infarcted and non-infarcted myocardium, myocardial segments, and coronary territory. The severity of myocardial injury was rated by transmurality extent of infarction (TEI) and regional wall motion abnormalities (RWMA) score. Angiographic collateral flow was evaluated using Rentrop classification. Improvement in segmental wall motion at 6 months was also assessed. RESULTS: ECV and postcontrast T1 value significantly outperformed precontrast T1 value for identifying myocardial infarction (area under the receiver operating characteristic curve [AUC]: 0.998 and 0.953 versus 0.824, all P < 0.02). Myocardial ECV was strongly correlated with TEI (P = 0.000), RWMA score (P = 0.000), and collateral classification (P = 0.007 for left anterior descending artery [LAD] territory, P = 0.001 for non-LAD territory). Furthermore, the likelihood of functional recovery was better predicted by ECV than by late gadolinium enhancement (LGE) (AUC: 0.76 versus 0.68, P < 0.02). CONCLUSION: Myocardial ECV may be a useful surrogate to assess myocardial injury and angiographic collateral flow in CTO, and ECV provides incremental value to LGE in assessing functional recovery after revascularization. J. MAGN. RESON. IMAGING 2016;44:972-982.

[Gene function of glpX in mycobacterium].

OBJECTIVE: To investigate the function of glpX gene in mycobacterial physiology and metabolism. METHODS: The glpX mutant of Mycobacterium smegmatis was constructed byusing mycobacteriophage Che9c-encoded recombination system. Then the growth difference between mutant and wild type strain was compared on various carbon sources. Furthermore, we analyzed the glpX gene transcriptional level of wild type strain growing on glucose or oleic acid by realtime PCR. RESULTS: The growth of M. smegmatis on glycerol or oleic acid is strongly attenuated after the deletion of the glpX gene. The transcription of glpX gene is upregulated in the medium with oleic acid as the sole carbon source. CONCLUSION: These results indicate that the fructose 1,6-bisphosphatase encoded by glpX gene is required and nonredundant for mycobacterial gluconeogenesis.

[MicroRNA-210 mediates the protective effect of rosuvastatin on human mesenchymal stem cells apoptosis induced by tumor necrosis factor-α].

OBJECTIVE: To explore the effect and mechanism of rosuvastatin on tumor necrosis factor-α induced human mesenchymal stem cells (MSCs) apoptosis. METHOD: Human MSCs were treated as follows: (1) culture medium; (2) TNF-α (20 µg/ml) for 6 h; (3) rosuvastatin (20 µmol/L) for 24 h; (4) rosuvastatin (20 µmol/L) for 24 h followed by TNF-α (20 µg/ml) for 6 h; (5) TNF-α+rosuvastatin+50 nmol/L antago-miRNA; (6) TNF-α+rosuvastatin+100 nmol/L antago-miRNA. Cell survival and apoptosis were determined by MTT, TUNEL and caspase-3 activity assay. The changes of miRNA-210 in each group were detected with quantitative PCR. RESULT: TNF-α significantly induced human MSCs apoptosis in a concentration-dependent manner, and pretreatment with rosuvastatin significantly reduced MSCs apoptosis (caspase-3 assay: TNF-α+Statin group vs. TNF-α group: (1.63 ± 0.25) vs. (2.05 ± 0.36), P < 0.05). Meanwhile, TNF-α progressively reduced the expression of miRNA-210 in human MSCs in a dose-dependent manner, while the miRNA-210 expression was significantly upregulated in TNF-α+Statin group (P < 0.05). The protective effect of rosuvastatin on TNF-α induced MSCs apoptosis was largely abolished by co-treatment with 100 nmol/L antago-miRNA (TUNEL:TNF-α + Statin + antago-miR group vs. TNF-α + Statin group: (42.58 ± 6.71) % vs. (16.87 ± 9.27) %, P < 0.05). CONCLUSION: Pretreatment with rosuvastatin can significantly improve the viability of human MSCs after TNF-α injury, the protective mechanism of rosuvastatin is partly mediated through miRNA-210 up-regulation.

Intracellular Polysaccharides of Eurotium cristatum Exhibited Anticolitis Effects in Association with Gut Tryptophan Metabolism.

This study is to investigate the protective effects of Eurotium cristatum intracellular polysaccharides (ECIP) on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC). The oral administration of ECIP could downregulate the disease activity index (DAI) and ameliorate the colonic shortening, immune stress, and damage caused by DSS. In addition, ECIP treatment increased the colonic contents of SCFAs including acetic, propionic, and butyric acids in UC mice. Targeted and untargeted metabolic analysis suggested that ECIP dramatically altered the tryptophan metabolism in the feces of UC mice and promoted the conversion of tryptophan into indole metabolites including indolepyruvate and indole-3-acetic acid (IAA) and indolealdehyde (IAId). Moreover, ECIP observably increased the content of colonic IL-22 and stimulated the relative concentration and relative expression of tight junction molecules in mRNA and proteins levels. Conclusively, consumption of ECIP can improve colon damage and its related effects of UC by promoting the production of IAA and IAId to reinforce intestinal barriers.

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.

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.

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.

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.

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.

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.

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.

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.