Ovarian Microcystic Stromal Tumor with Significant Nestin Expression: A Unique Case.

Ovary microcystic stromal tumor (MCST) is an extremely rare subtype of sex cord-stromal neoplasm, and only 57 cases have been reported. We herein report a unique case of ovarian MCST with positive nestin expression in a 39-year-old Chinese woman. The tumor showed microcystic stromal histological structures and characteristically expressed the CD10, WT-1, and Ki67 proteins. A molecular analysis identified a point mutation (c.110C > T) in exon 3 of the CTNNB1 gene. To our knowledge, no report has described a case of ovarian MCST with positive staining for nestin protein. Our study provides new insights into the tumor biology of ovarian MCST.

Gut microbiota-based discovery of Houttuyniae Herba as a novel prebiotic of Bacteroides thetaiotaomicron with anti-colitis activity.

Ulcerative colitis (UC) represents an inflammatory disease characterized by fluctuations in severity, posing substantial challenges in treatment. The gut microbiota plays a pivotal role in the pathogenesis of UC. This study sought to identify drugs specifically targeting the gut microbiota to mitigate UC. We initiated a meta-analysis on gut microbiota in UC patients to identify UC-associated bacterial strains. Subsequently, we screened 164 dietary herbal medicines in vitro to identify potential prebiotics for the UC-associated bacterium, Bacteroides thetaiotaomicron. The DSS-induced colitis mouse model was utilized to evaluate the anti-colitis efficacy of the identified dietary herbal medicine. Full-length 16 S rRNA amplicon sequencing was employed to observe changes in gut microbiota following dietary herbal medicine intervention. The relative abundance of Bacteroides was notably diminished in UC patients compared to their healthy counterparts. B. thetaiotaomicron exhibited an inverse relationship with UC symptoms, indicating its potential as an anti-colitis agent. In vitro assessments revealed that H. Herba significantly bolstered the proliferation of B. thetaiotaomicron. Further experiments showed that treating DSS-induced mice with an aqueous extract of H. Herba considerably alleviated colitis indicators such as weight loss, colon shortening, disease activity score (DAI), and systemic inflammation. Microbial analysis revealed B. thetaiotaomicron as the sole bacterium substantially augmented by H. Herba in vivo. Overall H. Herba emerges as a promising prebiotic for B. thetaiotaomicron, offering significant anti-colitis benefits. Employing a gut microbiota-centric approach proves valuable in the quest for drug discovery.This study provides a new paradigm for drug discovery that targets the gut microbiota to treat UC.

Potential efficacy and mechanism of eight mild-natured and bitter-flavored TCMs based on gut microbiota: A review.

The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

Modulative effect of Physalis alkekengi on both gut bacterial and fungal micro-ecosystem.

Objective: Gut microbiome is an intricate micro-ecosystem mediating the human health and drug efficacy. Physalis alkekengi (PAL) is an edible and time-honored traditional Chinese medicine. Several pharmacological effects of PAL have been verified and gut bacteria are implied in its therapeutic actions. However, the detailed modulation of PAL on gut bacterial species and on gut fungi remains largely unknown. We, therefore, designed a preliminary experiment in normal mice to reveal the modulation effect of PAL on both gut bacteria and fungi, and explore the interaction between them. Methods: Herein, the aqueous extract of PAL was orally administrated to normal C57BL/6 mice for four weeks. The full-length 16S rRNA and ITS1/2 gene sequencing were explored to detect the taxa of gut bacteria and gut fungi after PAL treatment, respectively. Results: Oral administration of PAL notably enriched anti-inflammatory bacterial species such as Duncaniella spp. and Kineothrix alysoides, whereas decreased pro-inflammatory species such as Mucispirillum schaedleri. Simultaneously, PAL increased the abundance of gut fungi Aspergillus ochraceus, Cladosporium sp. and Alternaria sp., and decreased Penicillium janthinellum. Correlation network analysis identified two co-existing microbial groups (groups 1 and 2) that were negatively associated with each other. The group 1 comprised PAL-enriched bacteria and fungi, while group 2 was mainly normal chow-enriched bacteria and fungi. In group 1, Antrodia monomitica, Aspergillus clavatus, Mortierella kuhlmanii and Sarcinomyces sp. MA 4787 were positively correlated with Bifidobacterium globosum, Romboutsia ilealis and so on. In group 2, Chaetomium subspirilliferum, Septoria orchidearum and Cephaliophora tropica were positively related to Lactobacillus spp. Conclusion: Altogether, this preliminary study first demonstrated the modulation effect of PAL on both gut bacteria and gut fungi, which may shed light on the elucidation of PAL's pharmacological mechanism.

Oral Intake of Inosine 5'-Monophosphate in Mice Promotes the Absorption of Exogenous Fatty Acids and Their Conversion into Triglycerides though Enhancing the Phosphorylation of Adenosine 5'-Monophosphate-Activated Protein Kinase in the Liver, Leading to Lipohyperplasia.

Inosine 5'-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57/KsJ-db/db (db/db) mice. Thus, IMP taken orally by healthy mice might also damage their health. To date, how IMP affects health after being taken by healthy animals is still unclear. Therefore, we investigated the health of C57BL/6J mice affected by IMP intake. Our data revealed that C57BL/6J mice administered 255 µM IMP daily via oral gavage for 4 months caused hyperlipidemia and an increase in body fat rate. The expressions of acetyl-CoA carboxylase 1 (ACC1) and phosphorylated acetyl-CoA carboxylase 2 (ACC2) in hepatocytes increased though the administration of IMP, promoting the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK). The conversion of acetyl-CoA into triglycerides (TGs) was promoted by ACC1. These TGs were transported from the hepatocytes to avoid the development of non-alcoholic fatty liver disease (NAFLD), causing a deficiency of acetyl-CoA in the liver, and then, the increased phosphorylated ACC2 promoted the cytoplasm fatty acids entering the mitochondria and conversion into acetyl-CoA through the fatty acid ß-oxidation pathway, causing a deficiency in fatty acids. Therefore, the liver showed enhanced absorption of exogenous fatty acids, which were converted into TGs, causing lipohyperplasia. In conclusion, an excessive IMP intake promotes metabolic dysfunction in adipose tissue.

Strain-level screening of human gut microbes identifies Blautia producta as a new anti-hyperlipidemic probiotic.

Compelling evidence has tightly linked gut microbiota with host metabolism homeostasis and inspired novel therapeutic potentials against metabolic diseases (e.g., hyperlipidemia). However, the regulatory profile of individual bacterial species and strain on lipid homeostasis remains largely unknown. Herein, we performed a large-scale screening of 2250 human gut bacterial strains (186 species) for the lipid-decreasing activity. Different strains in the same species usually displayed distinct lipid-modulatory actions, showing evident strain-specificity. Among the tested strains, Blautia producta exhibited the most potency to suppress cellular lipid accumulation and effectively ameliorated hyperlipidemia in high fat diet (HFD)-feeding mice. Taking a joint comparative approach of pharmacology, genomics and metabolomics, we identified an anteiso-fatty acid, 12-methylmyristic acid (12-MMA), as the key active metabolite of Bl. Producta. In vivo experiment confirmed that 12-MMA could exert potent hyperlipidemia-ameliorating efficacy and improve glucose metabolism via activating G protein-coupled receptor 120 (GPR120). Altogether, our work reveals a previously unreported large-scale lipid-modulatory profile of gut microbes at the strain level, emphasizes the strain-specific function of gut bacteria, and provides a possibility to develop microbial therapeutics against hyperlipidemia based on Bl. producta and its metabolite.

Multi-omics reveals 2-bromo-4,6-dinitroaniline (BDNA)-induced hepatotoxicity and the role of the gut-liver axis in rats.

2-Bromo-4, 6-dinitroaniline (BDNA) is a widespread azo-dye-related hazardous pollutant. However, its reported adverse effects are limited to mutagenicity, genotoxicity, endocrine disruption, and reproductive toxicity. We systematically assessed the hepatotoxicity of BDNA exposure via pathological and biochemical examinations and explored the underlying mechanisms via integrative multi-omics analyses of the transcriptome, metabolome, and microbiome in rats. After 28 days of oral administration, compared with the control group, 100 mg/kg BDNA significantly triggered hepatotoxicity, upregulated toxicity indicators (e.g., HSI, ALT, and ARG1), and induced systemic inflammation (e.g., G-CSF, MIP-2, RANTES, and VEGF), dyslipidemia (e.g., TC and TG), and bile acid (BA) synthesis (e.g., CA, GCA, and GDCA). Transcriptomic and metabolomic analyses revealed broad perturbations in gene transcripts and metabolites involved in the representative pathways of liver inflammation (e.g., Hmox1, Spi1, L-methionine, valproic acid, and choline), steatosis (e.g., Nr0b2, Cyp1a1, Cyp1a2, Dusp1, Plin3, arachidonic acid, linoleic acid, and palmitic acid), and cholestasis (e.g., FXR/Nr1h4, Cdkn1a, Cyp7a1, and bilirubin). Microbiome analysis revealed reduced relative abundances of beneficial gut microbial taxa (e.g., Ruminococcaceae and Akkermansia muciniphila), which further contributed to the inflammatory response, lipid accumulation, and BA synthesis in the enterohepatic circulation. The observed effect concentrations here were comparable to the highly contaminated wastewaters, showcasing BDNA's hepatotoxic effects at environmentally relevant concentrations. These results shed light on the biomolecular mechanism and important role of the gut-liver axis underpinning BDNA-induced cholestatic liver disorders in vivo.

Zearalenone-14-glucoside specifically promotes dysplasia of Gut-Associated Lymphoid Tissue: A natural product for constructing intestinal nodular lymphatic hyperplasia model.

INTRODUCTION: Zearalenone-14-glucoside (Z14G) is a modified mycotoxin that widely contaminates food across the world. Our preliminary experiment showed that Z14G degrades to zearalenone (ZEN) in the intestine exerting toxicity. Notably, oral administration of Z14G in rats induces intestinal nodular lymphatic hyperplasia. OBJECTIVES: To investigate the mechanism of Z14G intestinal toxicity and how it differs from ZEN toxicity. We conducted a precise toxicology study on the intestine of rats exposed to Z14G and ZEN using multi-omics technology. METHODS: Rats were exposed to ZEN (5 mg/kg), Z14G-L (5 mg/kg), Z14G-H (10 mg/kg), and pseudo germ free (PGF)-Z14G-H (10 mg/kg) for 14 days. Histopathological studies were performed on intestines from each group and compared. Metagenomic, metabolomic, and proteomic analyses were performed on rat feces, serum, and intestines, respectively. RESULTS: Histopathological studies showed that Z14G exposure resulted in dysplasia of gut-associated lymphoid tissue (GALT) compared to ZEN exposure. The elimination of gut microbes in the PGF-Z14G-H group alleviated or eliminated Z14G-induced intestinal toxicity and GALT dysplasia. Metagenomic analysis revealed that Z14G exposure significantly promoted the proliferation of Bifidobacterium and Bacteroides compared to ZEN. Metabolomic analysis showed that Z14G exposure significantly reduced bile acid, while proteomic analysis found that Z14G exposure significantly reduced the expression of C-type lectins compared to ZEN. CONCLUSIONS: Our experimental results and previous research suggest that Z14G is hydrolyzed to ZEN by Bifidobacterium and Bacteroides promoting their co-trophic proliferation. This leads to inactivation of lectins by hyperproliferative Bacteroides when ZEN caused intestinal involvement, resulting in abnormal lymphocyte homing and ultimately GALT dysplasia. It is noteworthy that Z14G is a promising model drug to establish rat models of intestinal nodular lymphatic hyperplasia (INLH), which is of great significance for studying the pathogenesis, drug screening and clinical application of INLH.

Gut microbiota and hypertension: association, mechanisms and treatment.

OBJECTIVES: Hypertension is one of the most important risk factors for cardio-cerebral vascular diseases, which brings a heavy economic burden to society and becomes a major public health problem. At present, the pathogenesis of hypertension is unclear. Increasing evidence has proven that the pathogenesis of hypertension is closely related to the dysbiosis of gut microbiota. We briefly reviewed relevant literature on gut microbiota and hypertension to summarize the relationship between gut microbiota and hypertension, linked the antihypertension effects of drugs with their modulation on gut microbiota, and discussed the potential mechanisms of various gut microbes and their active metabolites to alleviate hypertension, thus providing new research ideas for the development of antihypertension drugs. METHODS: The relevant literature was collected systematically from scientific database, including Elsevier, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Baidu Scholar, as well as other literature sources, such as classic books of herbal medicine. RESULTS: Hypertension can lead to gut microbiota imbalance and gut barrier dysfunction, including increased harmful bacteria and hydrogen sulfide and lipopolysaccharide, decreased beneficial bacteria and short-chain fatty acids, decreased intestinal tight junction proteins and increased intestinal permeability. Gut microbiota imbalance is closely related to the occurrence and development of hypertension. At present, the main methods to regulate the gut microbiota include fecal microbiota transplantation, supplementation of probiotics, antibiotics, diet and exercise, antihypertensive drugs, and natural medicines. CONCLUSIONS: Gut microbiota is closely related to hypertension. Investigating the correlation between gut microbiota and hypertension may help to reveal the pathogenesis of hypertension from the perspective of gut microbiota, which is of great significance for the prevention and treatment of hypertension.

Traditional Chinese medicines (TCMs) with varied meridians (Gui-Jing) differentially alleviate the adverse impact of Coptis chinensis on gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: The meridian (GuiJing) theory is a unique theory of traditional Chinese medicine (TCM) which has been guiding the clinical practice of TCM for thousands of years, but physiological foundation of TCM's meridian remains to be clarified. Recent investigations have marked gut microbiota as a key mediator for the pharmacological effects of various TCMs. However, most studies focus on the response of gut microbes to a single drug or formula, the interactive effects of different drugs on gut microbiota are scarcely investigated. AIM OF THE STUDY: In this work, we evaluated the co-regulatory effects of different TCMs on gut microbiota when they were individually combined with Coptis chinensis (HL), and assessed the relationship between gut microbiota and the GuiJing of TCMs. MATERIALS AND METHODS: Normal C57BL/6 mice were gavaged with HL extract for 14 days to disrupt the gut microbial community. Simultaneously, animals were treated with different TCMs which all possess antimicrobial activity but belong to different meridians. The gut microbiota was analyzed by full-length 16S rRNA gene amplicon sequencing to get a thorough bacterial profile at the species level. RESULTS: Administration of HL dramatically disrupted the gut microbiota and decreased the alpha diversity. Co-administration of different TCMs alleviated the adverse impact of HL on gut microbiota in a meridian-dependent manner. TCMs belonging to Shaoyin meridian moderately shifted the gut microbiota, while TCMs belonging to Taiyin and especially Jueyin meridians remarkably recovered the gut microbial community to the normal status. Decreased Firmicutes (Clostridia and Bacilli) and Actinobacteria (Bifidobacteriales) and increased Proteobacteria (Enterobacteriaceae) were main features of HL-induced gut dysbiosis. TCMs belonging to Shaoyin, Taiyin and Jueyin meridians gradually reversed the abundance of these bacteria to their normal levels. Simultaneously, the promoting effect of HL on beneficial bacteria such as Akkermansia muciniphila and Blautia coccoides was substantially preserved when co-administration of these TCMs, suggesting that co-treatment with these TCMs may reduce the toxicity of HL without deteriorating its beneficial effects. CONCLUSION: Combination of special TCMs may alleviate the adverse effect of HL on gut microbiota while preserving its beneficial actions. Gut microbiota may be a potential biological indicator of the meridian of TCMs.

The linkage of gut microbiota and the property theory of traditional Chinese medicine (TCM): Cold-natured and sweet-flavored TCMs as an example.

ETHNOPHARMACOLOGICAL RELEVANCE: The property theory of traditional Chinese medicine (TCM) is a unique medical theory based on an extensive clinical practice for thousands of years, which guides TCM doctors choosing proper medicines to treat specific diseases. The nature and flavor of TCM are a high generalization of drug's characteristics according to the property theory. Despite intensive investigations, the modern interpretation of TCM property theory still confronts several challenges, which greatly hampers the elucidation of TCM's mechanisms as well as its application. Compelling evidence has proved that gut microbiota may be a potential indicator for TCM's efficacy and mechanism. Nevertheless, at present, the relationship between the gut microbiota and the nature and flavor of TCM has not been fully elucidated. AIM OF THE STUDY: To fill the gap in this field, we developed a comprehensive study to investigate the relationship between gut microbial community and TCM's property. MATERIALS AND METHODS: We searched "PubMed" and "China National Knowledge Infrastructure (CNKI)" with the key word "gut microbiota", and screened the published articles related to TCM. In this review, we mainly applied cold-natured and sweet-flavored TCMs as an example to explore the modulation of cold-natured and sweet-flavored TCMs on gut microbiota, and identify the potential relationship between the alterations of gut microbiota and TCM's efficacy. RESULTS: We found cold-natured and sweet-flavored TCMs possess several pharmacological activities and generally enrich beneficial bacteria like Akkermansia, Bacteroides, Lactobacillus and Bifidobacterium, which is in good accordance with their pharmacological effects. Simultaneously, these TCMs reduce the relative abundance of some harmful bacteria belonging to Firmicutes (Streptpcoccus, Enterococcus, Turicibacter, Anaerostipes and Oscillibacter) and Proteobacteria (Helicobacter, Enterobacter, Sutterella, Klebsiella, Desulfovibrio, Escherichia coli and Campylobacter jejuni). These results indicate that there are some intrinsic correlations between gut microbiota and the property of TCM, and gut microbiota may serve as a potential indicator to reflect the property of TCM. CONCLUSIONS: This pilot but comprehensive review provides an interesting proposal that the ancient theory of TCM property may be interpreted by the modern biological findings in gut microbiome.

Gut microbiota combined with metabolites reveals unique features of acute myocardial infarction patients different from stable coronary artery disease.

INTRODUCTION: Acute myocardial infarction (AMI) accounts for the majority of deaths caused by coronary artery disease (CAD). Early warning of AMI, especially for patients with stable coronary artery disease (sCAD), is urgently needed. Our previous study showed that alterations in the gut microbiota were correlated with CAD severity. OBJECTIVES: Herein, we tried to discover accurate and convenient biomarkers for AMI by combination of gut microbiota and fecal/blood/urinary metabolomics. METHODS: We recruited 190 volunteers including 93 sCAD patients, 49 AMI patients, and 48 subjects with normal coronary artery (NCA), and measured their blood biochemical parameters, 16S rRNA-based gut microbiota and NMR-based fecal/blood/urinary metabolites. We further selected 20 subjects from each group and analyzed their gut microbiota by whole-metagenome shotgun sequencing. RESULTS: Multi-omic analyses revealed that AMI patients exhibited specific changes in gut microbiota and serum/urinary/fecal metabolites as compared to subjects with sCAD or NCA. Fourteen bacterial genera and 30 metabolites (11 in feces, 10 in blood, 9 in urine) were closely related to AMI phenotypes and could accurately distinguish AMI patients from sCAD patients. Some species belonging to Alistipes, Streptococcus, Ruminococcus, Lactobacillus and Faecalibacterium were effective to distinguish AMI from sCAD and their predictive ability was confirmed in an independent cohort of CAD patients. We further selected nine indicators including 4 bacterial genera, 3 fecal and 2 urinary metabolites as a noninvasive biomarker set which can distinguish AMI from sCAD with an AUC of 0.932. CONCLUSION: Combination of gut microbiota and fecal/urinary metabolites provided a set of potential useful and noninvasive predictive biomarker for AMI from sCAD.

Gut fungi differentially response to the antipyretic (heat-clearing) and diaphoretic (exterior-releasing) traditional Chinese medicines in Coptis chinensis-conditioned gut microbiota.

Antipyretic (heat-clearing) and diaphoretic (exterior-releasing) drugs are two main groups of traditional Chinese medicines (TCMs) possessing anti-microbes and anti-inflammation effects, with the former mainly through clearing pyrogens while the latter through promoting diaphoresis. Although anti-microorganism is a common action of these two kinds of TCMs, their difference in antimicrobial spectrums and their interactions when combinedly used remain unclear. Herein, we prepared aqueous extracts from Coptis chinensis (HL) and other antipyretic or diaphoretic TCMs, orally administrated them to C57BL/6 mice at a clinical dose for fourteen days, and analyzed their impaction on both gut bacteria and fungi using full-length 16 S rRNA gene sequencing and internal transcribed spacer 1/2 (ITS1/2) gene sequencing, respectively. Oral administration of HL significantly changed the structure of gut bacteria but showed little influence on gut fungi. Co-treatment with antipyretic or diaphoretic TCMs alleviated the impact of HL on gut bacteria to a similar degree. However, combined with either heat-clearing or exterior-releasing TCMs significantly strengthened the influence of HL on gut fungi, with the latter superior to the former. The antipyretic TCMs enriched Penicillium spp. while diaphoretic TCMs promoted Fusarium spp. Further analysis revealed that the diaphoretic TCMs-enriched fungi Fusarium spp. were positively related to Akkermansia spp., a beneficial bacterium that interacts with Toll-like receptor 4 (TLR4) and regulates thermogenesis, thus providing a potential linkage with their pro-diaphoresis effect. Together, our results reveal that gut fungi differentially respond to the impact of heat-clearing and exterior-releasing TCMs on Coptis chinensis-conditioned gut microbiota, which provides insights into their functional characteristics.

The Gut Microbial Co-Abundance Gene Groups (CAGs) Differentially Respond to the Flavor (Yao-Wei) of Chinese Materia Medica.

The property theory is a unique principle instructing traditional Chinese doctors to prescribe proper medicines against diseases. As an essential part of it, the five-flavor theory catalogs various Chinese materia medicas (CMMs) into five flavors (sweet, bitter, sour, salty, and pungent) based on their taste and medical functions. Although CMM has been successfully applied in China for thousands of years, it is still a big challenge to interpret CMM flavor via modern biomarkers, further deepening its elusiveness. Herein, to identify the correlation between gut microbiota and CMM flavor, we selected 14 CMMs with different flavors to prepare their aqueous extracts, quantified the contained major chemical components, and then performed full-length 16S rRNA sequencing to analyze the gut microbiota of C57BL/6 mice administrated with CMM extracts. We found that flavones, alkaloids, and saponins were the richest components for sweet-, bitter-, and pungent-flavored CMMs, respectively. Medicines with merged flavors (bitter-pungent and sweet-pungent) displayed mixed profiles of components. According to gut microbial analysis, modulation of CMMs belonging to the same flavor on the taxonomic classification was inconsistent to an extent, while the functional sets of gut microbiota, co-abundance gene groups (CAGs), strongly and differentially responded to distinct flavors. Moreover, these correlations were in line with their pharmacological actions. Therefore, the gut microbial functional sets (CAGs) could act as the possible indicator to reflect CMM flavor, rather than the composition of microbial community.

Adenosine-rich extract of Ganoderma lucidum: A safe and effective lipid-lowering substance.

Ganoderma lucidum is a traditional Chinese medicine with a variety of active compounds and possesses adequate lipid-lowering and anti-atherosclerotic effects. However, its main active components and potential mechanisms still remain unclear. Here, we evaluated the anti-hyperlipidemic effect of the adenosine extract from Ganoderma lucidum (AEGL) in high-fat-diet (HFD)-induced hyperlipidemic ApoE-/- mice and explored the underlying biological mechanism by multi-omics analysis. Treatment with AEGL for 8 weeks significantly decreased the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c) by 45.59%, 41.22%, and 39.02%, respectively, as well as reduced liver TC and TG by 44.15% and 76.23%, compared with the HFD-only group. We also observed significant amelioration of hepatic steatosis without liver and kidney damage after AEGL treatment. Regulating the expression and acetylation/crotonylation of proteins involved in the PPAR signaling pathway may be one of the potential mechanisms involved in the observed lipid-lowering effects of AEGL.

The berberine-enriched gut commensal Blautia producta ameliorates high-fat diet (HFD)-induced hyperlipidemia and stimulates liver LDLR expression.

Berberine (BBR) is an effective cholesterol-lowering drug. Although gut microbiota has been implicated in the pharmacological activities of BBR, little evidence exists on the specific species of gut microbiota involved in its therapeutic effects, nor on linking gut bacteria to its recognized hypercholesterolemia-alleviating mechanism-upregulation of the low-density lipoprotein receptor (LDLR) in the liver. The present study was performed to identify the specific species of gut microbiota involved in the anti-hyperlipdemic effect of BBR, and interpret its mechanism through linking the gut microbiota and LDLR. The BBR-enriched gut bacterial species were identified by whole genome shotgun sequencing. Pure cultured B. producta was orally administered to C57BL/6 mice to evaluate its anti-hyperlipdemic effect. The LDLR-upregulating effect of B. producta was evaluated both in vitro and in vivo. Orally administration of BBR (200 mg/kg) decreased serum and liver lipid levels in HFD-induced hyperlipidemic mice. Microbiome analysis indicated that Blautia was closely associated with BBR's lipid-modulating activities. Further analysis revealed that BBR selectively promoted the growth of Blautia producta. Orally treatment of HFD mice with live B. producta reduced obesity and alleviated hyperlipidemia. Notably, the B. producta significantly increased LDLR expression in the liver, and its spent culture supernatant upregulated the LDLR level and promoted LDL uptake by HepG2 cells. Simultaneously, B. producta also linked butyrate-producing and bile salt hydrolase (BSH)-inhibiting effect of BBR. The gut microbiota, especially B. producta, may confers the hypercholesterolemia-alleviating effects of berberine. B. producta represents a novel probiotic that may be used for the treatment of dyslipidemia.

Dual modulation of gut bacteria and fungi manifests the gut-based anti-hyperlipidemic effect of Coptidis Rhizoma.

Coptidis Rhizoma exhibits potent effects on ameliorating metabolic disease through modulation of gut bacteria. Gut fungi play a significant role on the homeostasis of the intestinal microecosystem and several types of metabolic disorders. Previous studies have mainly concentrated on the function of bacteria on the beneficial effects of Coptidis Rhizoma and its main component berberine, but whether gut fungi are linked to the improvement of glycolipid metabolism disorder of Coptidis Rhizoma is not clear. Here, the anti-hyperlipidemic effects of Coptidis Rhizoma was firstly confirmed in the high fat diet (HFD)-induced mice. The changes of gut fungi and bacteria of the mice treated with Coptidis Rhizoma and the interaction of intestinal fungi and bacteria were investigated. Coptidis Rhizoma significantly decreased serum lipids and inhibited the hepatic lipid accumulation in the HFD-fed mice. Mechanistically, Coptidis Rhizoma reduced the diversity of gut bacteria and fungi, meanwhile changed their composition. Fungus Aspergillus species (A. chevalieri, A. luteovirescens, A. oryzae, A. sp. F51) and Penicillium (P. expansum, P. janthinellum, P. sp. BAB-5649 and P. sp. GZU-BCECYN66-5) were decreased in Coptidis Rhizoma-treated group, while Tilletia bornmuelleri, Tilletia bromi were increased. Furthermore, there are complex association between intestinal fungi and bacteria. For example, fungus Aspergillus (Aspergillus chevalieri, Aspergillus luteovirescens, Aspergillus oryzae) was negative associated with bacterium Blautia coccoides, but positive associated with Lactobacillus (L. johnsonii, L. sparagasseri, L. taiwanensis, L. amylovorus). These results demonstrated that Coptidis Rhizoma might exhibit anti-hyperlipidemic effects through modulation of the intestinal bacteria and fungi composition, and regulation their interaction.

Marked shifts in gut microbial structure and neurotransmitter metabolism in fresh inmates revealed a close link between gut microbiota and mental health: A case-controlled study

Background/Objective: The gut microbiota plays a pivotal role in psychological health, but the mechanistic perspective between gut microbiome and mental health remains poorly understoodMethod: The present case-controlled study recruited 30 unimprisoned subjects and 31 inmates that had been detained in jail for no more than a month. The mental health status, gut microbiota and blood NH3, H2S, 5-hydroxy trptamine and dopamine levels were measured.Results: Compared with unimprisoned controls, the fresh inmates exhibited significantly higher scores on anxiety and depression. Both phylogenetic structure and functional genes of the gut microbiota markedly shifted in inmates. Inmates was more Bacteroides-dominated, while unimprisoned subjects were more Prevotella-dominated. Short-chain fatty acids (SCFAs)-producing genera were largely decreased in inmates and were negatively related to mental disorder scores, while Bacteroidetes and Proteobacteria were positive to anxiety and depression scores. Simultaneously, the inmates possessed reduced genes that participate in amino acids, carbohydrates and vitamin cofactors metabolism, but enriched genes that involved in the neurotransmitter-producing Shikimate pathway. Correlation analysis revealed that Anaerotruncus and Prevotella were negative to depression score, and Enterococcus was negative to anxiety score.Conclusions: Our results revealed potential link between gut microbiota and mental health, leading further support to the microbiota–gut–brain axis theory. (AU)

Marked shifts in gut microbial structure and neurotransmitter metabolism in fresh inmates revealed a close link between gut microbiota and mental health: A case-controlled study.

Background/Objective: The gut microbiota plays a pivotal role in psychological health, but the mechanistic perspective between gut microbiome and mental health remains poorly understood. Method: The present case-controlled study recruited 30 unimprisoned subjects and 31 inmates that had been detained in jail for no more than a month. The mental health status, gut microbiota and blood NH3, H2S, 5-hydroxy trptamine and dopamine levels were measured. Results: Compared with unimprisoned controls, the fresh inmates exhibited significantly higher scores on anxiety and depression. Both phylogenetic structure and functional genes of the gut microbiota markedly shifted in inmates. Inmates was more Bacteroides-dominated, while unimprisoned subjects were more Prevotella-dominated. Short-chain fatty acids (SCFAs)-producing genera were largely decreased in inmates and were negatively related to mental disorder scores, while Bacteroidetes and Proteobacteria were positive to anxiety and depression scores. Simultaneously, the inmates possessed reduced genes that participate in amino acids, carbohydrates and vitamin cofactors metabolism, but enriched genes that involved in the neurotransmitter-producing Shikimate pathway. Correlation analysis revealed that Anaerotruncus and Prevotella were negative to depression score, and Enterococcus was negative to anxiety score. Conclusions: Our results revealed potential link between gut microbiota and mental health, leading further support to the microbiota-gut-brain axis theory.