Regulating Gut Microbiota Research Articles

Oral Yak Whey Protein Can Alleviate UV-Induced Skin Photoaging and Modulate Gut Microbiota Composition.

Excessive UV exposure can lead to skin roughness, wrinkles, pigmentation, and reduced elasticity, with severe cases potentially causing skin cancer. Nowadays, various anti-photoaging strategies have been developed to maintain skin health. Among them, dietary supplements with anti-photoaging properties are gaining increasing attention. Yak whey protein (YWP) possesses multiple benefits, including anti-inflammatory, antioxidant, and immune-boosting properties, effectively protecting the skin. This study used a mixed UVA and UVB light source to irradiate a nude mouse model, exploring the advantages of YWP in anti-photoaging and regulating gut microbiota. The results indicated that YWP alleviated UV-induced skin damage, wrinkles, dryness, and reduced elasticity by inhibiting oxidative stress, inflammatory factors (IL-1α, IL-6, and TNF-α), and matrix metalloproteinases (MMP-1, MMP-3, and MMP-12), thereby increasing the levels of elastin, type I collagen, and type III collagen in the extracellular matrix (ECM). Additionally, YWP significantly improved the abundance of Firmicutes and Bacteroidota in the gut microbiota of mice, promoting the growth of beneficial bacteria such as Lachnospiraceae_NK4A136_group, Ruminococcus_torques_group, and Clostridia_UCG_014, mitigating the dysbiosis caused by photoaging. These findings underscore the potential of YWP in anti-photoaging and gut microbiota improvement, highlighting it as a promising functional food for enhancing skin and gut health.

Astragaloside IV Ameliorates Colonic Adenomatous Polyps Development by Orchestrating Gut Bifidobacterium and Serum Metabolome.

Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed [Formula: see text] mice. [Formula: see text] mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1β, IL-6, and TNF-α), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/β-catenin pathway proteins (Wnt3a, β-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed [Formula: see text] mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed [Formula: see text] mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/β-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects.

A preliminary examination of gut microbiota and emotion regulation in 2- to 6-year-old children

A preliminary examination of gut microbiota and emotion regulation in 2- to 6-year-old children

Polysaccharides from bile Arisaema exert an antipyretic effect on yeast-induced fever rats through regulating gut microbiota and metabolic profiling

In our previous study, bile Arisaema was elucidated to have a significant anti-febrile effect, but the pharmacodynamic material basis of this effect remains uncertain. Herein, we found that the soluble polysaccharide fraction from bile Arisaema presents a remarkable antipyretic effect through balancing the gut microbiota and regulating metabolic profiling. Bile Arisaema polysaccharide (BAP) was characterized for its monosaccharide composition with arabinose, galactose, glucose, mannose and xylose (0.028:0.072:0.821:0.05:0.029, molar ratios) and amino acid composition with arginine, threonine, alanine, glycine, serine, proline and tyrosine (109.33, 135.78, 7.22, 8.86, 21.07, 4.96, 12.31 μg/mg). A total of 50 peptides were identified from BAP using Ltq-Orbitrap MS/MS. The oral administration of 100 mg/kg BAP significantly increased the antipyretic effect in yeast-induced fever rats by comparing the rectal temperature. Mechanistically, the inflammation and disorders of neurotransmitters caused by fever were improved by treatment with BAP. The western blotting results suggested that BAP could suppress fever-induced inflammation by down-regulating the NF-κB/TLR4/MyD88 signaling pathway. We also demonstrated that BAP affects lipid metabolism, amino acid metabolism and carbohydrate metabolism and balances the gut microbiota. In summary, the present study provides a crucial foundation for determining polysaccharide activity in bile Arisaema and further investigating the underlying mechanism of action.

Huperzine a ameliorates sepsis-induced acute lung injury by suppressing inflammation and oxidative stress via α7 nicotinic acetylcholine receptor

Sepsis, characterized by high mortality rates, causes over 50 % of acute lung injury (ALI) cases, primarily due to the heightened susceptibility of the lungs during this condition. Suppression of the excessive inflammatory response is critical for improving the survival of patients with sepsis; nevertheless, no specific anti-sepsis drugs exist. Huperzine A (HupA) exhibits neuroprotective and anti-inflammatory properties; however, its underlying mechanisms and effects on sepsis-induced ALI have yet to be elucidated. In this study, we demonstrated the potential of HupA for treating sepsis and explored its mechanism of action. To investigate the in vivo impacts of HupA, a murine model of sepsis was induced through cecal ligation and puncture (CLP) in both wild-type (WT) and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. Our results showed that HupA ameliorates sepsis-induced acute lung injury by activating the α7nAChR. We used the CLP sepsis model in wild-type and α7nAChR −/− mice and found that HupA significantly increased the survival rate through α7nAChR, reduced the pro-inflammatory cytokine levels and oxidative stress, ameliorated histopathological lung injury, altered the circulating immune cell composition, regulated gut microbiota, and promoted short-chain fatty acid production through α7nAChR in vivo. Additionally, HupA inhibited Toll-like receptor NF-κB signaling by upregulating the α7nAChR/protein kinase B/glycogen synthase kinase-3 pathways. Our data elucidate HupA’s mechanism of action and support a “new use for an old drug” in treating sepsis. Our findings serve as a basis for further in vivo studies of this drug, followed by application to humans. Therefore, the findings have the potential to benefit patients with sepsis.

Shenling Baizhu powder attenuates lard diet in a fatigued state-induced diarrhea via targeting microbial metabolites short chain fatty acids-mediated lipid metabolism.

Shenling Baizhu Powder (SLBZP), a traditional Chinese medicine (TCM) prescription renowned for its efficacy, is specifically recognized for its therapeutic effects in managing diarrhea associated with spleen qi deficiency. Our previous research has demonstrated that a lard diet in a fatigued state induced diarrhea belonging to spleen qi deficiency in TCM. Through a comprehensive investigation, we aimed to provide insights into the intricate relationship between SLBZP and the modulation of gut microbiota in alleviating symptoms associated with spleen qi deficiency-induced diarrhea. We induced diarrhea in mice by subjecting them to continuous standing on a multiple-platform apparatus while administering lard through intragastric administration for 14days. Subsequently, we conducted gavage administration of SLBZP at a concentration of 0.637g/ml for seven days. We observed a therapeutic effect of SLBZP on diarrhea induced by a lard diet in a fatigued state. SLBZP mitigated disorders in lipid metabolism and diminished hepatic oxidative responses. Additionally, SLBZP reversed gut microbiota dysbiosis of diarrheic mice and notably increased the production of short-chain fatty acids (SCFAs), primarily acetic acid, butyric acid, and valeric acid. Through correlation analysis, we additionally identified Lactobacillus reuteri and Lactobacillus intestinalisas potentially pivotal species associated with the therapeutic effects of SLBZP. We demonstrated that SLBZP exerts therapeutic effects on diarrhea caused by a lard diet in a fatigued state by repairing the intestinal mucosal barrier, improving lipid metabolism disorders, and regulating gut microbiota and metabolites SCFAs.

Effects of kimchi consumption on body fat and intestinal microbiota in overweight participants: A randomized, double-blind, placebo-controlled, single-center clinical trial

Obesity is caused by an energy imbalance and leads to metabolic syndrome and diseases. The gut microbiota, influenced by diet, crucially impacts obesity. Kimchi, a traditional Korean fermented food rich in lactic acid bacteria, may alter gut microbiota composition. This randomized, double-blind, placebo-controlled trial enrolled 90 participants (BMI 23–30 kg/m2) to investigate the anti-obesity effects of kimchi. Participants consumed 3000 mg of spontaneously fermented kimchi powder (S-K) or starter-fermented kimchi powder with Leuconostoc mesenteroides KCKM0828 (LMS-K) daily for 12 weeks, while the placebo group consumed lactose. Both the S-K and LMS-K groups exhibited a significant reduction in body fat mass compared to the placebo group (S-K: p = 0.004, LMS-K: p = 0.003). Kimchi consumption also increased the proportion of Akkermansia muciniphila while decreasing that of Proteobacteria. Cumulatively, these findings suggest that daily kimchi consumption may alleviate obesity symptoms by regulating gut microbiota.

Harnessing nature's pharmacy: investigating natural compounds as novel therapeutics for ulcerative colitis.

Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease, and UC diagnosis rates continue to rise throughout the globe. The research and development of new drugs for the treatment of UC are urgent, and natural compounds are an important source. However, there is a lack of systematic summarization of natural compounds and their mechanisms for the treatment of UC. We reviewed the literature in the databases below from their inception until July 2023: Web of Science, PubMed, China National Knowledge Infrastructure, and Wanfang Data, to obtain information on the relationship between natural compounds and UC. The results showed that 279 natural compounds treat UC through four main mechanisms, including regulating gut microbiota and metabolites (Mechanism I), protecting the intestinal mucosal barrier (Mechanism II), regulating intestinal mucosal immune response (Mechanism III), as well as regulating other mechanisms (Mechanism Ⅳ) such as cellular autophagy modulation and ferroptosis inhibition. Of these, Mechanism III is regulated by all natural compounds. The 279 natural compounds, including 62 terpenoids, 57 alkaloids, 52 flavonoids, 26 phenols, 19 phenylpropanoids, 9 steroids, 9 saponins, 8 quinonoids, 6 vitamins, and 31 others, can effectively ameliorate UC. Of these, terpenoids, alkaloids, and flavonoids have the greatest potential for treating UC. It is noteworthy to highlight that a total of 54 natural compounds exhibit their therapeutic effects by modulating Mechanisms I, II, and III. This review serves as a comprehensive resource for the pharmaceutical industry, researchers, and clinicians seeking novel therapeutic approaches to combat UC. Harnessing the therapeutic potential of these natural compounds may significantly contribute to the improvement of the quality of life of patients with UC and promotion of disease-modifying therapies in the future.

Effects of Several Tea-like Plants on Liver Injury Induced by Alcohol via Their Antioxidation, Anti-Inflammation, and Regulation of Gut Microbiota.

Liver injury induced by alcohol is a serious global health problem. Several tea-like plants are widely used as beverages, which are drunk like tea. In this study, the hepatoprotective effects of eight tea-like plant extracts with the intake of 200 mg/kg.bw/day were investigated and compared using a C57BL/6J mouse model of acute alcohol exposure, including sweet tea, vine tea, Rabdosia serra kudo, broadleaf holly leaf, mulberry leaf, bamboo leaf, Camellia nitidissima, and Akebia trifoliata peels. The results showed that the eight tea-like plants had hepatoprotective effects to different degrees against acute alcohol exposure via enhancing the activities of alcoholic metabolism enzymes, ameliorating oxidative stress and inflammation in the liver, as well as regulating gut microbiota. In particular, sweet tea, bamboo leaf, mulberry leaf, and Camellia nitidissima increased the activities of alcohol dehydrogenase or aldehyde dehydrogenase. Among these tea-like plants, sweet tea and Camellia nitidissima had the greatest hepatoprotective effects, and their bioactive compounds were determined by high-performance liquid chromatography. Chlorogenic acid, rutin, and ellagic acid were identified in sweet tea, and epicatechin, rutin, and ellagic acid were identified in Camellia nitidissima, which could contribute to their hepatoprotective action. These tea-like plants could be drunk or developed into functional food against alcoholic liver injury, especially sweet tea and Camellia nitidissima. In the future, the effects of sweet tea and Camellia nitidissima on chronic alcoholic liver diseases should be further investigated.

Effects of regulating gut microbiota by electroacupuncture in the chronic unpredictable mild stress rat model

ObjectiveThis study aims to investigate the effect of electroacupuncture (EA) treatment on depression, and the potential molecular mechanism of EA in depression-like behaviors rats. MethodsA total of 40 male Sprague Dawley rats were divided into three groups: normal control, chronic unpredictable mild stress (CUMS), and EA (CUMS + EA). The rats in CUMS and EA groups underwent chronic stress for 10 weeks, and EA group rats received EA treatment for 4 weeks starting from week 7. Body weight and behavioral tests, including the sucrose preference test (SPT), the forced swimming test (FST), and the open field test (OFT) were monitored. Gut microbiota composition was assessed via 16S rDNA sequencing, and lipid metabolism was analyzed by using UPLC-Q-TOF/MS technology. ResultsIn comparison to CUMS group, EA could improve the behavior including bodyweight, immovability time, sucrose preference index, crossing piece index and rearing times index. After 4 weeks of EA treatment, 5-HT in hippocampus, serum and colon of depressive rats were simultaneously increased, indicating a potential alleviation of depression-like behaviors. In future studies revealed that EA could regulate the distribution and functions of gut microbiota, and improve the intestinal barrier function of CUMS rats. The regulation of intestinal microbial homeostasis by EA may further affect lipid metabolism in CUMS rats, and thus play an antidepressant role. ConclusionThis study suggested that EA has potential antidepressant effects by regulating gut microbiota composition and abundance, subsequently affecting lipid metabolism.

Xiaoyankangjun tablet alleviates dextran sulfate sodium-induced colitis in mice by regulating gut microbiota and JAK2/STAT3 pathway

Xiaoyankangjun tablet (XYKJP) is a traditional Chinese medicine formulation used to treat intestinal disorders in clinical practice. However, the specific therapeutic mechanism of action of XYKJP in colitis has not yet been elucidated. This study aimed to reveal the multifaceted mechanisms of action of XYKJP in treating colitis. The model established based on DSS-induced colitis in C57BL/6 mice was employed to estimate the effect of XYKJP on colitis, which was then followed by histological assessment, 16S rRNA sequencing, RT-qPCR, ELISA, and Western blot. XYKJP alleviated the symptoms of DSS-induced colitis mainly by reducing oxidative stress, inflammatory responses, and intestinal mucosal repair in colitis tissues. In addition, XYKJP regulated the intestinal flora by increasing the relative abundance of Akkermansia and Bifidobacterium and reducing the relative abundance of Coriobacteriaceae_UCG-002. Mechanistically, XYKJP increased the content of short-chain fatty acids (SCFAs) in the feces, particularly propanoic acid and butyric acid, activated their specific receptor GPR43/41, furthermore activated the Nrf2/HO-1 pathway, and suppressed the JAK2/STAT3 pathway. XYKJP significantly alleviated the symptoms of experimental colitis and functioned synergistically by regulating the intestinal flora, increasing the production of SCFAs, and activating their specific receptors, thereby repressing oxidative stress and inflammation.Graphical

Resveratrol attenuates non-steroidal anti-inflammatory drug-induced intestinal injury in rats in a high-altitude hypoxic environment by modulating the TLR4/NFκB/IκB pathway and gut microbiota composition.

Non-steroidal anti-inflammatory drugs (NSAIDs) are currently the most widely used anti-inflammatory medications, but their long-term use can cause damage to the gastrointestinal tract(GIT). One of the risk factors for GIT injury is exposure to a high-altitude hypoxic environment, which can lead to damage to the intestinal mucosal barrier. Taking NSAIDs in a high-altitude hypoxic environment can exacerbate GIT injury and impact gut microbiota. The aim of this study is to investigate the mechanisms by which resveratrol (RSV) intervention alleviates NSAID-induced intestinal injury in a high-altitude hypoxic environment, as well as its role in regulating gut microbiota. Aspirin was administered orally to rats to construct a rat model of intestinal injury induced by NSAIDs. Following the induction of intestinal injury, rats were administered RSV by gavage, and the expression levels of TLR4, NF-κB,IκB as well as Zonula Occludens-1 (ZO-1) and Occludin proteins in the different treatment groups were assessed via Western blot. Furthermore, the expression of the inflammatory factors IL-10, IL-1β, and TNF-α was evaluated using Elisa.16sRNA sequencing was employed to investigate alterations in the gut microbiota. The HCk group showed elevated expression of TLR4/NF-κB/IκB pathway proteins, increased expression of pro-inflammatory factors IL-1β and TNF-α, decreased expression of the anti-inflammatory factor IL-10, and expression of intestinal mucosal barrier proteins ZO-1 and Occludin. The administration of NSAIDs drugs in the plateau hypoxic environment exacerbates intestinal inflammation and damage to the intestinal mucosal barrier. After treatment with RSV intervention, the expression of TLR4/NF-κB/IκB signaling pathway proteins would be reduced, thereby lowering the expression of inflammatory factors in the HAsp group. The results of HE staining directly show the damage to the intestines and the repair of intestinal mucosa after RSV intervention. 16sRNA sequencing results show significant differences (P<0.05) in Ruminococcus, Facklamia, Parasutterella, Jeotgalicoccus, Coprococcus, and Psychrobacter between the HCk group and the Ck group. Compared to the HCk group, the HAsp group shows significant differences (P<0.05) in Facklamia, Jeotgalicoccus, Roseburia, Psychrobacter, and Alloprevotella. After RSV intervention, Clostridium_sensu_stricto bacteria significantly increase compared to the HAsp group. Resveratrol can attenuate intestinal damage caused by the administration of NSAIDs at high altitude in hypoxic environments by modulating the TLR4/NF-κB/IκB signaling pathway and gut microbiota composition.

Oxymatrine alleviates NSAID-associated small bowel mucosal injury by regulating MIP-1/CCR1 signalling and gut microbiota

Oxymatrine (OMT) as a quinazine alkaloid extracted from matrine has been shown to exhibit anti-inflammatory and anti-tumour effects. However, the protective mechanism of OMT on NSAID-associated small bowel mucosal injury remains unreported. We found that OMT could improve the clinical symptoms and pathological inflammation scoring, reduce the secretion of proinflammatory cytokines IL-1β, IL-6 and TNF-α and cell apoptosis, promote cell proliferation and protect intestinal mucosal barrier as compared with the Diclofenac Sodium (DS) group. Further RNA-seq and KEGG analysis uncovered that the differentially expressed genes between DS and control groups were mainly enriched in immune regulation, of which MIP-1γ and its receptor CCR1 expression were validated to be repressed by OMTH. MAPK/NF-κB as the MIP-1 upstream signalling was also inactivated by OMT treatment. In this study, OMT regulated gut microbiota. Venn diagrams visualized and identified 1163 shared OTUs between DS group and OMTH group. The results showed that the α diversity index in the DS group was lower than that in the OMTH group, indicating that the complexity of the flora was reduced in the intestinal inflammatory state. β diversity mainly includes Principal Component Analysis (PCA) and Principal Co-ordinates Analysis (PCoA). The differences between groups can be observed through PCA. The more similar the composition of the flora, the closer the samples are. We found that the difference was smaller in the DS group than in the OMTH group. The results of PcoA showed that the sample similarity between OMTH groups was the highest. Moreover, gut microbiota analysis unveiled that the abundances of Ruminococcus 1, Oscillibacter and Prevotellaceae at the genus level as well as Lactobacillus SP-L-Yj at the species level were increased in OMTH group as compared with the DS group but the abundance of Allobaculum, Ruminococceos-UCG-005, Ruminococceos-NK4A214 and Clostridium associated with DS-induced small bowel mucosal injury could be decreased by OMTH. MIP-1α and CCR1 were upregulated in human small bowel injury samples as compared with the normal ileal mucosa tissues. In conclusion, our findings demonstrated that OMT could alleviate NSAID-associated small bowel mucosal injury by inhibiting MIP-1γ/CCR1 signalling and regulating gut microbiota.

Exploring the correlation between gut microbiota and benign gastric tumors: A Mendelian randomization study.

Recent scientific research has verified a link between malignant tumors in the stomach and the gut microbiota. This research employed Mendelian randomization (MR) techniques to explore the association between gut microbiota and benign gastric malignancies. The data were derived from genome wide association studies-aggregated data consisting of 211 gut microbes and benign gastric lesions and analyzed by MR. Five statistical tools, including inverse variance weighting, weighted median, MR-Egger, simple mode, and weighted mode, were employed in the statistical analysis. The utilization of the leave-one-out approach served as an effective means of detecting data outliers. Furthermore, implementing Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and MR-Egger intercepts was employed to mitigate the impact of horizontal pleiotropy. The Cochran Q scores for inverse variance weighting and MR-Egger were utilized to determine the extent of heterogeneity. The findings indicate that the family Porphyromonadaceae (odds ratio [OR] = 2.185, 95% confidence interval [CI]: 1.239-3.855, P = .007), class Bacilli (OR = 1.556, 95%CI: 1.091 - 2.220, P = .015), family Lactobacillaceae (OR = 1.437, 95%CI: 1.049 - 1.969, P = .024), family Oxalobacteraceae (OR = 1.290, 95%CI: 1.035 - 1.608, P = .023) are positively associated with the occurrence of benign gastric tumors. Conversely, the family Pasteurellaceae (OR = 0.752, 95%CI: 0.566 - 0.999, P = .049) and family Peptococcaceae (OR = 0.622, 95%CI: 0.425 - 0.908, P = .014) exhibit a protective effect and significantly decrease the likelihood of benign gastric tumors. The findings of this study suggest that the probability of developing benign gastric tumors is positively associated with the presence of the family Porphyromonadaceae, class Bacilli, family Lactobacillaceae and family Oxalobacteraceae, In contrast, the presence of the family Pasteurellaceae and family Peptococcaceae is negatively associated with this risk. Therefore, regulating gut microbiota may be a potential strategy to reduce the incidence of benign gastric tumors.

Silymarin targets the FXR protein through microbial metabolite 7-keto-deoxycholic acid to treat MASLD in obese mice

BackgroundSilymarin is recognized for its excellent hepato-protective properties. Recent clinical studies have examined the effects of silymarin on metabolic dysfunction-associated steatotic liver disease (MASLD), highlighting the necessity of further exploration into optimal dosages, active components, and mechanisms of action. Methods and resultsThis study assessed the anti-inflammatory activity of the principal constituents of silymarin at the cellular level. The therapeutic effects of varying silymarin doses and components on MASLD in mouse models induced by a high-fat diet (HFD) were also examined. These findings indicate the superior efficacy of 80 mg kg-1 silymarin in mitigating liver steatosis and reducing lipid accumulation compared to 30 mg kg-1 silymarin or a combination of silybin and isosilybin A. The mechanism of silymarin involves regulating gut microbiota homeostasis and influencing the TLR4/NF-κB signalling pathway through LPS. Bile acid-targeted metabolomics analysis revealed that silymarin significantly decreases the HFD-induced increase in 7-keto-deoxycholic acid (7-KDCA). Further investigations suggested that 7-KDCA as an antagonist targeted farnesoid X receptor (FXR) and that both silybin and isosilybin A could directly interact with FXR. ConclusionThese findings elucidate that 80 mg kg-1 of silymarin can exert therapeutic effects on MASLD mice and offer novel insights into the mechanism of silymarin in treating MASLD. Especially, it was found that silymarin could regulate bile acid metabolism, reduce the concentration of 7-KDCA, and thus perform negative feedback regulation on FXR.

TFEB activator tanshinone IIA and derivatives derived from Salvia miltiorrhiza Bge. Attenuate hepatic steatosis and insulin resistance

Ethnopharmacological relevanceSalvia miltiorrhiza Bge. (SMB) is an herbal medicine extensively used for improving metabolic disorders, including Nonalcoholic fatty liver disease (NAFLD). However, the potential material basis and working mechanism still remained to be elucidated. Aim of the studyTo find potential ingredients for therapy of NAFLD by high content screening and further verify the efficacy on restoring hepatic steatosis and insulin resistance, and clarify the potential working mechanism. Materials and methodsThe mouse transcription factor EB (Tfeb) in preadipocytes was knocked out by CRISPR-Cas9 gene editing. High content screening of TFEB nuclear translocation was performed to identify TFEB activators. The effect of candidate compounds on reducing lipid accumulation was evaluated using Caenorhabditis elegans (C. elegans). Then the role of Salvia miltiorrhiza extract (SMB) containing Tanshinone IIA and the derivatives were further investigated on high-fat diet (HFD) fed mice. RNA-seq was performed to explore potential molecular mechanism of SMB. Finally, the gut microbiota diversity was evaluated using 16S rRNA sequencing to investigate the protective role of SMB on regulating gut microbiota homeostasis. ResultsKnockout of Tfeb led to excessive lipid accumulation in adipocytes while expression of TFEB homolog HLH-30 in C. elegans (MAH240) attenuated lipid deposition. Screening of TFEB activators identified multiple candidates from Salvia miltiorrhiza, all of them markedly induced lysosome biogenesis in HepG2 cells. One of the candidate compounds Tanshinone IIA significantly decreased lipid droplet deposition in HFD fed C. elegans. Administration of SMB on C57BL/6J mice via gastric irrigation at the dose of 15 g/kg/d markedly alleviated hepatic steatosis, restored serum lipid profile, and glucose tolerance. RNA-seq showed that gene expression profile was altered and the genes related to lipid metabolism were restored. The disordered microbiome was remodeled by SMB, Firmicutes and Actinobacteriotawere notably reduced, Bacteroidota and Verrucomicrobiota were significantly increased. ConclusionTaken together, the observations presented here help address the question concerning what were the main active ingredients in SMB for alleviating NAFLD, and established that targeting TFEB was key molecular basis for the efficacy of SMB.

Study on the physicochemical properties and gut microbiota regulation of Poria cocos pachyman treated by ball milling

The effect of ball milling on the physicochemical properties and gut microbiota regulation of Poria cocos pachyman (PAC) was investigated. Ball milling reduced the particle size of PAC from 102 μm to 25.19 μm after 12 h, resulting in increasing particle uniformity. Scanning electron microscopy (SEM) revealed surface roughening and fragmentation of PAC after ball milling. X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) indicated reduced crystallinity and increased hydroxyl group exposure in ball-milled PAC (BMP). Thermogravimetric analysis (TGA) showed decreased thermal stability in BMP. The optimal ball milled time was 7 h. Moisture contents in PAC and BMP-7 h were 10.30 ± 0.47 % and 10.72 ± 0.12 %, and carbohydrate contents were 81.02 ± 2.27 % and 74.54 ± 1.46 %. In vivo studies on mice demonstrated that both PAC and BMP-7 h increased diversity and reshaped the composition of gut microbiota, with BMP-7 h showing a more pronounced effect. BMP-7 h reduced the Firmicutes/Bacteroidetes ratio, and raised the abundance of Bacteroides, suggesting enhanced prebiotic potential. These findings highlight the role of ball milling in improving the physicochemical properties and prebiotic potential of water-insoluble polysaccharides and provide a theoretical basis for its broader application in the food and biopharmaceutical industries.

Chemical Profile and In Vitro Gut Microbiota Modulation of Wild Edible Mushroom Phallus atrovolvatus Fruiting Body at Different Maturity Stages.

Phallus atrovolvatus, a wild edible mushroom, has attracted increasing interest for consumption due to its unique taste and beneficial health benefits. This study determined the chemical components in the so-called fruiting body during the egg and mature stages and investigated its gut microbiota-modulating activities. The egg stage contained higher total carbohydrates, dietary fiber, glucans, ash, and fat, while the total protein content was lower than in the mature stage. Two consumption forms, including cooked mushrooms and a mushroom aqueous extract from both stages, were used in this study. An in vitro gut fermentation was performed for 24 h to assess gut microbiota regulation. All mushroom-supplemented fermentations increased short-chain fatty acid (SCFA) production compared to the blank control. Furthermore, all mushroom supplementations promoted the growth of Bifidobacterium and Streptococcus. Samples from the mature stage increased the relative abundance of Clostridium sensu stricto 1, while those from the egg stage increased the Bacteroides group. The inhibition of harmful bacteria, including Escherichia-Shigella, Klebsiella, and Veillonella, was only observed for the mature body. Our findings demonstrate that P. atrovolvatus exhibits potential benefits on gut health by promoting SCFA production and the growth of beneficial bacteria, with the mature stage demonstrating superior effects compared to the egg stage.

Attenuation of arsenic-induced gut injury in mice by sulfated glycosaminoglycan from swim bladder via regulation of gut microbiota, metabolites, and intestinal barrier integrity

Attenuation of arsenic-induced gut injury in mice by sulfated glycosaminoglycan from swim bladder via regulation of gut microbiota, metabolites, and intestinal barrier integrity

Mechanism of Action of Qingrekasen Granules in Alleviating Nephrotic Syndrome Evaluated by a Multi-Omics Approach

Objectives In this study, the efficacy of and mechanism of Qingrekasen Granules (QRKSG) is evaluated by metabolomics and transcriptomics using adriamycin (ADR)-induced nephrotic syndrome (NS) in rat model. Methods The model, benazepril, and QRKSG group received a single injection of 6.5 mg/kg ADR via the tail vein of the rats. The untreated group received an equal saline injection. The administration of drugs by gavage began after completing the modeling for one week. Benazepril was given at 0.9 mg/kg/d to the benazepril group and QRKSG was given at 1.62 g/kg/d to the QRKSG group. During gavage, 24 h urine was collected weekly. After four weeks of gavage, rats were anesthetized, and we collected the serum, feces, and kidney samples. The protective effect of QRKSG on NS was assessed by the detection of proteins in the urine at 24 h and serum biochemical indexes, as well as histopathological observation, TUNEL assay, and Western Blot of kidney samples. Moreover, gas chromatography-mass spectrometry (GC-MS) metabolomics sequencing of kidney metabolites helped investigate the significant differential metabolites produced by QRKSG that are implicated in ameliorating the pathological damage to the kidneys of NS rats. Subsequently, the significant targets of QRKSG that had an impact on the action of drugs were investigated by a transcriptome sequencing analysis. The correlation between both sets was also investigated. In addition, the effect of QRKSG on the gut microbiota of NS rats was investigated. Finally, the core targets were validated by molecular docking. Results The results indicated that QRKSG possess significant renoprotective effects in NS rats by reversing the abnormal urinary protein content and serum biochemical disorders, as well as improving renal pathological damage. Multiple genes and metabolites were shown to be back-regulated after QRKSG delivery, based on further multi-omics studies. The integrated metabolomics and transcriptomics analysis showed that QRKSG alleviated NS mainly by regulating amino acid metabolic pathways. Gut microbiota analysis demonstrated that QRKSG could alleviate NS by improving gut microbiota. The molecular docking results showed good binding ability of the QRKSG active ingredient to the core target, and among them, the ingredients with the best docking effect were mainly flavonoids and phenolic acid ingredients. The combined metabolomics and transcriptomics study findings were validated through a TUNEL assay and a Western Blot analysis. Conclusion We have concluded that ADR-induced NS in rats can be treated with QRKSG. The mechanisms used by QRKSG to reduce the symptoms of NS are through the multi-component, multi-target, and multi-pathway therapeutic modulation of inflammation, oxidative stress, energy homeostasis, and apoptosis. Additionally, QRKSG could alleviate NS by regulating gut microbiota.