Regulating Gut Microbiota Research Articles

Histidine-derived carbon dots for redox modulation and gut microbiota regulation in inflammatory bowel disease therapy

Inflammatory bowel disease (IBD) is a chronic inflammation of the colon that is becoming increasingly prevalent. As a result, there is a growing demand for safe, effective, and non-addictive drugs. Herein, we are inspired by using carbon dots-based nanomedicines to regulate redox balance and alleviate inflammatory diseases. Specifically, histidine-derived carbon dots (His-CDs) with antioxidant and multi-enzyme (superoxide dismutase, catalase) activities are synthesized, which not only improve intestinal redox balance, but also demonstrate promising potential in modulating gut microbiota for the treatment of IBD. To understand that underlying activities mechanisms of His-CDs, their precursors, structures, and band gaps are carefully analyzed. Our investigations show that His-CDs effectively reduce oxidative damage to cells and nematodes by scavenging free radicals. Furthermore, we confirm the anti-IBD effects of His-CDs at both cellular and mouse levels. Importantly, our research reveal that His-CDs restore intestinal homeostasis in colitis by regulating the gut microbiota. We further validate this finding through fecal microbiota transplantation, which demonstrate an increase in the abundance of beneficial bacteria in the intestinal tract following the administration of His-CDs. This investigation not only expands the knowledge of nanozymes, but also offers a promising nanomedicine approach for IBD therapy.

Shen-Bai-Jie-Du decoction suppresses the progression of colorectal adenoma to carcinoma through regulating gut microbiota and short-chain fatty acids

BackgroundShen-Bai-Jie-Du decoction (SBJDD), a traditional Chinese herb formula developed based on evidence-based medicine, is efficacy to reduce the recurrence and carcinogenesis of colorectal adenoma. However, the mechanism of SBJDD to treat colorectal adenoma remains unclear. The present study aims to investigate the efficacy and mechanism of SBJDD on colorectal adenoma carcinogenesis from the aspects of regulating gut microbiota and short-chain fatty acids (SCFAs).MethodsTwenty-one patients diagnosed with colorectal adenoma were recruited in the study and required to take SBJDD for four consecutive weeks. Analysis of gut microbiota was conducted using 16S rRNA gene amplicon sequencing, while levels of SCFAs in fecal and serum samples were determined through HPLC–MS/MS. Additionally, twenty-four Apcmin/+ mice were randomly assigned to normal diet (ND), high-fat diet (HFD), and SBJDD groups. The pharmacological effects and mechanism of SBJDD on colorectal adenoma carcinogenesis were assessed using RT-qPCR, HE staining, IHC staining, Western blot, IF staining, and Flow cytometry assays.ResultsOur clinical study has shown that SBJDD can regulate the gut microbiota composition and enhance SCFAs production in patients with colorectal adenoma. SBJDD alleviated colorectal adenoma formation and carcinogenesis, as well as protected the integrity of the intestinal barrier in the Apcmin/+ mice model compared to the HFD group. Additionally, SBJDD was found to regulate gut microbiota capable of producing SCFAs. G protein-coupled receptors GPR43, GPR41, and GPR109a were effectively activated in the SBJDD group, while HDAC1 and HDAC3 were inhibited. Furthermore, decreased expression levels of interleukin 1 beta (IL-1β) and interleukin 6 (IL-6), along with elevated expression level of interleukin 10 (IL-10), were observed in the colorectal tissue of the SBJDD group. Finally, SBJDD exhibited the ability to reduce the proportion of M1-type macrophages while increasing the proportion of M2-type macrophages.ConclusionsOur study objectively demonstrated the pharmacological effects of SBJDD in inhibiting the progression of colorectal adenoma and investigated its mechanisms in terms of regulating gut microbiota, increasing SCFAs, and reducing colorectal inflammation.

Effects of fermented Arctium lappa L. root by Lactobacillus casei on hyperlipidemic mice

IntroductionThis study aimed to establish a fermentation system based on Lactobacillus casei (LC) and Arctium lappa L. root (AR) to investigate its effects. The objectives included comparing metabolite profiles pre- and post-fermentation using untargeted metabolomics and evaluating the impact of LC-AR in high-fat diet-induced hyperlipidemic mice.MethodsUntargeted metabolomics was used to analyze differences in metabolites before and after fermentation. In vitro antioxidant activity, liver injury, lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA expression were assessed. 16S rRNA sequencing was conducted to evaluate changes in gut microbiota composition.ResultsLC-AR exhibited stronger antioxidant activity and higher metabolite levels than AR. It also improved liver injury as well as better regulation of lipid levels, pro-inflammatory cytokine levels, and cholesterol-related mRNA. 16S rRNA analysis revealed that LC-AR decreased the Firmicutes/Bacteroidetes ratio, which correlated negatively with triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels.DiscussionThese findings suggest that LC-AR may serve as a promising functional food and drug raw material for improving hyperlipidemia, particularly through its beneficial effects on gut microbiota and lipid regulation.

FMT and TCM to treat diarrhoeal irritable bowel syndrome with induced spleen deficiency syndrome- microbiomic and metabolomic insights

BackgroundDiarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites.MethodsThe new borne rats were procured from SPF facility and separated as healthy (1 group) and IBS-D model ( 3 groups) rats were prepared articially using mother’s separation and senna leaf treatment. 2 groups of IBS-D models were further treated with TCM- shenling Baizhu decoction and FMT. The efficacy was evaluated by defecation frequency, bristol stool score, and intestinal tight junction proteins (occludin-1 and claudin-1) expression. Microbiomic analysis was conducted using 16 S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database.ResultsSignificant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P < 0.05) after treatment with FMT and TCM. FMT and TCM altered the gut microbiota and regulated the tryptophan metabolism, steroid hormone biosynthesis and glycerophospholipid metabolism of IBS-D rats with spleen deficiency syndrome.The microbial abundance were changed in each case e.g., Monoglobus, Dubosiella, and Akkermansia and othe metabolic profiles.ConclusionFMT and TCM treatment improved the intestinal barrier function by regulating gut microbiota and improved metabolic pathways in IBS-D with spleen deficiency syndrome.

Effects of Zeaxanthin on the Insulin Resistance and Gut Microbiota of High-Fat-Diet-Induced Obese Mice

Obesity-induced insulin resistance (IR) can precipitate metabolic disorders such as diabetes. Zeaxanthin, a crucial member of the carotenoid family, has been found to mitigate the damage caused by obesity. However, reports on the effects of zeaxanthin on obesity-induced IR are lacking. Our objective was to examine the metabolic regulatory impacts of zeaxanthin on mice subjected to a high-fat diet (HFD) that triggered IR and to explore their influence on gut microbiota regulation. This study constructed a mouse model of metabolic dysfunction caused by lipid-rich nutritional patterns to investigate physiological and biochemical indices, liver pathway expression, and the intestinal microbiota. The mechanisms by which zeaxanthin improved both IR and glucose metabolic disorders were elucidated. The results demonstrate that zeaxanthin effectively suppressed obesity. The fasting blood glucose, area under curve of oral glucose tolerance test and insulin tolerance test, and homeostatic model assessment–insulin resistance (HOMA-IR) indices in the HFDZEA group decreased by 14.9%, 25.2%, 28.9%, and 29.8%. Additionally, zeaxanthin improved the lipid metabolism and alleviated damage to the liver and pancreas while also activating the PI3K/Akt pathway, regulating hepatic gluconeogenesis and the glycogen metabolism. The number of OTUs in the HFDZEA group increased by 29.04%. Zeaxanthin improved the structure and profile of the gastrointestinal microbiome and enhanced its diversity, increasing probiotics abundance, decreasing pathogen abundance, and thereby ameliorating the dysbiosis of enteric microbial communities in rodents with obesity resulting from excessive fat consumption. The outcomes of our analysis provide a rational basis for advancing zeaxanthin-based nutritional products.

Pueraria Extract Ameliorates Alcoholic Liver Disease via the Liver-Gut-Brain Axis: Focus on Restoring the Intestinal Barrier and Inhibiting Alcohol Metabolism.

Alcoholic liver disease (ALD) is one of the causes of hepatocellular carcinoma, accompanied by intestinal leakage and microbial changes. Pueraria has protective effects on liver injury. The aim of this study was to investigate the mechanism of pueraria in the treatment of ALD. UPLC-Q/TOF-MS was used to analyze the composition of the pueraria extract (PUE). Acute and chronic ALD models were established to evaluate the antialcoholic and hepatoprotective effects of PUE. As a result, PUE treatment reduced the serum levels of ALT, AST, TC, and TG and inflammatory factors and alleviated liver inflammation and drunk state. PUE decreased the gene expression of ADH1 and the serum level of acetaldehyde (ACH) to inhibit the generation of ACH from ethanol metabolism, increased the gene level of ALDH2 to accelerate the decomposition of ACH, and thereby alleviated liver inflammation and intestinal barrier damage. Meanwhile, 16 S rDNA revealed that PUE altered the microbiota composition, reduced the amount of Proteobacteria and Desulfobacterota, and thus inhibited the generation of lipopolysaccharide and its downstream-like TLR4/MyD88/NF-κB pathway. PUE also increased the abundance of Bacteroides, Ruminococcus, and Prevotella and producted short-chain fatty acids to protect the intestinal wall. Treatment with fecal microbiota transplantation further confirmed that PUE gut microbiota dependently alleviated ALD. Therefore, PUE regulated gut microbiota and inhibited ethanol metabolism to alleviate ALD through the liver-gut-brain axis. It has good prospects in the future.

Queen Bee Larva, an Edible By-Product of Royal Jelly, Alleviate D-Galactose-Induced Aging in Mouse by Regulating Gut Microbiota Structure and Amino Acid Metabolism

Queen bee larva (QBL), as a by-product of royal jelly, is a kind of protein-rich edible insect. However, the development and utilization of QBL have been very limited for an extended period, resulting in considerable economic waste. Notably, QBL has substantial potential for anti-aging treatments; however, systematic studies have been scarce. The present study aimed to analyze the effects of freeze-dried QBL powder (QBLP) treatment in a D-galactose (D-gal)-induced-aging mouse and to explore the mechanisms. A behavioral test indicated that QBLP-treated mice had improved cognitive function and memory decline caused by aging compared to untreated aged mice. Furthermore, QBLP treatment improved organ index in aged mice and prevented pathological damage to the brain tissue. Concomitantly, treatment of D-gal-induced-aging mice with QBLP significantly reduced the oxidative damage of serum and increased the skin moisture content of aging mice. Finally, integrated analyses of the gut microbiota and the serum metabolome showed that QBLP supplementation altered the composition of the gut microbiota, enriched biochemical pathways associated with amino acid metabolism, and adjusted serum concentrations of beneficial free amino acids. Overall, QBLP can improve symptoms related to D-gal-induced aging in mice by regulating gut microbiota structure and amino acid metabolism.

Dietary supplementation with novel selenium-enriched Pichia kudriavzevii regulates gut microbiota and host metabolism in mice.

Insufficient selenium intake can lead to serious health problems. However, most research on the functional properties of selenium-enriched probiotics has focused on sub-health conditions or disease models, with limited studies involving healthy subjects. Additionally, previous research has primarily explored the direct effects of selenium itself, neglecting its influence on gut microbiota and metabolism. This study aimed to explore whether long-term intake of Pichia kudriavzevii enriched with selenium affected gut microbiota and host metabolism in mice and to identify microbiota and metabolites related to beneficial outcomes. Results demonstrated that selenium-enriched P. kudriavzevii (SeY) exhibited non-toxic properties, did not cause colon or liver damage, enhanced antioxidant capacity, and reduced inflammation in a selenium dose-dependent manner. Additionally, SeY supplementation significantly altered the gut microbiota. High-dose SeY (HSeY) elevated the abundance of beneficial bacteria such as Lactobacillus and suppressed harmful bacteria such as Eubacterium nodatum group, Prevotellaceae_NK3B31_group, and unclassified_f__Lachnospiraceae. Low-dose SeY (LSeY) increased the abundance of Faecalibaculum. The strain without enriched selenium exhibited higher levels of Akkermansia compared to selenium-enriched strains. Both strains, with or without enriched selenium, stimulated the production of short-chain fatty acids. Non-targeted metabolomics analysis revealed that HSeY treatment regulated various metabolic pathways, such as tryptophan metabolism, tyrosine metabolism, and arginine biosynthesis. LSeY treatment modulated tyrosine metabolism, secondary bile acid metabolism, bile secretion, and primary bile acid metabolism. P. kudriavzevii regulated the metabolism of purine, arginine, proline, and tryptophan. Our study highlights the promise of SeY supplementation in regulating host metabolism and the gut microbiota, offering insights into its implications for promoting health.

Pueraria lobata extract ameliorates D-GalN/LPS-induced liver injury through targeting TLR4/NF-κB signalling pathway and regulating gut microbiota

AbstractKudzu root (Pueraria lobata), known for its dual role as a medicinal herb and food ingredient, has proven anti-inflammatory and antioxidant properties. This study explored the effects of P. lobata extract (PLE) on D-galactose/lipopolysaccharide (D-GalN/LPS)-induced liver inflammation and oxidative stress in mice, along with its impact on gut microbiota. The in vivo studies indicated that PLE significantly reduced hepatic levels of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin-1β, and interleukin-6) and increased the anti-inflammatory cytokine interleukin-10. It also lowered serum aspartate aminotransferase and alanine aminotransferase activities, indicating reduced liver damage, and mitigated oxidative stress by decreasing malondialdehyde levels while restoring superoxide dismutase activity. Western blot analysis revealed that PLE inhibited the phosphorylation of NF-κB pathway proteins (p65 and IκB) and suppressed TLR4 expression, highlighting its role in this inflammatory pathway. Additionally, PLE ameliorated D-GalN/LPS-induced gut microbiota dysbiosis, reducing Proteobacteria abundance and promoting beneficial genera such as Lactobacillus, Bifidobacterium, and Akkermansia. These findings suggest that PLE protects against liver inflammation and oxidative stress, while improving gut microbiota composition, offering potential therapeutic strategies for liver-related diseases.

Rice Protein Peptides Alleviate Alcoholic Liver Disease via the PPARγ Signaling Pathway: Through Liver Metabolomics and Gut Microbiota Analysis.

Alcoholic liver disease (ALD) is the predominant type of liver disease worldwide, resulting in significant mortality and a high disease burden. ALD damages multiple organs, including the liver, gut, and brain, causing inflammation, oxidative stress, and fat deposition. In this study, we investigated the effects of rice protein peptides (RPP) on ALD in mice with a primary focus on the gut microbiota and liver metabolites. The results showed that administration of RPP significantly alleviated the symptoms of ALD in mice including adiposity, oxidative stress, and inflammation. The KEGG pathway shows that RPP downregulates the liver metabolite of capric acid and the metabolism of fatty acid biosynthesis compared with the MOD group. Mechanistically, RPP downregulated the PPARγ signaling pathway and suppressed the expression of fatty acid biosynthesis genes (FASN, ACC1, ACSL1, and ACSL3). Furthermore, two active peptides (YLPTKQ and PKLPR) with potential therapeutic functions for ALD were screened by Caco-2 cell modeling and molecular docking techniques. In addition, RPP treatment alleviates gut microbiota dysbiosis by reversing the F/B ratio, increasing the relative abundance of Alloprevotella and Alistipes, and upregulating the level of short-chain fatty acids. In conclusion, RPP alleviates ALD steatosis through the PPARγ signaling pathway by YLPTKQ and PKLPR and regulates gut microbiota.

Didymin Ameliorates Dextran Sulfate Sodium (DSS)-Induced Ulcerative Colitis by Regulating Gut Microbiota and Amino Acid Metabolism in Mice.

Background: Didymin is a dietary flavonoid derived from citrus fruits and has been shown to have extensive biological functions, especially anti-inflammatory effects, but its mechanism is unclear. The purpose of this study was to investigate the potential mechanism of didymin that alleviates ulcerative colitis. Methods and Results: Our results indicated that didymin could alleviate the symptoms of ulcerative colitis, as it inhibited the expressions of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Didymin also promoted the expressions of claudin-1 and zona occludens-1(ZO-1), which are closely related with restoring colon barrier function. Didymin also increased the abundance of Firmicutes and Verrucomicobiota, while decreasing the abundance of Bacteroidota and Proteobacteria. Meanwhile, didymin significantly altered the levels of metabolites related to arginine synthesis and metabolism, and lysine degradation in the colitis mice. Utilizing network pharmacology and molecular docking, our results showed that the metabolites L-ornithine and saccharin could interact with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB). In this in vitro study, L-ornithine could reduce the expressions of transcription factors STAT3 and NF-κB, and it also inhibited the expressions of IL-6 and IL-1β in the lipopolysaccharides (LPS) induced in RAW264.7 cells, while saccharin had the opposite effect. Conclusions: Taken together, didymin can regulate gut microbiota and alter metabolite products, which can modulate STAT3 and NF-κB pathways and inhibit the expressions of inflammatory factors and inflammatory response in the DSS-induced colitis mice.

Gut microbiota is involved in leptin-induced thermoregulation in Mongolian gerbil (Meriones unguiculatus).

Leptin is a hormone that secreted by adipocytes and may promote energy expenditure by increasing thermogenesis. Our previous studies have shown that thermo-transient receptor potentials (thermo-TRPs) and gut microbiota are associated with thermoregulation in Mongolian gerbils, which are characterized by relative high serum leptin concentrations. Here, we test whether leptin can stimulate non-shivering thermogenesis (NST) in Mongolian gerbils, and whether thermo-TRPs and gut microbiota are involved in leptin-induced thermogenesis. First, gerbils were given acute leptin treatment (ALT) with different doses. Results showed that ALT significantly increased the body temperature of gerbils and change the composition of gut microbiota. Moreover, ALT groups showed a trend towards increased expression of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT). Then, we investigated the effect of chronic leptin treatment (CLT) on gerbils. Surprisingly, CLT did not affect gerbils' food intake and body weight, but it significantly increased the body temperature at the end. Besides, CLT did not affect the expression of thermogenic markers in BAT, white adipose tissue (WAT) and skeletal muscle. However, CLT increased the expression of leptin receptors and TRPV2 in the small intestine and affected the composition of gut microbiota. Together, our data suggest leptin may increase body temperature by regulating gut microbiota. In conclusion, the Mongolian gerbils with serum hyperleptin is beneficial for adapting the cold living environments, and TRPV2 and gut microbiota are involved.

Arabinoxylan Alleviates Obesity by Regulating Gut Microbiota and Bile Acid Metabolism.

Overweight and obesity are major and increasingly global public health concern. High intake of dietary fiber is negatively correlated with obesity and obesity-related metabolic diseases. Here, we investigated the impact of arabinoxylan on obesity based on the modification of gut microecology. Arabionxylan reduced body weight and improved glucose metabolism, as well as intestinal barrier function and metabolic endotoxemia in obese mice. Supplementation with arabinoxylan increased the relative abundance of Prevotellaceae_UCG_001, Lachnospiraceae_NK4A136_group, Clostridia_UCG_014, Alistipes, Bacteroides, and Ruminococcus, which was associated with the upregulated 7α-dehydroxylation function and production of secondary bile acids (deoxycholic acid and lithocholic acid). The modification of gut microbiota by arabinoxylan also influenced the production of SCFAs, genistein, daidzein, indolelactic acid, and indoleacetic acid, contributing to the amelioration of obesity. Our study highlights the antiobesity effects of arabinoxylan through the modification of gut microbiota and the production of bioactive metabolites.

The influence of perilipin 5 deficiency on gut microbiome profiles in murine metabolic dysfunction-associated fatty liver disease (MAFLD) and MAFLD-hepatocellular carcinoma.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has emerged as the leading cause of hepatocellular carcinoma (HCC) worldwide. Over the years, Perilipin 5 (PLIN5) has been recognized as a key regulator of both MAFLD and HCC development. In our previous studies we demonstrated that deficiency in Plin5 reduces the severity of MAFLD and HCC in mice. Interestingly, it has been established that patients with MAFLD and HCC exhibit various changes in their gut microbiome profiles. The gut microbiome itself has been shown to play a role in modulating carcinogenesis and the immune response against cancer. Therefore, we conducted a study to investigate the alterations in fecal microbiome composition in wild type (WT) and Plin5-deficient (Plin5 -/-) mice models of MAFLD and MAFLD-induced HCC (MAFLD-HCC). We utilized 16S rRNA gene sequencing analysis to profile the composition of gut bacteria in fecal samples. Notably, we discovered that the absence of Plin5 alone is already associated with changes in gut microbiota composition. Moreover, feeding the mice a Western diet (WD) resulted in additional microbial alterations. Interestingly, Plin5 -/- animals exhibited an enrichment of the beneficial taxa Lactobacillus in both animal models. Our findings identify Plin5 as a major regulator of gut microbiota during the development of MAFLD and MAFLD-HCC.

Bacterial and clinical metabolic signatures and their interactions in obese patients post-bariatric surgery

BackgroundObesity is a growing health concern in China, closely linked to metabolic disorders such as type 2 diabetes. Laparoscopic Sleeve Gastrectomy (LSG) is effective in promoting weight loss and improving metabolic outcomes. Emerging evidence highlights the role of gut microbiota in metabolic regulation, yet the specific alterations in gut microbiota and their association with metabolic changes post-surgery in Chinese patients remain unclear. Understanding these shifts could provide key insights into optimizing treatment strategies for metabolic improvement following bariatric surgery.MethodsStool samples and clinical data were collected from 30 obese patients before and 6 months after surgery. The composition of the gut microbiota was analyzed through 16S rRNA sequencing, and Spearman correlation analysis was used to determine the association between gut microbiota and clinical indicators.ResultsThe analysis of 30 patients showed a significant decrease in Body Mass Index (BMI) (36.75 ± 4.09 kg/m2 vs 26.37 ± 3.47 kg/m2, p < 0.0001). Glucose metabolism, including Hemoglobin A1C levels, improved significantly (6.05 ± 0.96 vs 5.05 ± 0.25, p < 0.0001), and liver function as well as serum lipid levels were also notably improved. LSG increased the richness and composition of gut microbiota in obese patients post-surgery. These changes in gut microbiota were closely associated with improved clinical metabolic parameters.ConclusionLSG not only significantly reduces body weight while also alleviating metabolic syndrome and comorbidities by altering gut microbiota.

Mechanisms of Electroacupuncture in Alleviating Visceral Hypersensitivity in Post-Infectious Irritable Bowel Syndrome Mice: The Role of GDNF Signaling Pathway and Gut Microbiota.

Post-infectious irritable bowel syndrome (PI-IBS) is a functional bowel disease that develops following an acute gastrointestinal infection. Electroacupuncture (EA) can regulate the gut microbiota and alleviate visceral hypersensitivity. Glial cell-derived neurotrophic factor (GDNF) is a potential factor in visceral hypersensitivity reactions. The aim of this study was to explore whether EA could alleviate visceral hypersensitivity in PI-IBS by regulating gut microbiota through GDNF signaling. 2,4,6-trinitrobenzene sulfonic acid (TNBS) was used to induce visceral hypersensitivity in PI-IBS mice. Assessment of intestinal visceral sensitivity using the abdominal withdrawal reflex (CRD). 16S ribosomal RNA (16S rRNA) sequencing to profile the gut microbiome community. GDNF can exacerbate the imbalances of the gut microbiota and increase visceral hypersensitivity compared with the model group. Whereas EA treatment increases the richness and diversity of the gut microbiota, decreases differences among species and alleviates visceral sensitivity. EA can alleviate visceral hypersensitivity in PI-IBS by regulating the gut microbiota via GDNF signaling, providing new insights for mechanistic research on EA in PI-IBS treatment.

Structural characteristics of a purified Evodiae fructus polysaccharide and its gastroprotection and relevant mechanism against alcohol-induced gastric lesions in rats

Evodiae fructus polysaccharide (EFP) has been previously shown to protect against alcohol-induced gastric lesions. However, which and how active fractions in EFP exert gastroprotection remains unclear. This study aimed to characterize the structure of the purified fraction (EFP-2-1) of EFP, and investigate its gastroprotection and underlying mechanisms. EFP-2-1 was obtained through column chromatography, and was characterized using instrumental analytical techniques. Gastroprotective effect of EFP-2-1 was evaluated using alcohol-induced gastric lesions in rats, and its mechanism was explored through proteomics, metabolomics and diversity sequencing. Results showed that EFP-2-1 had a molecular weight of 7.3 kDa, and consisted mainly of rhamnose, galacturonic acid, galactose and arabinose. Its backbone contained HG and RG-I domains, and branched with →5)-α-l-Araf-(1→, α-l-Araf-(1→ and →4)-β-d-Galp-(1→ residues. EFP-2-1 reduced gastric lesions and the levels of MDA, TNF-α and IL-6, activated PPARγ, primarily altered protein digestion and absorption and bile secretion metabolic pathways, regulated gut microbiota like Faecalibaculum and Lachnoclostridium, and increased short-chain fatty acids production. Correlations were observed among the gut microbiota, metabolites and biochemical indexes influenced by EFP-2-1. These findings suggest that EFP-2-1 is an active fraction of EFP for protecting against alcohol-induced gastric lesions, which may be linked to PPARγ activation, gut microbiota and serum metabolism.

Quinoa ameliorates polycystic ovary syndrome via regulating gut microbiota through PI3K/AKT/mTOR pathway and autophagy

BackgroundPolycystic ovary syndrome (PCOS) is a unity of endocrine and metabolic disorders, associated with PI3K/AKT/mTOR, autophagy, and gut microbiota. Quinoa is a valuable food source, which contains rich minerals, unsaturated fatty acids, and has a positive modulating effect on metabolic diseases. However, its effects and potential mechanisms on PCOS have not been reported yet. Therefore, the purpose of this study is to investigate the effect of quinoa on PCOS rats by regulating PI3K/AKT/mTOR, autophagy, and gut microbiota.MethodsTen–week-old female Sprague-Dawley (SD) rats have received letrozole for 24 days for induction of PCOS and subsequently were treated with a quinoa diet for 8 weeks. Vaginal smears were used to analyze the estrous cycle of rats. Hormone and biochemical indexes were analyzed by kit assays and glucometer. The pathological changes of ovary, pancreas, duodenum and colon were observed by HE staining. PI3K, AKT, mTOR and autophagy-related proteins in the ovary and colon were measured by western blot and immunohistochemistry staining. Tight junction proteins in colon were measured by immunohistochemistry staining. 16 s rDNA sequencing was used to detect the changes of intestinal microbiota in rats. Network pharmacology and molecular docking were used to study the possible targets and mechanisms of quinoa on PCOS. Spearman correlation analysis was used to study the relationship between intestinal microbial abundance and hormone levels of PCOS rats at the phylum and genus level.ResultsQuinoa significantly improved estrous cycle and biochemical parameters of PCOS-like rats, and the pathological state of ovary, pancreas, duodenum and colon tissues. Especially, quinoa significantly regulated the expression of PI3K, AKT, mTOR and autophagy-related proteins in the ovary. Quinoa may repair the intestinal barrier by upregulating the expression of tight junction proteins in the colon, and regulate autophagy-related factors in colon. Additionally, quinoa increased the abundance of Lactobacillu, Bacteroides and Oscillospira, and decreased the Firmicutes/Bacteroidetes ratio and the Blautia, and Prevotella, reversing the dysregulation of the gut microbiota. Correlation analysis showed that there is a strong correlation between gut microbiota with significant changes in abundance and hormone related to PCOS.ConclusionOur result indicated that effect of quinoa on PCOS maybe associated with activation of the PI3K/AKT/mTOR signaling pathway, inhibition of autophagy, and regulation of intestinal flora.

Alleviation of colitis by honeysuckle MIR2911 via direct regulation of gut microbiota

Inflammatory bowel disease (IBD) is a group of chronic relapsing diseases associated with inflammatory disorders and microbial dysbiosis of the intestine. The use of traditional Chinese medicine (TCM) to treat colitis has the advantage of fewer side effects, but the molecular mechanism is not clear. Recently, miRNAs have been recognized as novel functional small molecules in plants that have regulatory effects on biological activities. This study mainly investigated the mechanism of action of MIR2911 from Honeysuckle, the main component of TCM preparations for colitis. The results demonstrated that MIR2911 can be absorbed through the diet and secreted within host small extracellular vesicles (sEVs), acting directly on intestinal bacteria, reducing the abundance of Escherichia-Shigella, and improving colitis symptoms. This study provides a new theoretical basis for the molecular mechanism of TCM therapy and identifies a potential new drug a new drug target for the treatment of colitis.

Gut Microbiome and Metabolome Alterations in Overweight or Obese Adult Population after Weight-Loss Bifidobacterium breve BBr60 Intervention: A Randomized Controlled Trial.

Probiotics, known for regulating gut microbiota, may aid those with overweight or obesity, but their mechanisms require more research. This study involved 75 overweight or obese young adults, randomly assigned to either a Bifidobacterium breve BBr60 (BBr60) group or a placebo group. Both groups received diet guidance and took either BBr60 (1 × 1010 CFU/day) or a placebo for 12 weeks. Researchers analyzed body composition, serum glucose, lipids, liver and kidney function, comprehensive metabolome, and intestinal homeostasis before and after the intervention. After 12 weeks, BBr60 significantly reduced weight and BMI compared to pretreatment levels and outperformed the placebo. The BBr60 group also showed improved blood biochemistry, with notably lower fasting blood glucose (FBG) levels than the placebo group (p < 0.05). Additionally, BBr60 influenced vital serum and fecal metabolites related to three amino acid metabolic pathways and regulated the bacteria Dialister, Klebsiella, and Bacteroides, which correlated strongly with serum metabolites. These findings indicate that BBr60 can safely and effectively regulate BMI, body weight, serum glucose, lipids, and liver function markers, which may involve BBr60's impact on key gut bacteria, which influence metabolites related to the valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and alanine, aspartate, and glutamate metabolism.