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Objective: This cross-sectional study aims to analyze the differences in gut flora between patients with epilepsy with and without cognitive impairment and normal subjects. Methods: One hundred patients with epilepsy who came to our hospital from 2020.12 to 2022.12 (epilepsy group) were selected, and another 100 family members of the patients were selected as the control group (control group). Patients with epilepsy were further classified by the MMSE scale into 62 patients with combined cognitive impairment (Yes group) and 38 patients without cognitive impairment (No group). Detection of gut flora in feces by 16 S rRNA high-throughput sequencing. Logistic regression was used to analyze risk factors for cognitive dysfunction in patients with epilepsy. Results: There were more significant differences in the structure and composition of the gut flora between patients in the epilepsy group and the control group, but no significant differences in diversity analysis (P > 0.05). Actinobacteriota, Faecalibacterium and Collinsella were significantly lower in the Yes group than in the No group (P < 0.05), and the Alpha diversity index was numerically slightly smaller than in the No group, with the PCoA analysis demonstrating a more dispersed situation in both groups. Five metabolic pathways, including glycolysis and heterolactic fermentation, were upregulated in the Yes group. LEfSe analysis showed that five groups of bacteria, including Coriobacteriaceae and Collinsella, were selected as marker species for the presence or absence of comorbid cognitive impairment. Of these, Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy combined with cognitive impairment. Conclusion: There was an imbalance in the gut flora of patients with epilepsy compared to healthy controls. The gut flora of patients with epilepsy with cognitive dysfunction differs significantly from that of patients without cognitive dysfunction. Collinsella, Oscillospirales, and Ruminococcaceae have a greater impact on epilepsy with cognitive dysfunction and can be used as an indicator for the observation of epilepsy with cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Follicular skin disorders, including hidradenitis suppurativa (HS), frequently coexist with systemic autoinflammatory diseases, such as inflammatory bowel disease (IBD) and its subtypes, Crohn's disease and ulcerative colitis. Previous studies suggest that dysbiosis of the human gut microbiome may serve as a pathogenic link between HS and IBD. However, the role of the microbiome (gut, skin, and blood) in the context of IBD and various follicular disorders remains underexplored. Here, we performed a systematic review to investigate the relationship between follicular skin disorders, IBD, and the microbiome. Of the sixteen included studies, four evaluated the impact of diet on the microbiome in HS patients, highlighting a possible link between gut dysbiosis and yeast-exclusion diets. Ten studies explored bacterial colonization and HS severity with specific gut and skin microbiota, including Enterococcus and Veillonella. Two studies reported on immunological or serological biomarkers in HS patients with autoinflammatory disease, including IBD, and identified common markers including elevated cytokines and T-lymphocytes. Six studies investigated HS and IBD patients concurrently. Our systematic literature review highlights the complex interplay between the human microbiome, IBD, and follicular disorders with a particular focus on HS. The results indicate that dietary modifications hold promise as a therapeutic intervention to mitigate the burden of HS and IBD. Microbiota analyses and the identification of key serological biomarkers are crucial for a deeper understanding of the impact of dysbiosis in these conditions. Future research is needed to more thoroughly delineate the causal versus associative roles of dysbiosis in patients with both follicular disorders and IBD. [ABSTRACT FROM AUTHOR]

Gut microecology, the complex community consisting of microorganisms and their microenvironments in the gastrointestinal tract, plays a vital role in maintaining overall health and regulating various physiological and pathological processes. Recent studies have highlighted the significant impact of gut microecology on the regulation of uric acid metabolism. Natural products, including monomers, extracts, and traditional Chinese medicine formulations derived from natural sources such as plants, animals, and microorganisms, have also been investigated for their potential role in modulating uric acid metabolism. According to research, The stability of gut microecology is a crucial link for natural products to maintain healthy uric acid metabolism and reduce hyperuricemia-related diseases. Herein, we review the recent advanced evidence revealing the bidirectional regulation between gut microecology and uric acid metabolism. And separately summarize the key evidence of natural extracts and herbal formulations in regulating both aspects. In addition, we elucidated the important mechanisms of natural products in regulating uric acid metabolism and secondary diseases through gut microecology, especially by modulating the composition of gut microbiota, gut mucosal barrier, inflammatory response, purine catalyzation, and associated transporters. This review may offer a novel insight into uric acid and its associated disorders management and highlight a perspective for exploring its potential therapeutic drugs from natural products. [ABSTRACT FROM AUTHOR]

Hypertensive disorders of pregnancy (HDP) are severe complications of pregnancy with high morbidity and are a major cause of increased maternal and infant morbidity and mortality. Currently, there is a lack of effective early diagnostic indicators and safe and effective preventive strategies for HDP in clinical practice, except for monitoring maternal blood pressure levels, the degree of proteinuria, organ involvement and fetal conditions. The intestinal microbiota consists of the gut flora and intestinal environment, which is the largest microecosystem of the human body and participates in material and energy metabolism, gene expression regulation, immunity regulation, and other functions. During pregnancy, due to changes in hormone levels and altered immune function, the intestinal microecological balance is affected, triggering HDP. A dysregulated intestinal microenvironment influences the composition and distribution of the gut flora and changes the intestinal barrier, driving beneficial or harmful bacterial metabolites and inflammatory responses to participate in the development of HDP and promote its malignant development. When the gut flora is dysbiotic and affects blood pressure, supplementation with probiotics and dietary fiber can be used to intervene. In this review, the interaction between the intestinal microbiota and HDP was investigated to explore the feasibility of the gut flora as a novel biomarker of HDP and to provide a new strategy and basis for the prevention and treatment of clinical HDP. [ABSTRACT FROM AUTHOR]

The role of Auricularia auricula polysaccharide (AP) in the regulation of glycolipid metabolism was investigated using a high-fat-diet-induced hyperlipidemic mouse model. In a further step, its potential mechanism of action was investigated using microbiome analysis and widely targeted lipidomics. Compared to high-fat mice, dietary AP supplementation reduced body weight by 13.44%, liver index by 21.30%, epididymal fat index by 50.68%, fasting blood glucose (FBG) by 14.27%, serum total cholesterol (TC) by 20.30%, serum total triglycerides (TGs) by 23.81%, liver non-esterified fatty acid (NEFA) by 20.83%, liver TGs by 20.00%, and liver malondialdehyde (MDA) by 21.05%, and increased liver glutathione oxidase (GSH-PX) activity by 52.24%, total fecal bile acid (TBA) by 46.21%, and fecal TG by 27.16%, which significantly regulated glucose and lipid metabolism. Microbiome analysis showed that AP significantly downregulated the abundance of the Desulfobacterota phylum, as well as the genii Desulfovibrio, Bilophila, and Oscillbacter in the cecum of hyperlipidemic mice, which are positively correlated with high lipid indexes, while it upregulated the abundance of the families Eubacterium_coprostanoligenes_group and Ruminococcaceae, as well as the genii Eubacterum_xylanophilum_group, Lachnospiraceae_NK4A136_group, Eubacterium_siraeum_group, and Parasutterella, which were negatively correlated with high lipid indexes. In addition, AP promoted the formation of SCFAs by 119.38%. Widely targeted lipidomics analysis showed that AP intervention regulated 44 biomarkers in metabolic pathways such as sphingolipid metabolism and the AGE-RAGE signaling pathway in the hyperlipidemic mice (of which 15 metabolites such as unsaturated fatty acids, phosphatidylserine, and phosphatidylethanolamine were upregulated, and 29 metabolites such as phosphatidylcholine, ceramide, carnitine, and phosphatidylinositol were downregulated), thereby correcting glucose and lipid metabolism disorders. [ABSTRACT FROM AUTHOR]

Abstract Objective This cross-sectional study aims to analyze the differences in gut flora between patients with epilepsy with and without cognitive impairment and normal subjects. Methods One hundred patients with epilepsy who came to our hospital from 2020.12 to 2022.12 (epilepsy group) were selected, and another 100 family members of the patients were selected as the control group (control group). Patients with epilepsy were further classified by the MMSE scale into 62 patients with combined cognitive impairment (Yes group) and 38 patients without cognitive impairment (No group). Detection of gut flora in feces by 16 S rRNA high-throughput sequencing. Logistic regression was used to analyze risk factors for cognitive dysfunction in patients with epilepsy. Results There were more significant differences in the structure and composition of the gut flora between patients in the epilepsy group and the control group, but no significant differences in diversity analysis (P > 0.05). Actinobacteriota, Faecalibacterium and Collinsella were significantly lower in the Yes group than in the No group (P

AbstractContext Yi-Shen-Hua-Shi (YSHS) is a traditional Chinese medicine that treats chronic kidney disease (CKD). However, its efficacy in reducing proteinuria and underlying mechanisms is unknown.Objective This single-center randomized controlled trial explored whether YSHS could improve proteinuria and modulate the gut microbiota.Materials and methods 120 CKD patients were enrolled and randomized to receive the renin-angiotensin-aldosterone system (RAAS) inhibitor plus YSHS (n = 56) or RAAS inhibitor (n = 47) alone for 4 months, and 103 patients completed the study. We collected baseline and follow-up fecal samples and clinical outcomes from participants. Total bacterial DNA was extracted, and the fecal microbiome was analyzed using bioinformatics.Results Patients in the intervention group had a significantly higher decrease in 24-h proteinuria. After 4 months of the YSHS intervention, the relative abundance of bacteria that have beneficial effects on the body, such as Faecalibacterium, Lachnospiraceae, Lachnoclostridium, and Sutterella increased significantly, while pathogenic bacteria such as the Eggerthella and Clostridium innocuum group decreased. However, we could not find these changes in the control group. Redundancy analysis showed that the decline in 24-h proteinuria during follow-up was significantly correlated with various taxa of gut bacteria, such as Lachnospiraceae and the Lachnoclostridium genus in the YSHS group. KEGG analysis also showed the potential role of YSHS in regulating glycan, lipid, and vitamin metabolism.Discussion and conclusion The YSHS granule reduced proteinuria associated with mitigating intestinal microbiota dysbiosis in CKD patients. The definite mechanisms of YSHS to improve proteinuria need to be further explored.Trial registration ChiCTR2300076136, retrospectively registered.

Aronia melanocarpa, a plant rich in anthocyanins, has been studied for its potential to regulate blood sugar and blood lipids, although the specific mechanism is not yet understood. This research aims to identify the differential bacterial flora and elucidate the mechanism by which it improves glucose and lipid metabolism disorders through 16S rDNA gene sequencing. The study reveals the protective effect of Aronia melanocarpa extract (AME) on liver damage in type 2 diabetic rats. Experimental results demonstrate that AME can effectively modulate the abundance of intestinal flora, reduce colon tissue damage, enhance the weight of diabetic rats, and lower levels of fasting blood sugar, low‐density lipoprotein (LDL), and triglycerides (TG). Additionally, liver morphology analysis shows that AME can effectively mitigate liver tissue structural damage in type 2 diabetic rats. In conclusion, AME regulates glucose and lipid metabolism by influencing intestinal flora, ultimately regulating glucose and lipid metabolism in type 2 diabetic rats. [ABSTRACT FROM AUTHOR]

Orally administered crocin rapidly and efficiently rescues depressive-like behaviors in depression models; however, crocin levels in the circulatory and central nervous systems are rather low. The underlying mechanism responsible for the inconsistency between pharmacokinetics and pharmacodynamics is unknown. To identify the active metabolites and clarify the underlying mechanisms, the pharmacokinetics and metabolic effects of the gut flora and hepatic and intestinal microsomes on crocin were examined, and the pharmacodynamics of crocin and its major metabolite, crocetin, were also evaluated in both normal and pseudo germ-free mice subjected to chronic social defeat stress. The results showed that oral administration of 300 mg/kg crocin significantly improved the depression-like behaviors of chronic social defeat stress mice, although the levels of crocin in the circulatory system were rather low (Cmax = 43.5 ± 8.6 μg/L; AUC = 151 ± 20.8 μg·h/L). However, the primary metabolite of crocetin was much more abundant in vivo (Cmax = 4662.5 ± 586.1 μg/L; AUC = 33,451.9 ± 3323.6 μg·h/L). Orally administered crocin was primarily metabolized into crocetin by the gut flora instead of hepatic or intestinal microsomal enzymes, and less than 10% of crocin was transformed into crocetin in the liver or intestinal microsomes. Inhibition of the gut flora dramatically reduced the production of and in vivo exposure to crocetin, and the rapid antidepressant effect of crocin disappeared. Moreover, crocetin showed rapid antidepressant effects similar to those of crocin, and the effects were independent of the gut flora. In conclusion, the metabolic transformation of crocin to crocetin primarily contributes to the rapid antidepressant effects of crocin and is dependent on the gut flora. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD), a condition which is chronic and characterized by immune imbalance, colitis exacerbation and intestinal inflammation. The gut microbiota mainly responsible for progression and development of IBD, influencing IBD susceptibility, intestinal inflammation and immune dysregulation. Dysbiosis, characterized by an imbalance in the gut microbial composition, is observed in IBD patients, with a decrease in beneficial bacteria from the Firmicutes phylum and an increase in pathogenic bacteria from the Proteobacteria phylum. Additionally, alterations in the gut mycobiome and virome have been implicated in IBD, impacting bacterial-host interactions and bacterial functions. Dietary patterns, such as Mediterranean and vegetarian diets, have shown promising effects in IBD management. These diets, rich in fruits, olive oil, whole grains, fish oil and vegetables, provide essential nutrients and support a healthy gut microbiota, which help in preventing dysbiosis and its associated pathogenesis. Probiotic supplementation has demonstrated efficacy in restoring gut microbiota balance and improving symptoms in IBD patients. Specific probiotic strains have been found to modulate the intestinal barrier, immune function and inflammation, offering potential therapeutic benefits. [ABSTRACT FROM AUTHOR]

To investigate the effects of rapeseed diacylglycerol oil (RDG) intake on lipid accumulation and metabolism in C57BL/6J mice, obese mice were fed a high-fat diet in which 45% of the total energy content came from RDG (RDGM group) or rapeseed triacylglycerol oil (RTGM group). This diet intervention was conducted for 12 weeks following the establishment of the obese mouse model. By the end of the experiment, the serum glucose levels of the mice in the RTGM and RDGM groups were 13.0 ± 1.3 mmol/L and 9.7 ± 1.5 mmol/L, respectively. Meanwhile, the serum triglyceride level in the RDGM group was 26.3% lower than that in the RTGM group. The weight-loss effect in the RDGM group was accompanied by a significant decrease in the white adipose tissue (WAT) index. The RDG intervention did not significantly change the antioxidant and anti-inflammatory properties of the rapeseed oil in vivo. The RDG diet improved the liver lipid metabolism abnormalities induced by a high-fat diet, leading to decreased liver damage index values (AST and ALT). Additionally, compared to that in the RTGM group, the expression of the adipogenic genes PPAR-γ and DGAT decreased in both the liver and intestine by 21.7% and 16.7% and by 38.7% and 47.2%, respectively, in the RDGM group. Further, most lipolytic genes in BAT showed no significant change after the RDG intervention. This implies that RDG regulates lipid metabolism by altering the expression of adipogenic genes in the liver, intestine, and adipose tissue, thereby reducing the accumulation of WAT. Furthermore, the RDG diet enhanced gut flora diversity, increasing the relative levels of unclassified Muribaculaceae and decreasing the levels of Dubosiella and Faecalibaculum in the mouse gut, potentially accelerating lipid metabolism. Thus, a three-month RDG diet intervention in obese mice exhibited benefits in regulating the somatotype, serum obesity-related indices, gut flora structure, and lipid metabolism in the adipose tissue, liver, and intestine. [ABSTRACT FROM AUTHOR]

Simple Summary: Persistent inflammation, immunosuppression, and catabolic syndrome (PICS) are the main causes of poor outcomes in patients transferred out of ICU. Hyaluronic acid has a potential function to alleviate PICS, and, as a widely accepted food additive, HA can be consumed through food products such as dairy products, greatly increasing patient medical compliance. This study evaluated the remission effect of PICS model mice after oral administration of HA with different molecular weights. The results showed a nonlinear relationship between HA molecular weight and its effect of intervention with symptoms in PICS mice and the high molecular weight HA (HMW-HA) was more effective in relieving symptoms in PICS model mice. Therefore, we believe that HMW-HA can be used to prepare functional foods for the purpose of intervening with PICS disease. Hyaluronic acid (HA) is a new functional food additive which has the potential to ameliorate persistent inflammation, immunosuppression and catabolism syndrome (PICS), but the biological effects of HA with various molecular weights differ dramatically. To systematically investigate the efficacy of HA in altering PICS symptoms, medium-molecular-weight (MMW) HA was specifically selected to test its intervention effect on a PICS mouse model induced by CLP through oral administration, with high-molecular-weight (HMW) and low-molecular-weight (LMW) HA also participating in the experimental validation process. The results of pathological observations and gut flora showed that MMW HA rapidly alleviated lung lesions and intestinal structural changes in PICS mice in the short term. However, although long-term MMW HA administration significantly reduced the proportions of harmful bacteria in gut flora, inflammatory responses in the intestines and lungs of PICS mice were significantly higher in the MMW HA group than in the HMW HA and LMW HA groups. The use of HMW HA not only rapidly reduced the mortality rate of PICS mice but also improved their grip strength and the recovery of spleen and thymus indices. Furthermore, it consistently promoted the recovery of lung and intestinal tissues in PICS mice, and it also assisted in the sustained restoration of their gut microbiota. These effects were superior to those of LMW HA and MMW HA. The experimental results indicate that HMW weight HA has the greatest potential to be an adjunct in alleviating PICS as a food additive, while the safety of other HAs requires further attention. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP), known for its rapid onset and significant incidence and mortality rates, presents a clinical challenge due to the limited availability of effective treatments and preventive measures. Anemarsaponin B (ASB) has emerged as a potential therapeutic agent, demonstrating capabilities in reducing immune inflammation, positioning it as a promising candidate for AP treatment. Methods: We investigated the effects of ASB on AP in mice, induced by caerulein and lipopolysaccharide (LPS). Peripheral blood samples were collected 24 h post-induction with caerulein to assess of key biomarkers including lipase, amylase, TNF-a, IL-1ß, IL-6, SOD, and GSH-Px. A range of techniques such as immunohistochemistry staining, immunofluorescence staining, Western blotting, and quantitative Polymerase Chain Reaction (q-PCR), were employed to measure the expression of critical genes. Additionally, pancreas samples from the mice were harvested for microbiome and metabolome sequencing, with the data analyzed to understand the impact of ASB on AP. Results: Our study revealed that, compared to the sham group, the AP group exhibited significantly higher serum levels of lipase, amylase, and cytokines, while levels of SOD and GSH Px were notably lower. Treatment with ASB led to a substantial decrease in the levels of lipase, amylase, and cytokines, and an increase in SOD and GSH-Px levels. q-PCR analysis of pancreatic histiocytes corroborated these serum findings. Hematoxylin and Eosin (H&E) staining indicated significant alterations in the pathological changes in the pancreas, lungs, and small intestine of the AP model due to ASB. Immunofluorescence assays demonstrated that ASB alleviated the apoptosis of pancreatic histiocytes in the AP model. Western Blot and histological analyses showed that ASB reduced the phosphorylation of TAK, p38, JNK, and ERK proteins, as well as the levels of TRAF6 protein in the AP model. Furthermore, metabolomic and gut microbiota analysis identified 27 differential metabolites and 34 differential species. The combined metabolome and microbiome analysis suggested an association between certain microbes (e.g., unclassified-Saprospiraceae and unclassified-Micavibrionales) and metabolites (e.g., LysoPE (0:0/20:0), PC (DiMe(13,5)/PGJ2)), and Heptanoic acid, indicating potential pathways through which ASB may exert its therapeutic effects in AP. Conclusions: ASB exhibits therapeutic efficacy in treating AP induced by caerulein combined with lipopolysaccharide (LPS), primarily through modulating the mitogenactivated protein kinase (MAPK) signaling pathway. This discovery offers fresh perspectives for AP drug development, underscoring the potential of targeting specific cellular pathways. Additionally, the intricate interplay observed between the gut microbiota and metabolites following ASB treatment highlights novel therapeutic targets, suggesting that manipulating the gut microbiome and metabolome could be a viable strategy in AP management. These findings pave the way for further research into comprehensive treatment approaches that incorporate both pharmacological intervention and microbiota modulation. [ABSTRACT FROM AUTHOR]

Enterococcus faecium B13, selected from fermentation chili, has been proven to promote animal growth by previous studies, but it belongs to opportunistic pathogens, so a comprehensive evaluation of its probiotic properties and safety is necessary. In this study, the probiotic properties and safety of B13 were evaluated at the genetic and phenotype levels in vitro and then confirmed in vivo. The genome of B13 contains one chromosome and two plasmids. The average nucleotide identity indicated that B13 was most closely related to the fermentation-plant-derived strain. The strain does not carry the major virulence genes of the clinical E. faecium strains but contains aac(6′)-Ii, ant (6)-Ia, msrC genes. The strain had a higher tolerance to acid at pH 3.0, 4.0, and 0.3% bile salt and a 32.83% free radical DPPH clearance rate. It can adhere to Caco-2 cells and reduce the adhesion of E. coli to Caco-2 cells. The safety assessment revealed that the strain showed no hemolysis and did not exhibit gelatinase, ornithine decarboxylase, lysine decarboxylase, or tryptophanase activity. It was sensitive to twelve antibiotics but was resistant to erythromycin, rifampicin, tetracycline, doxycycline, and minocycline. Experiments in vivo have shown that B13 can be located in the ileum and colon and has no adverse effects on experiment animals. After 28 days of feeding, B13 did not remarkable change the α-diversity of the gut flora or increase the virulence genes. Our study demonstrated that E. faecium B13 may be used as a probiotic candidate. [ABSTRACT FROM AUTHOR]

This study aimed to explore the mechanism of Xiaoyu Xiezhuo decoction (XXD) on ischemia–reperfusion-induced acute kidney injury (IRI-AKI) using network pharmacology methods and gut microbiota analysis. A total of 1778 AKI-related targets were obtained, including 140 targets possibly regulated by AKI in XXD, indicating that the core targets were mainly enriched in inflammatory-related pathways, such as the IL-17 signaling pathway and TNF signaling pathway. The unilateral IRI-AKI animal model was established and randomly divided into four groups: the sham group, the AKI group, the sham + XXD group, and the AKI + XXD group. Compared with the rats in the AKI group, XXD improved not only renal function, urinary enzymes, and biomarkers of renal damage such as Kim-1, cystatin C, and serum inflammatory factors such as IL-17, TNF-α, IL-6, and IL 1-β, but also intestinal metabolites including lipopolysaccharides, d-lactic acid, indoxyl sulfate, p-cresyl sulfate, and short-chain fatty acids. XXD ameliorated renal and colonic pathological injury as well as inflammation and chemokine gene abundance, such as IL-17, TNF-α, IL-6, IL-1β, ICAM-1, and MCP-1, in AKI rats via the TLR4/NF-κB/NLRP3 pathway, reducing the AKI score, renal pathological damage, and improving the intestinal mucosa’s inflammatory infiltration. It also repaired markers of the mucosal barrier, including claudin-1, occludin, and ZO-1. Compared with the rats in the AKI group, the α diversity was significantly increased, and the Chao1 index was significantly enhanced after XXD treatment in both the sham group and the AKI group. The treatment group significantly reversed this change in microbiota.

Driven by the good developmental potential and favorable environment at this stage, Ganoderma lucidum is recognized as a precious large fungus with medicinal and nutritional health care values. Among them, polysaccharides, triterpenoids, oligosaccharides, trace elements, etc. are important bioactive components in G. lucidum. These bioactive components will have an impact on gut flora, thus alleviating diseases such as hyperglycemia, hyperlipidemia and obesity caused by gut flora disorder. While numerous studies have demonstrated the ability of G. lucidum and its active components to regulate gut flora, a systematic review of this mechanism is currently lacking. The purpose of this paper is to summarize the regulatory effects of G. lucidum and its active components on gut flora in cardiovascular, gastrointestinal and renal metabolic diseases, and summarize the research progress of G. lucidum active components in improving related diseases by regulating gut flora. Additionally, review delves into the principle by which G. lucidum and its active components can treat or assist treat diseases by regulating gut flora. The research progress of G. lucidum in intestinal tract and its potential in medicine, health food and clinical application were fully explored for researchers. [ABSTRACT FROM AUTHOR]

Background: The incidence of comorbidity between type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) is high, and patients tend to be younger. When people develop metabolic diseases such as T2DM and MAFLD, the original homeostasis of the gut microbiota in the body is disrupted, and gut flora drift occurs. This study investigated the relationship between the number of gut flora and MAFLD in young-onset T2DM. Methods: This retrospective study analyzed 44 adolescent T2DM patients who were divided into a non-MAFLD group and a MAFLD group. Anthropometric measurements, clinical and biochemical markers, inflammatory markers, thyroid function assessments, and stool specimens were collected. Real-time PCR was performed to quantify several important gut flora constituents at the genus level. Student's t-test and the chi-square test were applied for group comparisons, and binary regression models were used to explore the relationship between gut flora and MAFLD in young-onset T2DM. Results: Among the 44 subjects, 26 (59.1%) were diagnosed with MAFLD, and 18 (40.9%) were not. Compared with the non-MAFLD group, body mass index (BMI), abdominal circumference, and levels of blood uric acid and thyroid stimulating hormone (TSH) in the MAFLD group were significantly increased, and age level and high-density lipoprotein cholesterol (HDL-C) were significantly decreased (p < 0.05). Compared with the non-MAFLD group, the abundance of Faecalibacterium prausnitzii and Bifidobacterium in the MAFLD group was significantly reduced, and the abundance of Enterococcus and Lactobacillus was significantly increased (p < 0.05). In the multivariate regression analysis, Faecalibacterium prausnitzii and Bifidobacterium were independent protective factors for MAFLD in young-onset T2DM, after excluding confounding factors. Conclusion: In young-onset T2DM, there was a difference in gut flora between patients with MAFLD and those without MAFLD. Faecalibacterium prausnitzii and Bifidobacterium were independent protective factors for MAFLD in young-onset T2DM. [ABSTRACT FROM AUTHOR]

Our previous study found that feeding with Lactobacillus plantarum Ep-M17 could effectively affect the growth performance, immune response, and gut microbiota of Penaeus vannamei. However, high temperature and pressure during feed pelletizing is the main problem that can lead to a decrease in the activity of probiotics or cause their inactivation. Further investigation needs to investigate whether inactivated Ep-M17 can exert similar effects as live Ep-M17. Therefore, we evaluated the effects of inactivated L. plantarum Ep-M17 on growth performance, immune response, disease resistance, and gut microbiota in P. vannamei. Results show that adding inactivated Ep-M17 to the feed also promoted body weight gain and increased relative immune protection in shrimp. Also, histological examination revealed that the administration of inactivated Ep-M17 led to improvements in the density and distribution of microvilli in the intestines and enhancements in the abundance of B and R cells in the hepatopancreas. Additionally, the inactivated Ep-M17 supplementation resulted in increased activity levels of nutrient immune-related enzymes in both the shrimp hepatopancreas and intestines. Moreover, it stimulated the expression of Lvlec, PEN-3a, Crustin, LGBP, Lysozyme, and proPo genes in both the hepatopancreas and intestines. Furthermore, the inactivated Ep-M17 also increased bacterial diversity in the gut of shrimp and promoted the abundance of specific flora, facilitating the host organism's metabolism and immunity to improve the disease resistance of shrimp. Therefore, supplementation of inactivated L. plantarum Ep-M17 in shrimp diets can exert similar effects as live L. plantarum Ep-M17 effectively improving growth performance, gut microbiota, immune response, and disease resistance in P. vannamei. [ABSTRACT FROM AUTHOR]

Recent evidence suggests the anti‐inflammatory effect of carrageenan oligosaccharides (COS). The effects of COS on intestinal injury induced by 0.6% sodium dodecyl sulfate (SDS) and the molecular mechanisms involved were investigated in this study. 0.625, 1.25, and 2.5 mg/mL COS in diet had no toxic effect in flies, and they could all prolong SDS‐treated female flies' survival rate. 1.25 mg/mL COS prevented the development of inflammation by improving the intestinal barrier integrity and maintaining the intestinal morphology stability, inhibited the proliferation of intestine stem cells (ISCs), and the production of lysosomes induced by SDS, accompanied by a decrease in the expression of autophagy‐related genes. Moreover, COS decreased the active oxygen species (ROS) content in gut and increased the antioxidant activity in SDS‐induced female flies, while COS still played a role in increasing survival rate and decreasing intestinal leakage in CncC‐RNAi flies. The improvement of anti‐inflammation capacity may be associated with the regulation of intestinal microflora with COS supplementation for Drosophila melanogaster. COS changed the gut microbiota composition, and COS had no effect on germ‐free (GF) flies. It is highlighted that COS could not work in Relish‐RNAi flies, indicating relish is required for COS to perform beneficial effects. These results provide insights into the study of gut microbiota interacting with COS to modulate intestinal inflammation in specific hosts. [ABSTRACT FROM AUTHOR]

Purpose of Review: The importance of the gut microbiome has received increasing attention in recent years. New literature has revealed significant associations between gut health and various orthopedic disorders, as well as the potential for interventions targeting the gut microbiome to prevent disease and improve musculoskeletal outcomes. We provide a broad overview of available literature discussing the links between the gut microbiome and pathogenesis and management of orthopedic disorders. Recent Findings: Human and animal models have characterized the associations between gut microbiome dysregulation and diseases of the joints, spine, nerves, and muscle, as well as the physiology of bone formation and fracture healing. Interventions such as probiotic supplementation and fecal transplant have shown some promise in ameliorating the symptoms or slowing the progression of these disorders. Summary: We aim to aid discussions regarding optimization of patient outcomes in the field of orthopedic surgery by providing a narrative review of the available evidence-based literature involving gut microbiome dysregulation and its effects on orthopedic disease. In general, we believe that the gut microbiome is a viable target for interventions that can augment current management models and lead to significantly improved outcomes for patients under the care of orthopedic surgeons. [ABSTRACT FROM AUTHOR]

Aims: Type 2 Diabetes is intrinsically linked to cardiovascular disease (CVD) via diabetic dyslipidemia, both of which remain global health concerns with annually increasing prevalence. Given the established links between gut microbiome dysbiosis and metabolic diseases, its modulation is an attractive target to ameliorate metabolic imbalances in such patients. There is a need to quantitively summarise, analyse, and describe future directions in this field. Methods: We conducted a systematic review, meta‐analysis, and meta‐regression following searches in major scientific databases for clinical trials investigating the effect of pro/pre/synbiotics on lipid profile published until April 2022. Data were pooled using random‐effects meta‐analysis and reported as mean differences with 95% confidence intervals (CIs). PROSPERO No. CRD42022348525. Results: Data from 47 trial comparisons across 42 studies (n = 2692) revealed that, compared to placebo/control groups, the administration of pro/pre/synbiotics was associated with statistically significant changes in total cholesterol (−9.97 mg/dL [95% CI: −15.08; −4.87], p < 0.0001), low‐density lipoprotein (−6.29 mg/dL [95% CI: −9.25; −3.33], p < 0.0001), high‐density lipoprotein (+3.21 mg/dL [95% CI: 2.20; 4.22], p < 0.0001), very‐low‐density lipoprotein (−4.52 mg/dL [95% CI: −6.36; −2.67], p < 0.0001) and triglyceride (−22.93 mg/dL [95% CI: −33.99; −11.87], p < 0.001). These results are influenced by patient characteristics such as age or baseline BMI, and intervention characteristics such as dosage and duration. Conclusions: Our study shows that adjunct supplementation with a subset of pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and has the potential to reduce CVD risk. However, widespread inter‐study heterogeneity and the presence of several unknown confounders limit their adoption in clinical practice; future trials should be designed with these in mind. [ABSTRACT FROM AUTHOR]

Background: Rujin Jiedu decoction (RJJDD) is a classical prescription of Traditional Chinese Medicine that has long been applied to treat pneumonia caused by external infection, but whether and how it benefits influenza virus therapy remains largely unclear. The aim of this study was to investigate the anti-inflammatory effect of RJJDD on the mouse model of influenza and to explore its potential mechanism. Methods: The mice were mock-infected with PBS or infected with PR8 virus followed by treatment with RJJDD or antiviral oseltamivir. The weight loss and morbidity of mice were monitored daily. Network pharmacology is used to explore the potential pathways that RJJDD may modulate. qRT-PCR and ELISA were performed to assess the expression of inflammatory cytokines in the lung tissue and macrophages. The intestinal feces were collected for 16S rDNA sequencing to assess the changes in gut microbiota. Results: We demonstrate that RJJDD protects against IAV-induced pneumonia. Comprehensive network pharmacology analyses of the Mass Spec-identified components of RJJDD suggest that RJJDD may act through down-regulating key signaling pathways producing inflammatory cytokines, which was experimentally confirmed by cytokine expression analysis in IAV-infected mouse lung tissues and IAV single-strand RNA mimic R837-induced macrophages. Furthermore, gut microbiota analysis indicates that RJJDD prevented IAV-induced dysbiosis of host intestinal flora, thereby offering a mechanistic explanation for RJJDD's efficacy in influenza pneumonia. Conclusion: This study defines a previously uncharacterized role for RJJDD in protecting against influenza likely by maintaining homeostasis of gut microbiota, and provides a new therapeutic option for severe influenza.

ABSTRACT: Stress is known to disrupt the intestinal barrier and induce intestinal dysfunction. A critical role for gonadotropin inhibitory hormone (GnIH) in stress has emerged. However, whether GnIH mediates stress-induced intestinal dysfunction remains unknown. The present study explored this question through in vivo and in vitro experiments in hens. Our in vivo experiments showed that continuous intraperitoneal injection of GnIH not only significantly increased the concentration of stress hormones in serum, but also significantly elevated the mRNA expression of glucocorticoid receptor (GR) in the duodenum and jejunum. Moreover, morphological and molecular analyses revealed that GnIH disrupted the physical and chemical barriers of the intestine and dramatically increased inflammatory factor levels in the intestine and serum of hens. Interestingly, the microbiomics results showed that GnIH altered the structure and composition of the gut flora in the cecum, revealing an increased abundance of harmful intestinal bacteria such as Desulfovibrionaceae. Similar results were found in in vitro studies in which the GnIH-induced intestinal mucosal barrier was disrupted, and inflammation increased in jejunal explants, although no significant difference was found in the expression of GR between the control and GnIH groups. Our results demonstrated that GnIH not only directly damaged intestinal barriers and elevated intestinal inflammation but also mediated stress and microflora imbalance-induced intestinal function disorder, suggesting that GnIH is a potential therapeutic target for gut dysfunction, stress-induced intestinal function disorder, and inflammatory bowel disease in animals and humans.

Microplastics (MPs), which are prevalent and increasingly accumulating in aquatic environments. Other pollutants coexist with MPs in the water, such as pesticides, and may be carried or transferred to aquatic organisms, posing unpredictable ecological risks. This study sought to assess the adsorption of lambda-cyhalothrin (LCT) by virgin and aged polyethylene MPs (VPE and APE, respectively), and to examine their influence on LCT's toxicity in zebrafish, specifically regarding acute toxicity, oxidative stress, gut microbiota and immunity. The adsorption results showed that VPE and APE could adsorb LCT, with adsorption capacities of 34.4 mg∙g−1 and 39.0 mg∙g−1, respectively. Compared with LCT exposure alone, VPE and APE increased the acute toxicity of LCT to zebrafish. Additionally, exposure to LCT and PE-MPs alone can induce oxidative stress in the zebrafish gut, while combined exposure can exacerbate the oxidative stress response and intensify intestinal lipid peroxidation. Moreover, exposure to LCT or PE-MPs alone promotes inflammation, and combined exposure leads to downregulation of the myd88-nf-κb related gene expression, thus impacting intestinal immunity. Furthermore, exposure to APE increased LCT toxicity to zebrafish more than VPE. Meanwhile, exposure to PE-MPs and LCT alone or in combination has the potential to affect gut microbiota function and alter the abundance and diversity of the zebrafish gut flora. Collectively, the presence of PE-MPs may affect the toxicity of pesticides in zebrafish. The findings emphasize the importance of studying the interaction between MPs and pesticides in the aquatic environment.

Abstract Background The pathogenesis of cardiac arrhythmias is multifaceted, encompassing genetic, environmental, hemodynamic, and various causative factors. Emerging evidence underscores a plausible connection between gut flora, serum metabolites, and specific types of arrhythmias. Recognizing the role of host genetics in shaping the microbiota, we employed two-sample Mendelian randomization analyses to investigate potential causal associations between gut flora, serum metabolites, and distinct arrhythmias. Methods Mendelian randomization methods were deployed to ascertain causal relationships between 211 gut flora, 575 serum metabolites, and various types of arrhythmias. To ensure the reliability of the findings, five complementary Mendelian randomization methods, including inverse variance weighting methods, were employed. The robustness of the results was scrutinized through a battery of sensitivity analyses, incorporating the Cochran Q test, leave-one-out test, and MR-Egger intercept analysis. Results Eighteen gut flora and twenty-six serum metabolites demonstrated associations with the risk of developing atrial fibrillation. Moreover, ten gut flora and fifty-two serum metabolites were linked to the risk of developing supraventricular tachycardia, while eight gut flora and twenty-five serum metabolites were associated with the risk of developing tachycardia. Additionally, six gut flora and twenty-one serum metabolites exhibited associations with the risk of developing bradycardia. Conclusion This study revealed the potential causal relationship that may exist between gut flora, serum metabolites and different cardiac arrhythmias and highlights the need for further exploration. This study provides new perspectives to enhance diagnostic and therapeutic strategies in the field of cardiac arrhythmias.

The role of Auricularia auricula polysaccharide (AP) in the regulation of glycolipid metabolism was investigated using a high-fat-diet-induced hyperlipidemic mouse model. In a further step, its potential mechanism of action was investigated using microbiome analysis and widely targeted lipidomics. Compared to high-fat mice, dietary AP supplementation reduced body weight by 13.44%, liver index by 21.30%, epididymal fat index by 50.68%, fasting blood glucose (FBG) by 14.27%, serum total cholesterol (TC) by 20.30%, serum total triglycerides (TGs) by 23.81%, liver non-esterified fatty acid (NEFA) by 20.83%, liver TGs by 20.00%, and liver malondialdehyde (MDA) by 21.05%, and increased liver glutathione oxidase (GSH-PX) activity by 52.24%, total fecal bile acid (TBA) by 46.21%, and fecal TG by 27.16%, which significantly regulated glucose and lipid metabolism. Microbiome analysis showed that AP significantly downregulated the abundance of the Desulfobacterota phylum, as well as the genii Desulfovibrio, Bilophila, and Oscillbacter in the cecum of hyperlipidemic mice, which are positively correlated with high lipid indexes, while it upregulated the abundance of the families Eubacterium_coprostanoligenes_group and Ruminococcaceae, as well as the genii Eubacterum_xylanophilum_group, Lachnospiraceae_NK4A136_group, Eubacterium_siraeum_group, and Parasutterella, which were negatively correlated with high lipid indexes. In addition, AP promoted the formation of SCFAs by 119.38%. Widely targeted lipidomics analysis showed that AP intervention regulated 44 biomarkers in metabolic pathways such as sphingolipid metabolism and the AGE-RAGE signaling pathway in the hyperlipidemic mice (of which 15 metabolites such as unsaturated fatty acids, phosphatidylserine, and phosphatidylethanolamine were upregulated, and 29 metabolites such as phosphatidylcholine, ceramide, carnitine, and phosphatidylinositol were downregulated), thereby correcting glucose and lipid metabolism disorders.

Background: The pathogenesis of cardiac arrhythmias is multifaceted, encompassing genetic, environmental, hemodynamic, and various causative factors. Emerging evidence underscores a plausible connection between gut flora, serum metabolites, and specific types of arrhythmias. Recognizing the role of host genetics in shaping the microbiota, we employed two-sample Mendelian randomization analyses to investigate potential causal associations between gut flora, serum metabolites, and distinct arrhythmias. Methods: Mendelian randomization methods were deployed to ascertain causal relationships between 211 gut flora, 575 serum metabolites, and various types of arrhythmias. To ensure the reliability of the findings, five complementary Mendelian randomization methods, including inverse variance weighting methods, were employed. The robustness of the results was scrutinized through a battery of sensitivity analyses, incorporating the Cochran Q test, leave-one-out test, and MR-Egger intercept analysis. Results: Eighteen gut flora and twenty-six serum metabolites demonstrated associations with the risk of developing atrial fibrillation. Moreover, ten gut flora and fifty-two serum metabolites were linked to the risk of developing supraventricular tachycardia, while eight gut flora and twenty-five serum metabolites were associated with the risk of developing tachycardia. Additionally, six gut flora and twenty-one serum metabolites exhibited associations with the risk of developing bradycardia. Conclusion: This study revealed the potential causal relationship that may exist between gut flora, serum metabolites and different cardiac arrhythmias and highlights the need for further exploration. This study provides new perspectives to enhance diagnostic and therapeutic strategies in the field of cardiac arrhythmias. [ABSTRACT FROM AUTHOR]

Diabetes mellitus' complications are serious and the common treatment drugs have many side effects. Therefore, research on new methods of lowering blood sugar is urgent. Chickpeas have a significant hypoglycemic effect and can be combined with lactic acid bacteria fermentation to improve quality. It is hoped to develop new functional foods. This study was to investigate the effect of Lactobacillus and chickpea on the control of diabetic mice based on their modulating effect on intestinal flora. 48 4-week-old male SPF mice were evenly divided into four groups including one normal control group (CN) and three diabetes experimental groups that were established by intraperitoneal injection of streptozotocin after 8 weeks of high-sugar and high-fat rearing. The experimental groups were continuously fed with high-sugar and high-fat food and were divided into non-intervention group (DM), unfermented chickpea milk group (CM), and fermented chickpea milk group (FCM). The activity, spirit, and appearance of the mice were recorded daily, and fasting blood glucose and body weight were measured weekly. At the end of the experiment, blood and organ samples were collected, and the intestinal flora in mouse feces was analyzed to assess the effect of chickpea milk on intestinal flora using Operational Taxonomic Units Clustering (OTUs) and species classification analysis. The results showed that CN group demonstrated excellent mental status, while DM group demonstrated reduced mental status. The mice were characterized by the typical symptoms of diabetes mellitus. Compared with the DM group, the intervention groups (CM and FCM) showed improved mental status and activity, closer to normal hair condition, less moist under pads, and reduced odor. Through the 6-week intervention period, the blood glucose level stabilized at around 7.0 mmol/L in CN group and above 23.0 mmol/L in the DM group. The abundances of mucinophilic Eckermannia in CN, DM, CM, and FCM groups were 9.7%, 6.1%, 9.0%, and 12.3%, respectively. The results showed that Lactobacillus fermented chickpea milk possessed effective intervention on the intestinal flora of diabetic mice, which provided guidance for effective intervention and care in the clinic. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to collect and assess the evidence available on the effect of non nutritive sweeteners on appetite, weight and glycemic regulation. As a replacement for sugars, non-nutritive sweeteners (NNSs) are widely being used in different food products with the assumption that these would lower calorie intake and help to manage weight and blood sugar levels better. However, studies using animal models have reported that chronic exposure to NNSs leads to increased food consumption, weight gain and insulin resistance. Design/methodology/approach: Evidence was acquired from systematic reviews or meta-analyses (2016–2021) of relevant clinical studies, especially randomized control trials using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Findings: The review showed NNSs exposure did not conclusively induce increased food intake or change in subjective appetite ratings. Appetite biomarkers like ghrelin, gastric inhibitory peptide, C-peptide levels and Peptide YY remained mostly unaffected by NNSs. Meta-analyses of human randomized control studies showed a reduced energy intake and body weight. No significant change was seen in blood glucose levels, post-prandial glycemic or insulin response after consumption of NNSs. Adequate evidence is not available to conclusively say that NNSs influence gut health at doses relevant to human use. Research limitations/implications: Most studies which are prospective cohort, observational and cross-sectional studies suggest that use of NNSs may promote obesity and metabolic syndrome in adults. Such studies are plagued by confounding variables and reverse causation. Mechanistic evidence is mostly based on in-vitro and in-vivo studies. The same causal pathways may not be operative or relevant in humans. Practical implications: This review of available literature concludes that to achieve specific public health and clinical goals, the safe use of NNSs for the reduction of intakes of free sugars and energy should be explored. This would be possible by educating the consumer about energy compensation and understanding the nutritional content of artificially sweetened products in terms of calories coming from fat and complex carbohydrates used in the product. Originality/value: This study was, thus, designed with the objective of examining the usefulness of NNSs in human population, especially with respect to insulin regulation, glycemic control and weight management. Well-designed randomized control trials which control for confounding variables are needed to generate high quality evidence. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurodegenerative disease. Numerous investigations have demonstrated that medications that regulate the "brain–gut" axis can ameliorate disease symptoms of AD. Studies have shown that Ginkgo biloba extract (EGb) is involved in intestinal metabolism to meet the goal of illness treatment. EGb is currently utilized extensively in the clinical prevention and treatment of cardiovascular and cerebrovascular diseases. However, the regulatory effect of EGb on intestinal flora and its metabolites in AD pathology remains largely speculative. In this study, the Morris water maze test showed a significant improvement of spatial memory in the AD mouse model (APP/PS1 mice) after EGb treatment. We next confirmed the positive effects of EGb on the gut flora and metabolites of APP/PS1 mice and further showed that EGb treatment reshaped the disturbed gut microbiome, in particular by reducing the Firmicutes/Bacteroides ratio and increasing the abundance of Bacteroidetes, Uroviricota, Streptophyta, and Spirochaetes. Meanwhile, a non-targeted metabolomics analysis showed that EGb treatment significantly reversed the dysfunction of the microbial metabolic phenotype by altering Limosilactobacillus and Parvibacte, with 300 differential metabolites modulated (131 up-regulated, 169 down-regulated). Our findings highlight the significant regulatory impact of EGb on intestinal microflora and microbial metabolism in AD mice models and provide a potential therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is more common in women, and many reports of sex differences have been reported in various aspects of RA. However, there has been a lack of specific research on women's gut flora. To assess the association between the gut flora and RA patients, this study combined the microbiome with metabolomics. Fecal samples from RA patients and healthy controls were collected for 16S rRNA sequencing. Nontargeted liquid chromatography–mass spectrometry was used to detect metabolites in fecal samples. We comprehensively used various analytical methods to reveal changes in intestinal flora and metabolites in female patients. The gut flora of RA patients was significantly different from that of healthy women. The abundance of Bacteroides, Megamonas and Oscillospira was higher in RA patients, while the abundance of Prevotella, Gemmiger and Roseburia was lower than that of healthy women. Gemmiger, Bilophila and Odoribacter represented large differences in microflora between RA and healthy women and could be used as potential microorganisms in the diagnosis. Fatty acid biosynthesis was significantly different between RA patients and healthy women in terms of metabolic pathways. There were different degrees of correlation between the gut flora and metabolites. Lys-Phe-Lys and heptadecasphin-4-enine can be used as potential markers for RA diagnosis. There was an extremely significant positive correlation between Megamonas, Dialister and rheumatoid factors, which was found for the first time. These findings indicated that alterations of these gut microbiome and metabolome may contribute to the diagnosis and treatment of RA patients. [ABSTRACT FROM AUTHOR]

The experiment was to study the effect of embrittlement feed on growth performance, muscle quality and intestinal flora of tilapia. A total of 120 fish were selected and divided into control group and experimental group, with three replicates per group. Tilapia in control group were fed commercial tilapia feed, and tilapia in the experimental group were fed self-made embrittlement feed. The experiment lasted for 90 d. The results showed that compared with control group, the WGR and SGR of tilapia in experimental groups were significantly decreased (P<0.05), and the FCR, VIS and HSI were increased. The crude protein and crude fat contents of muscle of tilapia in experimental group were significantly increased (P<0.05). The content of Lys, Asp, Glu, Gly and Ala in muscle of tilapia in experimental groups were significantly higher than those in control group (P<0.05). The content of TAA, EAA, UAA, EAAI, ΣUFA, ΣPUFA and ΣEFA were higher than those of control group. The muscle hardness, adhesion and mastication of tilapia in experimental group were significantly higher than those in control group (P<0.05). The proportion of Proteobacteria and Firmicutes in the intestinal tract of tilapia in test group was significantly lower than that in control group, but the bacterial community function was not significantly affected. The experiment indicates that embrittlement feed reduces the growth performance of tilapia, changes the structure of intestinal flora, and significantly improves the nutritional value and food quality of muscle. [ABSTRACT FROM AUTHOR]

Orally administered crocin rapidly and efficiently rescues depressive-like behaviors in depression models; however, crocin levels in the circulatory and central nervous systems are rather low. The underlying mechanism responsible for the inconsistency between pharmacokinetics and pharmacodynamics is unknown. To identify the active metabolites and clarify the underlying mechanisms, the pharmacokinetics and metabolic effects of the gut flora and hepatic and intestinal microsomes on crocin were examined, and the pharmacodynamics of crocin and its major metabolite, crocetin, were also evaluated in both normal and pseudo germ-free mice subjected to chronic social defeat stress. The results showed that oral administration of 300 mg/kg crocin significantly improved the depression-like behaviors of chronic social defeat stress mice, although the levels of crocin in the circulatory system were rather low (Cmax = 43.5 ± 8.6 μg/L; AUC = 151 ± 20.8 μg·h/L). However, the primary metabolite of crocetin was much more abundant in vivo (Cmax = 4662.5 ± 586.1 μg/L; AUC = 33,451.9 ± 3323.6 μg·h/L). Orally administered crocin was primarily metabolized into crocetin by the gut flora instead of hepatic or intestinal microsomal enzymes, and less than 10% of crocin was transformed into crocetin in the liver or intestinal microsomes. Inhibition of the gut flora dramatically reduced the production of and in vivo exposure to crocetin, and the rapid antidepressant effect of crocin disappeared. Moreover, crocetin showed rapid antidepressant effects similar to those of crocin, and the effects were independent of the gut flora. In conclusion, the metabolic transformation of crocin to crocetin primarily contributes to the rapid antidepressant effects of crocin and is dependent on the gut flora.

Enterococcus faecium B13, selected from fermentation chili, has been proven to promote animal growth by previous studies, but it belongs to opportunistic pathogens, so a comprehensive evaluation of its probiotic properties and safety is necessary. In this study, the probiotic properties and safety of B13 were evaluated at the genetic and phenotype levels in vitro and then confirmed in vivo. The genome of B13 contains one chromosome and two plasmids. The average nucleotide identity indicated that B13 was most closely related to the fermentation-plant-derived strain. The strain does not carry the major virulence genes of the clinical E. faecium strains but contains aac(6′)-Ii, ant (6)-Ia, msrC genes. The strain had a higher tolerance to acid at pH 3.0, 4.0, and 0.3% bile salt and a 32.83% free radical DPPH clearance rate. It can adhere to Caco-2 cells and reduce the adhesion of E. coli to Caco-2 cells. The safety assessment revealed that the strain showed no hemolysis and did not exhibit gelatinase, ornithine decarboxylase, lysine decarboxylase, or tryptophanase activity. It was sensitive to twelve antibiotics but was resistant to erythromycin, rifampicin, tetracycline, doxycycline, and minocycline. Experiments in vivo have shown that B13 can be located in the ileum and colon and has no adverse effects on experiment animals. After 28 days of feeding, B13 did not remarkable change the α-diversity of the gut flora or increase the virulence genes. Our study demonstrated that E. faecium B13 may be used as a probiotic candidate.

Hyaluronic acid (HA) is a new functional food additive which has the potential to ameliorate persistent inflammation, immunosuppression and catabolism syndrome (PICS), but the biological effects of HA with various molecular weights differ dramatically. To systematically investigate the efficacy of HA in altering PICS symptoms, medium-molecular-weight (MMW) HA was specifically selected to test its intervention effect on a PICS mouse model induced by CLP through oral administration, with high-molecular-weight (HMW) and low-molecular-weight (LMW) HA also participating in the experimental validation process. The results of pathological observations and gut flora showed that MMW HA rapidly alleviated lung lesions and intestinal structural changes in PICS mice in the short term. However, although long-term MMW HA administration significantly reduced the proportions of harmful bacteria in gut flora, inflammatory responses in the intestines and lungs of PICS mice were significantly higher in the MMW HA group than in the HMW HA and LMW HA groups. The use of HMW HA not only rapidly reduced the mortality rate of PICS mice but also improved their grip strength and the recovery of spleen and thymus indices. Furthermore, it consistently promoted the recovery of lung and intestinal tissues in PICS mice, and it also assisted in the sustained restoration of their gut microbiota. These effects were superior to those of LMW HA and MMW HA. The experimental results indicate that HMW weight HA has the greatest potential to be an adjunct in alleviating PICS as a food additive, while the safety of other HAs requires further attention.

Background In China, esophageal cancer is one of the most common cancers, and its incidence and mortality are more than twice the global average. However, most esophageal cancers in China are not detected until they are at moderate and advanced stages with poor prognosis, so early diagnosis and treatment are urgently needed. At present, the role of gut flora in the diagnosis and treatment of esophageal cancer has attracted much attention. Objective To explore the basic characteristics of gut flora in patients with esophageal squamous cell carcinoma. Methods From the Fourth Hospital of Hebei Medical University from April to August 2022, 35 patients with esophageal squamous cell carcinoma with no previous anti-cancer treatments were included as esophageal cancer group (EC group), and 35 healthy volunteers as control group. Stool samples of the two groups were collected to detect the gut flora using 16S rDNA sequence. Then an analysis was performed on the Alpha diversity, Beta diversity〔using the principal coordinate analysis (PCoA) 〕 and differential species of gut flora 〔using the linear discriminant analysis Effect Size (LEfSe) 〕 of two groups according to the species annotation of the test results. Results The Alpha diversity indices, such as Shannon index, Simpson index, Chao1 index, ACE index and Goods_coverage index demonstrated no significant differences between the two groups (P>0.05), while PCoA graph showed that the Beta diversity differed significantly between the two groups on the whole, and the community structures were different (t=10.837, P

Jintao Chen,1 Xinyi Wang,2 Zherong Xu1 1Department of Geriatrics, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 2Department of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Zherong Xu, Department of Geriatrics, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China, Email xzr1978@zju.edu.cnAbstract: Chronic pain and cognitive impairment are prevalent geriatric syndromes in the population of older adults, and they are the main cause of disability in people over sixty-five years of age. As the global population continues to age, chronic pain and cognitive impairment will affect an increasing number of older adults. While numerous studies in recent years have shown that chronic pain is associated with cognitive decline, the exact mechanisms linking the two remain unclear. In this review, we aim to present the available evidence on the connection between chronic pain and cognitive impairment and to discuss the potential mechanisms by which chronic pain affects cognitive function. In addition, we review potential therapeutic interventions targeting psychological factors, microglia activation, and altered gut flora that may improve and prevent cognitive decline in people with chronic pain.Keywords: chronic pain, cognitive impairment, microglia, psychosocial factors, gut flora

Scallop (Patinopecten yessoensis) male gonad hydrolysates/κ-carrageenan (SK) double cross-linking network hydrogels were constructed as curcumin (Cur) delivery vehicles with good gel mechanical property and homogeneous honeycomb microstructures. Compared with Cur + DSS group, weight loss and colon length in SK-Cur + DSS group increased about 1.04 and 1.06 folds, while the disease active index (DAI) scores decreased about 13 %. Moreover, SK-Cur showed superior effect on intestinal barrier improvement, oxidative stress modulation, and inflammatory expression regulation, reflected by 1.1 folds increment of epithelial tight junction proteins, 16 % and 27 % decline in MPO and iNOS levels, 20 % decline in NF-κB expression, 4 %, 7 %, 6 % decline in TNF-α, IL-1β, IL-6 expression in serum, and 9 %, 20 %, 7 % decline in TNF-α, IL-1β, IL-6 expression in colon tissue. Furthermore, SK-Cur enriched alpha diversity and restored taxonomic composition with increasing Bacteroides and Verrucomicrobia abundance accompanied by decreasing Firmicutes in DSS-induced UC mice, roughly to a normal gut flora state.

An exploration was conducted on the potential therapeutic properties of dandelion polysaccharide (DP) in addressing 3% dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in murine models. Subsequent assessments focused on DP's influence on inflammation, oxidative stress, and ferroptosis in IEC-6 cells damaged by H2O2. Results highlighted the efficacy of DP in mitigating weight loss, improving disease activity index scores, normalizing colon length, and alleviating histological abnormalities in the affected mice. DP repaired colonic mitochondrial damage by enhancing iron transport and inhibited iron death in colonic cells. Moreover, DP played a pivotal role in enhancing the antioxidant potential. This was evident from the increased expression levels of Nrf2, HO-1, NQO-1, and GSH, coupled with a decrease in MDA and 4-HNE markers in the UC-afflicted mice. Concurrently, DP manifested inhibitory effects on MPO activation and transcription levels of inflammatory mediators such as IL-1β, IL-6, TNF-α, and iNOS. An upsurge in the expression of occludin and ZO-1 was also observed. Restoration of intestinal tightness resulted in decreased serum LPS and LDH levels. Thereafter, administration of DP by gavage increased fecal flora diversity and relative abundance of probiotics in UC mice. Analysis of metabolites indicated that DP counteracted metabolic disturbances and augmented the levels of short-chain fatty acids in ulcerative colitis-affected mice. In vitro studies underscored the role of DP in triggering Nrf2 activation, which in turn exhibited anti-inflammatory, antioxidant, and anti-ferroptotic properties. Summarily, DP's capacity to activate Nrf2 contributes to the suppression of ferroptotic processes in intestinal epithelial cells of UC-affected mice, enhancing the intestinal barrier's integrity. Beyond that, DP possesses the ability to modulate the gut microbiome, rectify metabolic imbalances, rejuvenate short-chain fatty acid levels, and bolster the intestinal barrier as a therapeutic approach to UC. [ABSTRACT FROM AUTHOR]

It has been shown that Tibetan tea (TT) inhibits obesity and controls lipid metabolism. The fundamental processes by which TT prevents obesity are yet entirely unknown. Consequently, this research aimed to ascertain if TT may prevent obesity by modifying the gut flora. Our research demonstrated that TT prevented mice from gaining weight and accumulating fat due to the high‐fat diet (HFD), decreased levels of blood total cholesterol (TC), triglycerides (TG), and low‐density lipoprotein cholesterol (LDL‐C), and raised levels of high‐density lipoprotein cholesterol (HDL‐C). Adipogenesis‐related genes such as acetyl‐Coenzyme A carboxylase 1 (ACC1, LOC107476), fatty acid synthase (Fas, LOC14104), sterol regulatory element‐binding protein‐1c (SREBP‐1c, LOC20787), CCAAT/enhancer‐binding protein α (C/EBPα, LOC12606), stearoyl‐CoA desaturase 1 (SCD1, LOC20249), and peroxisome proliferator‐activated receptor γ (PPARγ, LOC19016) had their expression downregulated by lowering the Firmicutes/Bacteroidetes (F/B) ratio and controlling the number of certain gut bacteria. TT also alleviated HFD‐induced abnormalities of the gut microbiota. The Muribaculaceae, Lachnospiraceae NK4A136_group, Alistipes, and Odoribacter families were identified as the major beneficial gut microorganisms using Spearman's correlation analysis. Fecal microbiota transplantation (FMT) demonstrated that TT's anti‐obesity and gut microbiota‐modulating benefits might be transmitted to mice on an HFD, demonstrating that one of TT's targets for preventing obesity is the gut microbiota. TT also increased the amount of short‐chain fatty acids (SCFAs) in the feces, including acetic, propionic, and butyric acids. These results indicate the possible development of TT as a prebiotic to combat obesity and associated disorders. These results suggest that TT may act as a prebiotic against obesity and its associated diseases. [ABSTRACT FROM AUTHOR]

The gut microbiome is of tremendous relevance to human health and disease, so it is a hot topic of omics-driven biomedical research. However, a valid identification of gut microbiota-associated molecules in human blood or urine is difficult to achieve. We hypothesize that bowel evacuation is an easy-to-use approach to reveal such metabolites. A non-targeted and modifying group-assisted metabolomics approach (covering 40 types of modifications) was applied to investigate urine samples collected in two independent experiments at various time points before and after laxative use. Fasting over the same time period served as the control condition. As a result, depletion of the fecal microbiome significantly affected the levels of 331 metabolite ions in urine, including 100 modified metabolites. Dominating modifications were glucuronidations, carboxylations, sulfations, adenine conjugations, butyrylations, malonylations, and acetylations. A total of 32 compounds, including common, but also unexpected fecal microbiota-associated metabolites, were annotated. The applied strategy has potential to generate a microbiome-associated metabolite map (M3) of urine from healthy humans, and presumably also other body fluids. Comparative analyses of M3 vs. disease-related metabolite profiles, or therapy-dependent changes may open promising perspectives for human gut microbiome research and diagnostics beyond analyzing feces. [ABSTRACT FROM AUTHOR]

Ascophyllum nodosum, a brown algae abundantly found along the North Atlantic coast, is recognized for its high polysaccharide content. In this study, we investigated the anti-hyperlipidemic effect of fucoidans derived from A. nodosum, aiming to provide information for their potential application in anti-hyperlipidemic therapies and to explore comprehensive utilization of this Iceland brown seaweed. The crude fucoidan prepared from A. nodosum was separated using a diethylethanolamine column, resulting in two fucoidan fractions, AFC-1 and AFC-2. Both fractions were predominantly composed of fucose and xylose. AFC-1 exhibited a higher sulfate content of 27.8% compared to AFC-2 with 17.0%. AFC-2 was primarily sulfated at the hydroxy group of C2, whereas AFC-1 was sulfated at both the hydroxy groups of C2 and C4. To evaluate the anti-hyperlipidemic effect, a hyperlipidemia mouse model was established by feeding mice a high-fat diet. The effects of AFC-1, AFC-2, and the crude extract were investigated, with the drug atorvastatin used as a positive comparison. Among the different fucoidan fractions and doses, the high dose of AFC-2 administration demonstrated the most significant anti-hyperlipidemic effect across various aspects, including physiological parameters, blood glucose levels, lipid profile, histological analysis, and the activities of oxidative stress-related enzymes and lipoprotein-metabolism-related enzymes (p < 0.05 for the final body weight and p < 0.01 for the rest indicators, compared with the model group), and its effect is comparable to the atorvastatin administration. Furthermore, fucoidan administration resulted in a lower degree of loss in gut flora diversity compared to atorvastatin administration. These findings highlight the significant biomedical potential of fucoidans derived from A. nodosum as a promising therapeutic solution for hypolipidemia. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease is a heterogeneous intestinal inflammatory disorder, including ulcerative colitis (UC) and Crohn's disease (CD). Existing studies have shown that the pathogenesis of IBD is closely related to the host's genetic susceptibility, intestinal flora disturbance and mucosal immune abnormalities, etc. It is generally believed that there are complicated interactions between host immunity and intestinal microflora/microRNAs during the occurrence and progression of IBD. Intestinal flora is mainly composed of bacteria, fungi, viruses and helminths. These commensals are highly implicated in the maintenance of intestinal microenvironment homeostasis alone or in combination. MiRNA is an endogenous non-coding small RNA with a length of 20 to 22 nucleotides, which can perform a variety of biological functions by silencing or activating target genes through complementary pairing bonds. A large quantity of miRNAs are involved in intestinal inflammation, mucosal barrier integrity, autophagy, vesicle transportation and other small RNA alterations in IBD circumstance. In this review, the immunomodulatory roles of gut flora and microRNAs are updated in the occurrence and progression of IBD. Meanwhile, the gut flora and microRNA targeted therapeutic strategies as well as other immunomodulatory approaches including TNF-α monoclonal antibodies are also emphasized in the treatment of IBD. [ABSTRACT FROM AUTHOR]

Background and aim: Qingfei Jiedu Granules (QFJD) are a new Traditional Chinese Medicine (TCM) which has been clinically used against coronavirus pneumonia in China. In this study, the therapeutic effect and the underlying mechanisms of QFJD against influenza were investigated. Experimental procedure: Pneumonia mice were induced by influenza A virus. Survival rate, weight loss, lung index and lung pathology were measured to evaluate the therapeutic effect of QFJD. The expression of inflammatory factors and lymphocytes was used to assess anti-inflammatory and immunomodulatory effect of QFJD. Gut microbiome analysis was performed to decipher the potential effect of QFJD on intestinal microbiota. Metabolomics approach was conducted to explore the overall metabolic regulation of QFJD. Result and conclusion: QFJD shows a significant therapeutic effect on the treatment of influenza and the expression of many pro-inflammatory cytokines were obviously inhibited. QFJD also markedly modulates the level of T and B lymphocytes. The high-dose QFJD has shown similar therapeutic efficiency compared to positive drugs. QFJD profoundly enriched Verrucomicrobia and maintained the balance between Bacteroides and Firmicutes. QFJD associated with 12 signaling pathways in metabolomics study, 9 of which were the same as the model group and were closely related to citrate cycle and amino acid metabolism.To sum up, QFJD is a novel and promising drug against influenza. It can regulate inflammation, immunity, metabolism, and gut microbiota to fight influenza. Verrucomicrobia shows great potential to improve influenza infection and may be an important target.

Diet and nutrition have a tremendous influence on health and disease. Dietary constituents can affect health and have been known to supplement with essential nutrients, minerals, and calories for physiological homeostasis. However, diet can also affect gene expression through epigenetic reprogramming or by altering the level of micronutrients. While a nutrigenomics study has delineated this causal link, a recent study published in EMBO Molecular Medicine by Grant et al. went a step further to establish that maternal intake of dietary fibers can alter the fetal gut microbiome, influencing the diversity of the intestinal bacterial flora, thereby affecting the gut-brain axis. Although the relationship between diet and fertility in males and females has been reported, the effect on postnatal life is not well documented. In this study by Grant et al. at the (Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg), the authors reported that selected feeding of fiber-free diets to pregnant mice alters the gut microbiome composition of their neonate pups depriving them of protective and beneficial commensal, Akkermansia muciniphila, a mucin-foraging bacterium. Further, these animals exhibited heightened immune activity by enriching defense response pathways and IL-22 expression. Therefore, the protective role of A. muciniphila is associated with its protection against chronic inflammation through TLR4 signaling. The author’s study has far-reaching conclusions on improving human health outcomes by the rational choice of food, drugs, and lifestyle to prevent gut dysbiosis and colonization of the right microbiome.

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is multifactorial and composite, with the disorder of lipid metabolism‐induced lipotoxicity being one of the main risk factors. Atorvastatin (AT), the most widely prescribed lipid‐lowering drug, has pleiotropic actions benefiting NAFLD treatment. However, low absorption rate in the gut and potential disruption of AT on gut flora hindered its further applications. Notably, gut dysbiosis is involved in and is thus a promising management strategy for NAFLD. In this study, we constructed a prebiotic‐based AT nanoamorphous (PANA) to improve the efficacy of AT against NAFLD by retrieving liver and gut health. After oral administration, PANA showed superior drug accumulation in the liver tissue compared with pure AT. Moreover, PANA intervention effectively restored gut healthiness, indicated by reconstructed gut flora, and improved intestinal immunity, barrier integrity, and inflammation. Consequently, compared with AT, PANA treatment caused profound inhibition of weight gain and fat deposition, decreased plasma lipid levels, and alleviated hepatic steatosis and liver inflammation. The transcriptome analysis in the gut and liver tissues identified improved immunity and inflammation as potential mechanisms. This study suggests a promising strategy to treat NAFLD, assisted with nanotechnology in synergy with functional biomaterials.

In this study, we evaluate the effects of Weizmannia coagulans SANK70258 intake on skin condition and defecation, both alone and in combination with galacto-oligosaccharides, by conducting a randomized, double-blind, parallel-group, placebo-controlled, eight-week study of 45 healthy individuals. The primary endpoints were measurement of the stratum corneum moisture content, transepidermal water loss, and skin texture; the secondary endpoints were skin assessment, a defecation survey, and measurement of fecal organic acid and p-cresol contents. The participants were divided into a W. coagulans SANK70258 alone (lac + dex) group, a W. coagulans SANK70258 plus galacto-oligosaccharides (lac + gal) group, and a placebo (dex) group. The lac + gal group showed a decrease in skin roughness and fecal p-cresol content. Scaliness was improved in lac + dex and lac + gal groups. Thus, synbiotics combining W. coagulans SANK70258 and galacto-oligosaccharides can improve scaliness and skin roughness and reduce fecal p-cresol content.