Microbiota Metabolites Research Articles

A role of gut microbiota metabolites in HLA-E and NKG2 blockage immunotherapy against tumors: new insights for clinical application.

One of major breakthroughs in immunotherapy against tumor is from blocking immune checkpoint molecules on tumor and reactive T cells. The development of CTLA-4 and PD-1 blockage antibodies has triggered to search for additional effective therapeutic strategies. This causes recent findings that blocking the interaction of checkpoint molecule NKG2A in NK and CD8 T cells with HLA-E in tumors is effective in defensing tumors. Interestingly, gut microbiota also affects this immune checkpoint immunotherapy against tumor. Gut microbiota such as bacteria can contribute to the regulation of host immune response and homeostasis. They not only promote the differentiation and function of immunosuppressive cells but also the inflammatory cells through the metabolites such as tryptophan (Trp) and bile acid (BA) metabolites as well as short chain fatty acids (SCFAs). These gut microbiota metabolites (GMMs) educated immune cells can affect the differentiation and function of effective CD8 and NK cells. Notably, these metabolites also directly affect the activity of CD8 and NK cells. Furthermore, the expression of CD94/NKG2A in the immune cells and/or their ligand HLA-E in the tumor cells is also regulated by gut microbiota associated immune factors. These findings offer new insights for the clinical application of gut microbiota in precise and/or personalized treatments of tumors. In this review, we will discuss the impacts of GMMs and GMM educated immune cells on the activity of effective CD8 and NK cells and the expression of CD94/NKG2A in immune cells and/or their ligand HLA-E in tumor cells.

Dietary pattern and gut microbiota in type 2 Diabetes Mellitus: A literature review

Nutrition has been identified as the primary modifiable factor The type of food, the macronutrient and micronutrient composition of the diet has distinct effects on gut microbiota and related metabolites. These impacts significantly influence mechanisms that regulate hyperglycemia and insulin resistance influencing gut microbiota remodeling and the development of T2DM. This study aimed to gather information on changes in gut microbiota composition (Lactobacillus and Bifidobacterium) and describe the beneficial or detrimental effects, impacts, and outcomes of macronutrients (carbohydrate, protein, and fat) and fiber on gut microbiota composition in T2DM. A total of 9 English articles were obtained from the results of the literature review. Lactobacillus and Bifidobacterium can positively reduce the blood glucose levels. Changes in the gut microbiota and its metabolites, which are influenced by carbohydrate, protein, lipid, and fiber intake, can worsen or decrease biochemical parameters and improve complications of T2DM. The conclusion of this literature review was gut microbiota can be crucial in the future treatment of diabetes mellitus, especially in combination with other therapeutic options.

Zearalenone-induced hepatointestinal toxicity in laying hens: unveiling the role of gut microbiota and fecal metabolites

Zearalenone (ZEN), a mycotoxin produced by Fusarium species, is known for its reproductive toxicity as an estrogen analogue. However, there are limited knowledge about its hepatointestinal toxicity, as well as the role that gut microbiota and metabolites play in this process. In this study, a total of 24 thirty-week-old hens were fed to investigate the hepatointestinal toxicity subjected to long-term ZEN consumption at 2.0 mg/kg for 90 d. And we employed uncultured 16S rRNA sequencing for gut microbiota and untargeted metabolomics for fecal metabolites assessment. Notably, ZEN induced significant hepatic damage, as evidenced by hepatocyte necrosis, inflammatory cell infiltrate, increased liver lipopolysaccharide (LPS) and blood aspartate aminotransferase (AST) levels (P < 0.05). The decreased villus height, disruption of simple columnar epithelial cells, and exposure of the mucosal intrinsic layer were observed in the intestine. The gut microbial community composition and metabolites differed between ZEN group and control group. ZEN group exhibited higher gut microbial diversity (P < 0.05), lower Firmicutes/Bacteroidetes ratio and Lactobacillus abundance, and higher abundance in the genus such as Bacteroidetes, Parabacteroidetes and Desulfovibrio. Metabolomic analysis showed that ZEN treatment altered biosynthesis of siderophore group nonribosomal peptides and phenylpropanoids, metabolism of amino acid, digestion and absorption of vitamin and ABC transporters. Differential metabolites suggested that ZEN increase the risk of estrogen disorder, nucleic acid degradation, intestinal oxidative stress and inflammation. Neural network analysis showed that Ruminococcus was positively correlated with glyceric acid, and Prevotella was positively correlated with phenylacetylglycine. Both metabolites were positively correlated with blood AST level (P < 0.05), suggesting that intestinal microbe Ruminococcus and Prevotella might exacerbate liver damage by producing these harmful metabolites. Overall, we conclude that ZEN has damaged hepatointestinal system and the altered gut microbiota with resultant metabolite changes contribute to the adverse hepatointestinal effects of ZEN on laying hens. This study underscores the need for monitoring and mitigating ZEN exposure in poultry diets, highlighting its broader implications for animal health and food safety.

Hydrogen-rich water alleviates asthma airway inflammation by modulating tryptophan metabolism and activating aryl hydrocarbon receptor via gut microbiota regulation

Hydrogen-rich water (HRW) is a beverage containing a high concentration of hydrogen that has been researched for its antioxidant, anti-apoptotic, and anti-inflammatory properties in asthma. This study investigates the potential therapeutic impact of HRW on the gut-lung axis. Using 16S rRNA and serum metabolomics, we examined changes in gut microbiota and serum metabolites in asthmatic mice after HRW intervention, followed by validation experiments. The findings revealed that HRW influenced gut microbiota by increasing Ligilactobacillus and Bifidobacterium abundance and enhancing the presence of indole-3-acetic acid (IAA), a microbially derived serum metabolite. Both in vivo and in vitro experiments showed that HRW's protective effects against airway inflammation in asthmatic mice may be linked to the gut microbiota, with IAA potentially playing a role in reducing asthmatic airway inflammation through the aryl hydrocarbon receptors (AhR) signaling pathway. In summary, HRW can modify gut microbiota, increase Bifidobacterium abundance, elevate microbial-derived IAA levels, and activate AhR, which could potentially alleviate inflammation in asthma.

Macrogenomic and Metabolomic Analyses Reveal Mechanisms of Gut Microbiota and Microbial Metabolites in Diarrhea of Weaned Piglets.

Recent studies have shown a correlation between piglet diarrhea and the gut microbiota. However, the precise mechanism by which intestinal microorganisms and their metabolites influence diarrhea in weaned piglets remains unclear. This study explored differences in the gut microbiota and associated metabolites between healthy and diarrheic-weaned piglets using macrogenomic and metabolomic analyses. The histomorphological results showed that diarrheic piglets had shorter jejunal and ileal villi, some of which were shed, compared to healthy piglets. Substantial differences in gut microbial diversity and metabolites were also observed, with Bacteroidaceae bacterium and Caudoviricetes being the main differential organisms that were strongly correlated with host status. Microbial functions, mainly the metabolism of carbohydrates, glycans, lipids, and amino acids, as well as related enzyme activities, were substantially different. The major differential metabolites were carnosine, pantothenic acid (vitamin B5), pyridoxal, methylimidazoleacetic acid, indole-3-acetaldehyde, and 5-hydroxyindoleacetic acid. These metabolites were enriched in beta-alanine, histidine, tryptophan, and vitamin B6 metabolism, and in the pantothenate and CoA biosynthesis pathways. Combined macrogenomic and metabolomic analyses revealed that carnosine, vitamin B5, and pyridoxal were negatively correlated with Caudoviricetes; methylimidazoleacetic acid, indole-3-acetaldehyde, and 5-hydroxyindoleacetic acid were positively correlated with Caudoviricetes. Whereas carnosine and vitamin B5 were positively correlated with Bacteroidaceae bacterium, 5-hydroxyindoleacetic acid was negatively correlated. The decreased abundance of Bacteroidaceae bacterium and the increased abundance of Caudoviricetes and related metabolites likely contribute to post-weaning diarrhea in piglets. Therefore, the abundance of Bacteroidaceae bacterium and Caudoviricetes can likely serve as potential markers for identifying and preventing diarrhea in post-weaning piglets.

Erythrocyte Very Long-Chain Saturated Fatty Acids, Gut Microbiota-Bile Acid Axis, and Incident Coronary Artery Disease in Adults: A Prospective Cohort Study

BackgroundPrior research has highlighted inverse associations between concentrations of circulating very long-chain saturated fatty acids (VLCSFAs) and coronary artery disease (CAD). However, the intricate links involving VLCSFAs, gut microbiota, and bile acids remain underexplored. ObjectivesThis study examined the association of erythrocyte VLCSFAs with CHD incidence, focusing on the mediating role of gut microbiota and fecal bile acids. MethodsThis 10-y prospective study included 2383 participants without CHD at baseline. Erythrocyte VLCSFAs [arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)] were measured using gas chromatography at baseline, and 274 CHD incidents were documented in triennial follow-ups. Gut microbiota in 1744 participants and fecal bile acid metabolites in 945 participants were analyzed using 16S ribosomal ribonucleic acid sequencing and ultra-performance liquid chromatography-tandem mass spectrometry at middle-term. ResultsThe multivariable-adjusted hazard ratios (95% confidence interval) for CHD incidence in highest compared with lowest quartiles were 0.87 (0.61, 1.25) for C20:0, 0.63 (0.42, 0.96) for C22:0, 0.59 (0.41, 0.85) for C24:0, and 0.57 (0.39, 0.83) for total VLCSFAs. Participants with higher total VLCSFA concentrations exhibited increased abundances of Holdemanella, Coriobacteriales Incertae Sedis spp., Ruminococcaceae UCG-005 and UCG-010, and Lachnospiraceae ND3007 group. These 5 genera generated overlapping differential microbial scores (ODMSs) that accounted for 11.52% of the total VLCSFAs-CHD association (Pmediation = 0.018). Bile acids tauro_α_ and tauro_β_muricholic acid were inversely associated with ODMS and positively associated with incident CHD. Opposite associations were found for glycolithocholic acid and glycodeoxycholic acid. Mediation analyses indicated that glycolithocholic acid, glycodeoxycholic acid, and tauro_α_ and tauro_β_muricholic acid explained 56.40%, 35.19%, and 26.17% of the ODMS-CHD association, respectively (Pmediation = 0.002, 0.008, and 0.020). ConclusionsElevated erythrocyte VLCSFAs are inversely associated with CHD risk in the Chinese population, with gut microbiota and fecal bile acid profiles potentially mediating this association. The identified microbiota and bile acid metabolites may serve as potential intervention targets in future studies.This trial was registered at www.clinicaltrials.gov as NCT03179657.

Lingguizhugan decoction ameliorates cognitive impairment in AD-like mice by influencing the microbiome–gut–brain axis mediated by SCFAs

BackgroundLingguizhugan (LGZG) decoction, an ancient Chinese herbal remedy originating from the Eastern Han Dynasty, consists of Poria cocos, Cinnamomi ramulus, Atractylodes macrocephala, and Glycyrrhiza, as described in the Golden Chamber Synopsis. It has a history spanning over 1600 years, in which it has been primarily used for the treatment of inflammation, injuries, and fluid retention; however, the potential of LGZG decoction to ameliorate Alzheimer's disease (AD) progression by modulating the gut–brain axis through attenuation of gut microbiota and their metabolites remains unknown. PurposeTo examine the in vivo anti-AD effects and mechanism of LGZG decoction in alleviating AD cognitive impairment. Study designTwo-part experiments in vivo were designed, one for behavior tests, intestinal and brain histopathology, intestinal microbiome and quantitative determination, and another one for metabolite supplementation study. MethodsAlCl3/D-gal was used to establish an AD-like mouse model. Behavioral tests, such as the Morris water maze test, were used to assess the effect of LGZG decoction on cognitive dysfunction. The concentration of proinflammatory mediators was measured by ELISA. The protein content was detected by western blot analysis and immunohistochemistry. The content of short-chain fatty acids was measured by LC-MS/MS. Evaluation of 16S rRNA gene sequencing for species and strain-level gut microbiome analysis was performed. ResultsLGZG decoction mitigated cognitive impairment in an AD-like mouse model, and decreased the deposition of amyloid-β and the production of proinflammatory cytokines in the brain. LGZG decoction remodeled the intestinal microecology, enhanced the integrity of the intestinal and brain tissue barriers, and modulated Aβ transportation through gut microbiota metabolite SCFAs. The neuroprotective effect of SCFAs on the AD-like model mice may be manifested through the inhibition of pP38 of the MAPK signaling pathway. ConclusionOur results suggest that LGZG decoction reshapes the gut microbiota. SCFAs derived from the gut microbiota ameliorate the cognitive decline induced by AlCl3/D-gal through the gut–brain axis and reduce brain Aβ aggregation. We propose LGZG decoction as a potential therapeutic option for AD.

The metabolic and endocrine impact of diet-derived gut microbiota metabolites on ageing and longevity

Gut dysbiosis has been recently recognized as a hallmark of ageing. At this stage of life, gut microbiota becomes depleted from bacteria involved in the production of short-chain fatty acids (SCFA), indole and its derivative indole-3-propionic acid (IPA), metabolites shown to improve host glycemic control as well as insulin sensitivity and secretion. Moreover, gut microbiota becomes enriched in pathobiont bacteria involved in the production of imidazole propionate, phenols and trimethylamine, metabolites that promote host insulin resistance and atherosclerosis. The magnitude of these changes is much more pronounced in unhealthy than in healthy ageing. On the other hand, a distinct gut microbiota signature is displayed during longevity, the most prominent being an enrichment in both SCFA and IPA bacterial producers. This short Review discusses, in an innovative and integrative way, cutting-edge research on the composition of gut microorganisms and profile of metabolites secreted by them, that are associated with a healthy and unhealthy ageing pattern and with longevity. A detailed description of the positive or detrimental metabolic effects, in the ageing host, of diet-derived gut microbial metabolites is provided. Finally, microbiota-targeted interventions that counteract gut dysbiosis associated with ageing, are briefly outlined.

Possible immune mechanisms of gut microbiota and its metabolites in the occurrence and development of immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by increased platelet destruction and impaired production, leading to an elevated bleeding tendency. Recent studies have demonstrated an important link between the gut microbiota and the onset and progression of several immune diseases in humans, emphasizing that gut microbiota-derived metabolites play a non-negligible role in autoimmune diseases. The gut microbiota and its metabolites, such as short-chain fatty acids, oxidized trimethylamine, tryptophan metabolites, secondary bile acids and lipopolysaccharides, can alter intestinal barrier permeability by modulating immune cell differentiation and cytokine secretion, which in turn affects the systemic immune function of the host. It is therefore reasonable to hypothesize that ecological dysregulation of the gut microbiota may be an entirely new factor in the triggering of ITP. This article reviews the potential immune-related mechanisms of the gut microbiota and representative metabolites in ITP, as well as the important influence of leaky gut on the development of ITP, with a view to enriching the theoretical system of ITP-related gut microecology and providing new ideas for the study of ITP.

Characteristics of stachyose-induced effects on gut microbiota and microbial metabolites in vitro associated with obesity in children.

Childhood obesity presents a serious health concern associated with gut microbiota alterations. Dietary interventions targeting the gut microbiota have emerged as promising strategies for managing obesity in children. This study aimed to elucidate the impact of stachyose (STS) supplementation on the gut microbiota composition and metabolic processes in obese children. Fecal samples were collected from 40 obese children (20 boys and 20 girls) aged between 6 and 15 and in vitro fermentation was conducted with or without the addition of STS, respectively, followed by 16S rRNA amplicon sequencing and analysis of short-chain fatty acids (SCFAs) and gases. Notably, our results revealed that STS supplementation led to significant alterations in gut microbiota composition, including an increase in the abundance of beneficial bacteria such as Bifidobacterium and Faecalibacterium, and a decrease in harmful bacteria including Escherichia-Shigella, Parabacteroides, Eggerthella, and Flavonifractor. Moreover, STS supplementation resulted in changes in SCFAs production, with significant increases in acetate levels and reductions in propionate and propionate, while simultaneously reducing the generation of gases such as H2S, H2, and NH3. The Area Under the Curve (AUC)-Random Forest algorithm and PICRUSt 2 were employed to identify valuable biomarkers and predict associations between the gut microbiota, metabolites, and metabolic pathways. The results not only contribute to the elucidation of STS's modulatory effects on gut microbiota but also underscore its potential in shaping metabolic activities within the gastrointestinal environment. Furthermore, our study underscores the significance of personalized nutrition interventions, particularly utilizing STS supplementation, in the management of childhood obesity through targeted modulation of gut microbial ecology and metabolic function.

Imperata cylindrica polysaccharide ameliorates intestinal dysbiosis and damage in hyperuricemic nephropathy

In this study, a combination of adenine and potassium oxonate was utilized to establish a hyperuricemic nephropathy (HN) mouse model, aiming to elucidate the effect through which Imperata Cylindrica polysaccharide (ICPC-a) ameliorates HN. In HN mice, an elevation in the abundance of Erysipelatoclostridium, Enterococcus, Prevotella, and Escherichia-Shigella was observed, whereas Lactobacillus and Bifidobacterium declined. Additionally, the systemic reductions in the levels of acetate, propionate, and butyrate, along with a significant increase in indole content, were noted. HN mice demonstrated intestinal barrier impairment, as evidenced by diminished mRNA expression of ZO-1, Occludin, and Claudin-1 and increased Mmp-9 levels. The pro-inflammatory factors IL-6, IL-17, TNF-α, IFN-γ, and COX-2 were overexpressed. Subsequent gavage intervention with ICPC-a markedly mitigated the inflammatory response and ameliorated colon tissue damage. ICPC-a effectively regulated the abundance of gut microbiota and their metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and indole, promoting the correction of metabolic and gut microbiota imbalances in HN mice. These findings underscored the capacity of ICPC-a as a prebiotic to modulate gut microbiota and microbial metabolites, thereby exerting a multi-pathway and multi-targeted therapeutic effect on HN.

Efficacy of probiotics/synbiotics supplementation in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.

Chronic kidney disease (CKD) is a serious and steadily growing health problem worldwide. Probiotic and synbiotic supplementation are expected to improve kidney function in CKD patients by altering imbalanced intestinal flora, regulating microbiota metabolites, modulating the brain-gut axis, and reducing inflammation. Our aim is to report the latest and largest pooled analyses and evidence updates to explore whether probiotic and synbiotic have beneficial effects on renal function and general conditions in patients with CKD. We conducted a systematic literature search using PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from inception until 1 December 2023. Eligible literatures were screened according to inclusion and exclusion criteria, data were extracted, and a systematic review and meta-analysis was performed. Measurements included renal function-related markers, inflammatory markers, uremic toxins, lipid metabolism-related markers and electrolytes levels. Twenty-one studies were included. The results showed that probiotic/synbiotic significantly reduced blood urea nitrogen (BUN) (standardized mean difference (SMD), -0.23, 95% confidence interval (CI) -0.41, -0.04; p = 0.02, I2 = 10%) and lowered c-reactive protein level (CRP) (SMD: -0.34; 95% CI: -0.62, -0.07; p = 0.01, I2 = 37%) in CKD patients, compared with the control group. In summary, probiotic/synbiotic supplementation seems to be effective in improving renal function indices and inflammation indices in CKD patients. Subgroup analyses suggested that longer-term supplementation is more favorable for CKD patients, but there is a high degree of heterogeneity in the results of partial subgroup analyses. The efficacy of probiotic/synbiotic in treating CKD needs to be supported by more evidence from large-scale clinical studies. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024526836, Unique identifier: CRD42024526836.

Advances in Research on the Impact of Diet on Human Gut Microbiota Composition and Metabolites

As research into gut microbiota deepens, the impact of diet on the composition of human gut microbiota and their metabolites has gradually become a focal point. This paper reviews recent advancements in understanding how diet influences gut microbiota composition and their metabolic products. Firstly, it introduces the basic concepts of gut microbiota and their role in maintaining health. Next, it explores the effects of different types of diets (such as high-fiber, high-fat, high-protein, and refined sugar diets) on the composition of gut microbiota and analyzes their impact on microbiota diversity. Then, it discusses the influence of diet on gut microbiota metabolites, including short-chain fatty acids, amino acid metabolites, and gases. Further, it examines the practical applications of dietary interventions on health, especially their potential impact on chronic diseases. Finally, the paper summarizes the limitations of current research and suggests future research directions and challenges. Overall, the influence of diet on gut microbiota and their metabolites holds profound health significance and provides important evidence for formulating scientific dietary recommendations.

Synthesis of N-(3-Acyloxyacyl)glycines, Small Molecules with Potential Role in Gut Microbiome-Endocannabinoidome Communication.

The synthesis of some N-(3-acyloxyacyl)glycines, an interesting class of bioactive gut microbiota metabolites, is described. This procedure involves seven reaction steps using the commercially available Meldrum's acid to obtain highly pure products, in normal or deuterated form. The key point of the synthetic strategy was the use of commendamide t-butyl ester as a synthetic intermediate, a choice that allowed the removal of the protecting group at the end of the synthetic procedure without degrading of the other ester bond present in the molecule. The developed synthetic sequence is particularly simple, uses readily available reagents and involves a limited number of purifications by chromatographic column, with a reduction in the volume of solvent and energy used.

Potential role of short-chain fatty acids in the pathogenesis and management of acute lymphocytic leukemia.

Acute lymphocytic leukemia (ALL) is an aggressive hematological malignancy of highly proliferative lymphoblasts. ALL is the most common cancer in children, and is typically treated with combination chemotherapy. The 5-year survival of ALL improved significantly in recent decades with this treatment approach. However, certain age groups (below 2 and over 10 years of age) have much worse prognosis, and over 50% of patients with ALL experience long-term side effects proportional to the dosage of anticancer drugs. Therefore, different treatment strategies are required to improve survival in ALL and to reduce side effects of chemotherapy. Since epigenetic modifications are dominantly reversible, "epidrugs" (drugs targeting epigenetic markers) are considered for feasibility in the treatment of ALL as epigenetic modifications, and acetylation of histones was demonstrated to play a critical role in the pathogenesis of ALL. Histone deacetylases (HDACs) have been shown to be differentially expressed in several hematological malignancies, including ALL. HDAC inhibitors (HDACis) have been shown to express selective toxicity for ALL cells, but they showed limited efficacy and higher than expected toxicity in mouse models or clinical trials in ALL. The aim of this review is to examine the role of the microbiota and microbial metabolites in the mechanisms of HDAC functions, and explore the utilization of the microbiota and microbial metabolites in improving the efficacy of HDACi in ALL. HDAC regulators and natural HDACi are depleted in ALL due to microbiota change leading to a decrease in butyrate and propionate, and HDACi treatment is not effective in ALL due to their short half-life. We propose that HDACi released by the microbiota may be necessary in HDAC regulation and this process is impaired in ALL. Furthermore, the review will also consider the role of restoration of the microbiota or supplementation of natural HDACi in potentially restoring HDAC and HDACi functions.

Long-term cadmium stress influenced the immune response of Pardosa pseudoannulata by modulating its gut microbiota and hemolymph metabolome

Cadmium (Cd) is a common environmental heavy metal pollutant known for its toxic effects on various plants and animals. Cd contamination also poses a threat to Pardosa pseudoannulata, a predator in rice paddies. Results indicate that Cd pollution significantly reduced the levels of Metallothionein, phenoloxidase, and Ca2+. Furthermore, through metabolomics and 16S rDNA sequencing, alterations in the gut microbiota and immune-related metabolites of P. pseudoannulata were identified. The abundance of harmful bacteria such as Staphylococcus increased significantly, while levels of l-Tyrosine, glutathione disulfide, l-Dopa, among others, decreased markedly. Pearson correlation analysis revealed significant associations between various gut microbes and immune-related metabolites, suggesting that Cd may alter the immune system of P. pseudoannulata by modulating its gut microbiota.

Gut microbiota-derived metabolite trimethylamine N-oxide aggravates cognitive dysfunction induced by femoral fracture operation in mice.

An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N-oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO-induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ-free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO-related POCD and improving the quality of life for elderly patients.

Fuzi lizhong pills alter microbial community compositions and metabolite profiles in ulcerative colitis rat with spleen-kidney yang deficiency syndrome

Ethnopharmacological relevanceUlcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown. Aim of the studyThe goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC. Materials and methodsTo investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms. ResultsFLZP contains 109 components, including liquiritin (584.8176 μg/g), benzoylaconine (16.3087 μg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 μg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle. ConclusionsFLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management.

Co-culture of Tetragenococcus halophilus and Zygosaccharomyces rouxii to improve microbiota and metabolites in secondary fortified fermented soy sauce

This study employed metagenomics and metabolomics to evaluate the impact of Tetragenococcus halophilus and Zygosaccharomyces rouxii on microbiota composition and metabolite profiles in secondary fortified fermented soy sauce. The Co-culturing of T. halophilus T10 and Z. rouxii QH-1(T1Z) enriched microbial diversity and promoted the proliferation of functional species, thereby enhancing biomarker species. Annotations matched from EggNOG, KEGG, and CAZy databases underscored the significance of carbohydrate and amino acid metabolism in moromi. Sample T1Z enhanced the metabolism by increasing the abundance and catalytic efficiency of the relevant enzymes, resulting in increases of 3.94%, 2.69%, and 11.14%, respectively, with total nitrogen, amino acid nitrogen, and free amino acids. It introduced 11 volatile compounds and increased the alcohol content by 13.65%, and the aldehyde content by 49.28%, while also suppressing the accumulation of ammonium nitrogen and biogenic amines. Metabolic pathway analysis identified Staphylococcus gallinarum, Mammaliicoccus sciuri, and certain Bacillus species, especially B. parathracis, B. velezensis, and B. subtilis, as principal contributors to carbohydrate and amino acid metabolism. These findings offer insight into microbial strain selection for industrial fermentation and provide a foundation for optimizing the process through co-culture bioaugmentation to enhance and underscore the potential of modern microbial techniques in traditional practices.

Metabolites mediate the causal associations between gut microbiota and NAFLD: a Mendelian randomization study

BackgroundAlthough gut microbiota and serum metabolite composition have been observed to be altered in patients with non-alcoholic fatty liver disease (NAFLD), previous observational studies have demonstrated inconsistent results. As this may be influenced by factors such as confounders and reverse causality, we used Mendelian randomization to clarify the causal effect of gut microbiota and blood metabolites on NAFLD.MethodsIn this research, we performed a two-step Mendelian randomization analysis by utilizing genome-wide association study (GWAS) data obtained from MiBioGen and UK Biobank. To mitigate potential errors, we employed False Discovery Rate (FDR) correction and linkage unbalanced regression (LDSC) analysis. Sensitivity analyses including cML-MA and bidirectional Mendelian randomization were performed to ensure the robustness of the results.ResultsIn this study, a total of nine gut microbiota and seven metabolites were found to be significantly associated with NAFLD. MR analysis of the above findings revealed a causal relationship between Ruminococcus2 and cysteine-glutathione disulfide (OR = 1.17, 95%CI = 1.006–1.369, P = 0.041), as well as 3-indoleglyoxylic acid (OR = 1.18, 95%CI = 1.011–1.370, P = 0.036). For each incremental standard deviation in Ruminococcus2 abundance, there was a corresponding 26% reduction in NAFLD risk (OR = 0.74, 95%CI = 0.61–0.89, P = 0.0012), accompanied by a 17% increase in cysteine-glutathione disulfide levels (OR = 1.17, 95%CI = 1.01–1.37, P = 0.041) and an 18% increase in 3-indoleglyoxylic acid levels (OR = 1.18, 95%CI = 0.81-1.00, P = 0.036). The proportion mediated by cysteine-glutathione disulfide is 11.2%, while the proportion mediated by 3-indoleglyoxylic acid is 7.5%.ConclusionOur study suggests that increased abundance of specific gut microbiota may reduce the risk of developing NAFLD, and this relationship could potentially be mediated through blood metabolites.