Microbiota Metabolites Research Articles

Gut microbiota participates and remodels host metabolism: From treating patients to treating their gut flora

In this editorial, we comment on Liu et al’ s article published in the recent issue of the World Journal of Gastroenterology . Biochemically and pathologically, Liu et al proved that the urate-lowering activity of leech total protein (LTP) was mainly attributed to the rectification of gut microbiota. Specifically, we noticed the change in Bacteroides and Akkermansia after LTP administration. Both bacteria have been reported to alleviate metabolic dysfunction-associated steatohepatitis and other chronic metabolic diseases. LTP was administrated through intragastric manners. Most possibly, LTP would be digested by the gut microbiota further. The anti-hyperuricemia effects should, to the most possible extent, be exerted by the peptides or their secondary metabolic products. Human gut microbiota communicates with other organs through metabolites generated by the microbes or co-metabolized with the host. Whether the anti-hyperuricemia effect could be partially ascribed to the microbiota metabolites also deserves to be discussed. Although metabolomics analysis was performed for serum samples, fecal metabolomics was highly advocated which could facilitate exact mechanism explanation. This study implied that gut microbiota contains many unexplored targets with different therapeutic potentials. It is foreseeable that utilizing these targets can avoid the impairment or side effects of directly using human targets to some extent.

Ellagic acid alleviates high-fructose diet-induced non-alcoholic fatty liver disease by modulating liver metabolic profiles and gut microbiota

This study integrated analyses of gut microbiota and metabolomics to investigate the impact of ellagic acid (EA) on non-alcoholic fatty liver disease (NAFLD). Compared to the high-fructose diet (HFruD) group, the EA group exhibited reduced body weight and fat mass, alongside improvements in blood glucose and lipid metabolism. Liver metabolomics analysis revealed that EA increased the abundance of metabolites in pathways related to unsaturated fatty acids, amino acids and bile acids. Furthermore, EA induced alterations in the composition and structure of gut microbiota, notably decreasing bacterial genera enriched by HFruD while promoting beneficial bacteria such as Faecalibaculum. Correlation analysis demonstrated significant associations among NAFLD markers, gut microbiota and liver metabolites influenced by EA. This study provides new insights into the anti-NAFLD effects of EA, suggesting EA as a promising nutraceutical for improving NAFLD.

Therapeutic potential of Xihuang Pill in colorectal cancer: Metabolomic and microbiome-driven approaches

IntroductionThe Xihuang Pill (XHP), a venerated traditional Chinese medicine, has demonstrated significant anti-cancer capabilities. Despite its proven efficacy, the scarcity of comprehensive pharmacological studies limits the widespread application of XHP. This research endeavor seeks to demystify the therapeutic underpinnings of XHP, particularly in the realm of colorectal cancer (CRC) therapy.MethodsIn this study, mice harboring CT26 tumors were divided into four groups, each administered with either XHP monotherapy, 5-fluorouracil (5-FU), or a combination of both. The tumor growth trajectory was closely monitored to evaluate the effectiveness of these anti-neoplastic interventions. Advanced techniques, including 16S-rDNA gene sequencing and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), were harnessed to scrutinize the gut microbiota and serum metabolite profiles. Immunohistochemical assays were employed to gauge the expression levels of CD4, CD8, and Foxp3, thereby providing insights into the dynamics of tumor-infiltrating lymphocytes within the tumor microenvironment.ResultsOur findings indicate that XHP effectively suppresses the initiation and progression of colorectal tumors. The combinatorial therapy of XHP with 5-FU exhibited an enhanced inhibitory effect on tumor growth. Metabolic profiling revealed that XHP induced notable metabolic shifts, particularly impacting pathways such as steroid hormone synthesis, arachidonic acid metabolism, purine biosynthesis, and renin secretion. Notably, 17α-ethinyl estradiol and α-ergocryptine were identified as serum metabolites with the most substantial increase following XHP administration. Analysis of the gut microbiome suggested that XHP promoted the expansion of specific bacterial taxa, including Lachnospiraceae_NK4A136_group, Clostridiales, Desulfovibrionaceae, and Anaerotignum_sp., while suppressing the proliferation of others such as Ligilactobacilus, Lactobacillus_taiwanensis, and Candidatus_saccharimonas. Immunohistochemical staining indicated an upregulation of CD4 and CD8 post-XHP treatment.ConclusionThis study delineates a potential mechanism by which XHP inhibits CRC tumorigenesis through modulating the gut microbiota, serum metabolites, and reshaping the tumor immune microenvironment in a murine CRC model. These findings contribute to a more profound understanding and potentially broaden the clinical utility of XHP in oncology.

Altered intestinal microbiota and fecal metabolites in patients with latent and active pulmonary tuberculosis.

Pulmonary tuberculosis (PTB) is the main cause of infection-related mortality and the most common infectious disease that develops resistance to antibiotics. Gut microbiota and their associated metabolites are assumed to induce and influence the development of PTB. However, the alterations of gut microbiota and metabolites in TB patients is currently unclear. Fecal samples were collected from 13 PTB patients, 13 LTBI patients, and 13 healthy controls (HC). 16S rRNA sequencing and metabolomics were used to analyze the changes in the intestinal microbiota and the composition of fecal metabolites in groups. Our findings indicated that the α-diversity of the gut microbiota in patients with PTB and LTBI decreases compared to HC, and at the phylum level, the relative abundance of Firmicutes decreases and the relative abundance of Bacteroides increases. And six genera were notably enriched in PTB patients and four in LTBI patients. Metabolomic analysis showed alterations in metabolite levels, such as short-chain fatty acids and amino acids. we comprehensively explored the changes in the gut microbes and fecal metabolites in patients with PTB and LTBI from the perspective of the gut microbiota, which may provide potential diagnostic biomarkers and therapeutic targets for TB diagnosis and treatment.

Guidance and position of RINN22 regarding precision nutrition and nutriomics.

Precision nutrition is based on the integration of individual´s phenotypical and biological characteristics including genetic variants, epigenetic marks, gut microbiota profiles and metabolites fingerprints as well as medical history, lifestyle practices, and environmental and cultural factors. Thus, nutriomics areas including Nutrigenomics, Nutrigenetics, Nutriepigenetics, Nutrimetabolomics, and Nutrimetagenomics have emerged to comprehensively understand the complex interactions between nutrients, diet, and the human body's molecular processes through precision nutrition. This document from the Ibero-American Network of Nutriomics and Precision Nutrition (RINN22; https://rinn22.com/) provides a comprehensive overview of the concepts of precision nutrition approaches to guide their application in clinical and public health as well as establish the position of RINN22 regarding the current and future state of precision nutrition. The progress and participation of nutriomics to precision nutrition is an essential pillar for addressing diet-related diseases and developing innovative managing strategies, which will be promoted by advances in bioinformatics, machine learning and integrative software as well as the description of specific novel biomarkers. In this context, synthesizing and critically evaluating the latest developments, potential applications and future needs in the field of nutrition is necessary with a holistic perspective, incorporating progress in omics technologies aimed at precision nutrition interventions. This approach must address and confront healthy, social, food security, physically active lifestyle, sanitation and sustainability challenges with preventive, participatory, and predictive strategies of personalized, population and planetary nutrition for a precision tailored health.

Mechanism of Atractylenolide Ⅲ alleviating pyrotinib-induced diarrhea by regulating AMPK/CFTR pathway through metabolite of gut microbiota

Atractylenolide III, a sesquiterpene extracted from the rhizome of Atractylodes macrocephala (Asteraceae), exhibits pharmacological effects, including improvement of gastrointestinal function, regulation of immune function, anti-inflammatory and antibacterial properties. Pyrotinib, a representative TKI originally developed in China, is classified as a Class 1.1 novel drug, exhibits superior efficacy compared to similar drugs. Notably, the overall incidence of pyrotinib-induced diarrhea stands at 95 %, with 40 % of cases classified as grade ≥3 diarrhea. Currently, the effect of Atractylenolide III on pyrotinib-induced diarrhea and the underlying mechanisms remain unclear. Therefore, in this study, we established a pyrotinib (80 mg/kg/day) Wistar rat diarrhea model to explore the effect of Atractylenolide III on pyrotinib-induced diarrhea. We exploded the potential mechanism of Atractylenolide III via MQAE chloride fluorescent probe, RT-qPCR, Western blot, 16S rRNA sequencing, metabolomics, etc. We found that Atractylenolide III demonstrated the ability to alleviate pyrotinib-induced diarrhea without compromising its anti-tumor effects, inhibited pyrotinib-induced chloride secretion, and the potential mechanism of action involved enhancing AMPK phosphorylation while decreasing CFTR protein expression. Additionally, Atractylenolide III alleviated pyrotinib-induced diarrhea by modulating intestinal flora structure and increasing lithocholic acid content. This study could provide potential novel traditional Chinese medicine targets for treating diarrhea caused by tyrosine kinase inhibitor drugs, such as pyrotinib. The study emphasizes the role of TCM in minimizing adverse effects during tumor treatment.

Effects of Saccharomyces boulardii on microbiota composition and metabolite levels in the small intestine of constipated mice

Saccharomyces boulardii (S. boulardii) is a fungal probiotic used to treat digestive disorders. However, the mechanism(s) by which S. boulardii affects the small intestine remains unclear. Here, we aimed to explore the effects of S. boulardii on the small intestine and the underlying mechanisms in mice with loperamide-induced constipation. While S. boulardii administration did not fully reverse the alterations in loperamide-induced defecation parameters, it altered the small intestinal floral composition toward a community conducive to alleviate constipation. Moreover, S. boulardii up-regulated the expression of tyrosine-protein kinase Kit (c-Kit), aquaporin 3 (AQP3), interleukin (IL)-10, myosin light chain kinase (MLCK), and phosphorylated myosin light chain 20 (P-MLC20), while concurrently down-regulating the expression levels of inducible nitric oxide synthase (iNOS), p65, and IL-17 A. These alterations indicate a discernible effect of small intestinal water reabsorption, inflammatory factor levels, and smooth muscle contraction. Saccharomyces boulardii also positively regulated small intestinal metabolite levels, such as fructose 6-phosphate, dihomo-alpha-linolenic acid, and 3-(4-hydroxyphenyl) lactate, and participated in metabolic pathways such as arginine biosynthesis, linoleic acid metabolism, and protein digestion and absorption. While not fully reversing defecation changes, Saccharomyces boulardii alters intestinal flora, up-regulates key proteins affecting water reabsorption and inflammation, and positively influences metabolic pathways. Our study provides serves as a basis for further studies on the application of S. boulardii in the treatment of intestinal disorders.

Characteristic alterations of gut microbiota and serum metabolites in patients with chronic tinnitus: a multi-omics analysis.

Chronic tinnitus is a central nervous system disorder. Currently, the effects of gut microbiota on tinnitus remain unexplored. To explore the connection between gut microbiota and tinnitus, we conducted 16S rRNA sequencing of fecal microbiota and serum metabolomic analysis in a cohort of 70 patients with tinnitus and 30 healthy volunteers. We used the weighted gene co-expression network method to analyze the relationship between the gut microbiota and the serum metabolites. The random forest technique was utilized to select metabolites and gut taxa to construct predictive models. A pronounced gut dysbiosis in the tinnitus group, characterized by reduced bacterial diversity, an increased Firmicutes/Bacteroidetes ratio, and some opportunistic bacteria including Aeromonas and Acinetobacter were enriched. In contrast, some beneficial gut probiotics decreased, including Lactobacillales and Lactobacillaceae. In serum metabolomic analysis, serum metabolic disturbances in tinnitus patients and these differential metabolites were enriched in pathways of neuroinflammation, neurotransmitter activity, and synaptic function. The predictive models exhibited great diagnostic performance, achieving 0.94 (95% CI: 0.85-0.98) and 0.96 (95% CI: 0.86-0.99) in the test set. Our study suggests that changes in gut microbiota could potentially influence the occurrence and chronicity of tinnitus, and exert regulatory effects through changes in serum metabolites. Overall, this research provides new perceptions into the potential role of gut microbiota and serum metabolite in the pathogenesis of tinnitus, and proposes the "gut-brain-ear" concept as a pathomechanism underlying tinnitus, with significant clinical diagnostic implications and therapeutic potential.IMPORTANCETinnitus affects millions of people worldwide. Severe cases may lead to sleep disorders, anxiety, and depression, subsequently impacting patients' lives and increasing societal healthcare expenditures. However, tinnitus mechanisms are poorly understood, and effective therapeutic interventions are currently lacking. We discovered the gut microbiota and serum metabolomics changes in patients with tinnitus, and provided the potential pathological mechanisms of dysregulated gut flora in chronic tinnitus. We proposed the innovative concept of the "gut-brain-ear axis," which underscores the exploration of gut microbiota impact on susceptibility to chronic tinnitus through serum metabolic profile modulation. We also reveal novel biomarkers associated with chronic tinnitus, offering a new conceptual framework for further investigations into the susceptibility of patients, potential treatment targets for tinnitus, and assessing patient prognosis. Subsequently, gut microbiota and serum metabolites can be used as molecular markers to assess the susceptibility and prognosis of tinnitus.Furthermore, fecal transplantation may be used to treat tinnitus.

Astragalus polysaccharide alleviates asthma by modulating gut microbiota and serum metabolomics.

The aim of the present study was to examine the effects of Astragalus polysaccharide (APS) on gut microbiota and serum metabolites in asthmatic mice. For this purpose, a total of 36 BALB/c female mice were selected and randomly classified into the following groups: i) The normal control group sensitized with phosphate-buffered saline; ii) the asthma group sensitized and challenged with ovalbumin (OVA); iii) the OVA + APS (2.5 g/kg) treatment group; iv) the OVA + APS (5.0 g/kg) treatment group; v) the OVA + APS (10 g/kg) treatment group; and vi) the OVA + dexamethasone (2 mg/kg) treatment group, with 6 mice in each group. OVA was used to establish the mouse model of asthma. In the APS group, the asthmatic mice were intragastrically administered APS at various doses at 1 h prior to each OVA stimulation. The airway hyperreactivity (AHR) was measured, and hematoxylin and eosin staining was employed to evaluate pulmonary inflammatory infiltration. In addition, 16S rRNA sequencing and ultra-performance liquid chromatography-tandem mass spectrometry were used to detect the changes in the mouse gut microbiota and serum metabolites. The results revealed that compared with the asthma model group, APS improved airway inflammation and eosinophil infiltration in asthmatic mice. In asthmatic mice, the gut microbial imbalance mainly manifested as a low abundance of Bacteroidetes and a high abundance of Firmicutes, yielding an increased F/B ratio. In the high-dose APS group, the abundance of Firmicutes was reduced, and the abundance of Bacteroidetes was increased, which thereby decreased the F/B ratio and corrected the gut microbial imbalance. Through blood metabolomics, 145 and 105 significantly differential metabolites were detected in the medium- and high-dose APS groups, respectively. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis demonstrated that the metabolic pathways in the medium-dose APS group included the biosynthesis of unsaturated fatty acids and the biosynthesis of arginine. On the other hand, the metabolic pathways enriched in high-dose APS group were the biosynthesis of unsaturated fatty acids, and pyrimidine metabolism. On the whole, the present study demonstrates that APS may regulate the gut microbiota and the metabolites to improve airway inflammation and AHR in asthmatic mice.

Herbal formula xuling-jiangu improves bone metabolic balance in rats with ovariectomy-induced osteoporosis via the gut-bone axis.

The XuLing JianGu recipe (XLJGR) is an empirical traditional Chinese medicine formula used for the treatment of osteoporosis. This study aims to explore the effects of XLJGR on the intestinal microbiota composition and endogenous metabolites in ovariectomized (OVX) rats. An OVX rat model was established to evaluate the intervention effects of XLJGR. The measured indicators included bone density, serum bone metabolism markers, and an analysis of the types and abundances of intestinal microbiota, along with changes in endogenous metabolites. Additionally, MC3T3-E1 cells were used to validate the differential metabolites. XLJGR significantly reduced the abundance of Bacteroides, Butyricicoccus, and other bacterial strains in the gut. KEGG metabolic pathway enrichment analysis showed that XLJGR intervention led to notable changes in pathways such as peptidoglycan biosynthesis, carbapenem biosynthesis, and vancomycin resistance. Moreover, XLJGR significantly upregulated key intestinal microbiota metabolites, including gabapentin(GAB), camphoric acid(CAA), and nonanedioic acid(AZA), thereby promoting the proliferation and osteogenic differentiation of MC3T3-E1 cells. This study highlights the potential biomedical applications of XLJGR in promoting bone health by positively affecting intestinal microbiota and metabolic characteristics. These findings suggest that XLJGR may serve as a viable alternative in the treatment of osteoporosis, warranting further exploration of its therapeutic mechanisms and clinical applications.

Association analysis of gut microbiota with LDL-C metabolism and microbial pathogenicity in colorectal cancer patients

BackgroundColorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression.MethodsThis study thoroughly examined the gut microbiota through 16S rRNA sequencing of fecal samples from 181 CRC patients, integrating preoperative Low-density lipoprotein cholesterol (LDL-C) levels and RNA sequencing data. The study includes a comparison of microbial diversity, differential microbiological analysis, exploration of the associations between microbiota, tumor microenvironment immune cells, and immune genes, enrichment analysis of potential biological functions of microbe-related host genes, and the prediction of LDL-C status through microorganisms.ResultsThe analysis revealed that differences in α and β diversity indices of intestinal microbiota in CRC patients were not statistically significant across different LDL-C metabolic states. Patients exhibited varying LDL-C metabolic conditions, leading to a bifurcation of their gut microbiota into two distinct clusters. Patients with LDL-C metabolic irregularities had higher concentrations of twelve gut microbiota, which were linked to various immune cells and immune-related genes, influencing tumor immunity. Under normal LDL-C metabolic conditions, the protective microorganism Anaerostipes_caccae was significantly negatively correlated with the GO Biological Process pathway involved in the negative regulation of the unfolded protein response in the endoplasmic reticulum. Both XGBoost and MLP models, developed using differential gut microbiota, could forecast LDL-C levels in CRC patients biologically.ConclusionsThe intestinal microbiota in CRC patients influences the LDL-C metabolic status. With elevated LDL-C levels, gut microbiota can regulate the function of immune cells and gene expression within the tumor microenvironment, affecting cancer-related pathways and promoting CRC progression. LDL-C and its associated gut microbiota could provide non-invasive markers for clinical evaluation and treatment of CRC patients.

Navigating contradictions: Salmonella Typhimurium chemotactic responses to conflicting effector stimuli.

Chemotaxis controls swimming motility and colonization of many intestinal bacteria, but how enteric pathogens navigate the complex chemical landscape of the gut, which contains contradictory chemoattractant and chemorepellent stimuli, remains poorly understood. We find Salmonella Typhimurium requires chemotactic sensing of two opposing signals present in the intestinal lumen-the microbiota metabolite and bacteriostatic chemorepellent indole, and the nutrient chemoattractant L-Ser-for efficient invasion of colonic tissue. Despite feces being the major biological source of indole, accumulating to millimolar levels, non-typhoidal Salmonella are strongly attracted to fecal material because chemoattraction to L-Ser and other attractants override indole chemorepulsion. This behavior is orchestrated through the chemoreceptor Tsr, which coordinates a spectrum of distinct rearrangements in the bacterial population structure based on the ratio of L-Ser to indole. Through seeking niches with the highest L-Ser to indole ratio, S. Typhimurium presumably optimizes nutrient access and avoids regions of high-competitor density.

Exploring bacterial metabolites in microbe-human host dialogue and their therapeutic potential in Alzheimer's diseases.

Neurological dysfunction in association with aging, dementia, and cognitive impairment is the major cause of Alzheimer's disease (AD). Current AD therapies often yield unsatisfactory results due to their poor mechanism in treating the underlying mechanism of the disease. Recent studies suggested that metabolites from the gut microbiota facilitate brain-gut communication. A systematic network pharmacology study and the structure- and analog-based approaches are employed to investigate the metabolites produced by gut microbiota to treat AD. The microbiota metabolites available in the gutMGene database were considered in this study. Two servers, namely Swiss Target Prediction (STP) and Similarity Ensemble Approach (SEA), were used to identify the possible AD targets for the selected metabolites. Detailed KEGG pathway and Gene Ontology (GO) analysis on identified hub genes highlighted the importance of IL6, AKT1, and GSK3B in AD pathophysiology. MMTSp (Microbiota Metabolites Target Signaling pathways) network analysis elucidated that there is a strong relationship with microbiota (Paraprevotella xylaniphila YIT 11841, Bifidobacterium dentium, Paraprevotella clara YIT 11840, Enterococcus sp. 45, Bacteroides sp. 45, Bacillus sp. 46, Escherichia sp. 33, Enterococcus casseliflavus, Bacteroides uniformis, Alistipes indistinctus YIT 12060, Bacteroides ovatus, Escherichia sp. 12, and Odoribacter laneus YIT 12061) and AD pathogenesis. In addition to this, we performed molecular docking to study the metabolite interactions in the AD drug targets. The ADME/T properties of these metabolites were also calculated and the results are discussed in detail.

Role of blood metabolites in mediating the effect of gut microbiota on chronic gastritis.

Exploring the link between gut microbiota and chronic gastritis (CG), and assessing the potential mediating influence of blood metabolites. Using aggregated data from genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to explore the genetic links between gut microbiota (412 types) and CG (623,822 cases). Furthermore, we utilized a two-step MR approach to measure the extent to which blood metabolites (1,400 types) mediate the impact of gut microbiota on CG. Through MR, we identified that three genetically predicted gut microbiota increased the risk of CG: the ubiquinol-8 biosynthesis pathway (OR 1.149, 95%CI 1.022-1.291), Odoribacter from the Porphyromonadaceae family (OR 1.260, 95%CI 1.044-1.523), and Coprococcus from the Lachnospiraceae family (OR 1.125, 95%CI 1.010-1.253). Currently, there is no evidence to suggest that genetically predicted CG affects the risk of gut microbiota. Four blood metabolites mediated the proportionate changes in genetically predicted gut microbiota: levels of 4-hydroxyphenylacetate levels by 14.9% (95% CI -0.559%, 30.3%), palmitoleate (16:1n7) levels, and the phosphate to alanine ratio together mediated the same microbiota by 6.97% (95% CI -1.61%, 15.6%) and 7.91% (95% CI -1.67%, 17.5%), while the phosphate to alanine ratio and X-12839 levels together mediated the same microbiota by 8.48% (95% CI -2.87%, 19.8%) and 10.7% (95% CI 0.353%, 21.1%). In conclusion, our research has confirmed a causal link between gut microbiota, blood metabolites, and CG. Metabolites such as 4-hydroxyphenylacetate levels, palmitoleate (16:1n7) levels, the phosphate to alanine ratio, and X-12839 levels have relatively significant mediating roles between gut microbiota and CG. These metabolites may influence the occurrence and development of CG by regulating inflammatory responses, energy metabolism, and gut barrier function. However, the majority of the influence of gut microbiota on CG remains unclear, necessitating further research into other potential mediating risk factors. Clinically, it is crucial to focus on patients suffering from CG who exhibit dysbiosis of gut microbiota.IMPORTANCEThe results indicate that interactions between particular gut microbiota and blood metabolites may significantly contribute to the onset and progression of CG. These findings offer new insights and potential targets for early diagnosis, personalized treatment, and prevention of CG.

Gut microbiota and metabolomics unveil the mechanisms of Lomatogonium rotatum in ameliorating visceral fat and serum lipids in high-fat diet-induced obese mice.

Lomatogonium rotatum (LR) is a folk medicinal herb traditionally used as a lipid-lowering and anti-obesity agent; but its pharmacological mechanism is unclear. In this study, we assessed the alterations of LR on gut microbes and serum metabolites in obese mice and their associated mechanisms of modulation on visceral fat and serum lipid by integrating gut microbiota and metabolomics analyses. Mice were fed a high-fat diet (HFD) to generate obesity and were then given LR and Orlistat orally at different doses (0.18, 0.9, 1.8g/kg for LR and 0.048g/kg for Orlistat) for a duration of 9weeks. The impact of LR on weight loss was assessed through the examination of fat deposition, serum lipid indices, liver indices, and HE pathohistology. The effects of LR on gut microbiota and serum metabolites in obese mice were then investigated by 16S rRNA sequencing technology and untargeted metabolomics, and correlation analysis was performed. LR significantly reduced body weight, feed intake, Lee's index, visceral fat accumulation, serum TG, TC, AST and ALT, and elevated serum HDL levels in obese mice. In addition, 16S rRNA sequencing results indicated that the LR intervention remodeled microbial diversity and composition, increased the relative abundance of gut microbes Bacteroidetes and Porphyromonadaceae in HFD-induced obese mice, and decreased the Deferribacteres, Firmicutes and the Firmicutes/Bacteroidetes ratio. Correlation analyses showed that LR regulation of L-tyrosine and hesperetin metabolism, as well as alterations in the metabolic pathways of Phenylalanine, tyrosine and tryptophan biosynthesis, were associated with the changes in abundance of Bacteroidetes, Firmicutes, Porphyromonadaceae and Deferribacteres. Our study demonstrated that LR has lipid lowering and visceral fat reduction effects and its function may be closely related to the improvement of the gut microbiota and its associated metabolites.

A polysaccharide from edible red seaweed Bangia fusco-purpurea prevents obesity in high-fat diet-induced C57BL/6 mice

The study aimed to investigate the impacts of a polysaccharide (BFP) from Bangia fusco-purpurea on high-fat diet (HFD)-induced obesity in C57BL/6 mice, as well as its underlying mechanisms. Our results showed that orally administrated BFP was more effective than inulin (INU) in reducing body weight and fat accumulation in obese mice, indicating its anti-obesity effect. BFP effectively improved the compositions and metabolites of intestinal microbiota in obese mice, leading to enhanced energy metabolism and lipid metabolism, thus contributing to its anti-obesity effect. Notably, the better anti-obesity effect of BFP compared to INU were attributed to their varying degrees of modulation of specific intestinal microbial taxa, such as Clostridium and Aerococcus, as well as the regulation of differential metabolites (including biotin, piperine, G6P, etc.) also varies. Also, both in vitro (3T3-L1 preadipocytes) and in vivo (HFD-induced obese mice) models confirmed that BFP achieved anti-obesity effect attributed to enhance energy metabolism, promote lipolysis, increase fatty acid oxidation, and inhibit adipogenesis via activating the AMP-activated protein kinase and Acetyl-CoA carboxylase signaling pathways and suppressing the peroxisome proliferator-activated receptor γ expression. Our findings suggest that BFP has the potential to be used as prebiotics, dietary agents, and nutritional supplements against obesity.

Dietary β-hydroxybutyrate sodium alters rumen microbiome and nutrient metabolism in the rumen epithelium of young goats

The role of β-hydroxybutyric acid (BHBA) includes providing energy, regulating signaling pathways, and ameliorating the gut microbiota in the host, while its nutrient mechanism to improve rumen epithelium development in young ruminants is still unclear. In this study, a total of 12 female Haimen goats with 30 days of age were chosen and divided into two groups. One group was fed with basic diet (CON), and the other group was fed a basal diet supplemented with 6 g d-1 dietary β-hydroxybutyrate sodium (BHBA-Na). The experimental period was 30 days, and all goats were slaughtered at 60 days of age. The joint analysis of multi-omics, including rumen microbiota, rumen epithelial transcriptome and rumen epithelial metabolomics in young goat model, was performed to systematically investigate the effect of dietary BHBA-Na on rumen development in young goats. As the results, we found that dietary BHBA-Na improved the growth performance of young goat including body weight, average daily gain (ADG) and dry matter intake (DMI) (P<0.05). Dietary BHBA-Na also increased the weight of rumen, and promoted the growth of rumen epithelium development (P < 0.05). The abundance of several beneficial bacteria was increased (Fibrobacter, Succinivibrio, Clostridiales, etc.,). The rumen epithelium transcriptome and metabolomics indicated that BHBA-Na supplementation showed a remarkable effect on the nutrient metabolism of the rumen epithelium. Specifically, the pathways of “fatty acid metabolism”, “cholesterol homeostasis”, “reactive oxygen species (ROS) pathway” and “peroxisome” were activated in response to BHBA-Na addition (P < 0.05). Moreover, the genes (HMGCS2, ECSH1, ACAA2, ECH1, ACADS etc.) and metabolites (succinic acid, alpha-ketoisovaleric acid, etc.) involved in these pathways were also regulated positively (P < 0.05). The rumen epithelium obtained the energy for its development from the process of volatile fatty acids (VFAs) decomposition. Finally, we observed the close correlations among the phenotypes, ruminal microbiota, host genes and epithelial metabolites. Overall, our results revealed that the BHBA-Na promoted the growth and rumen development of young goats possibly by enhancing DMI and regulating the rumen microbiota and the metabolisms of VFA and amino acid in the rumen epithelium.

Chromium yeast promotes milk protein synthesis by regulating ruminal microbiota and amino acid metabolites in heat-stressed dairy cows

The intensifying global warming may increase the impact of heat stress on the dairy industry. Our previous study showed that chromium yeast (CY) alleviated the negative effects of heat stress and improved the lactation performance by increasing milk protein content and yield in mid-lactation dairy cows. This study further investigated whether the increased milk protein after CY supplementation results from the promotion of microbial crude protein (MCP) synthesis by regulating rumen microorganisms and amino acid metabolites. Twelve heat-stressed dairy cows were divided into two treatment groups: one with CY supplementation (0.36 mg Cr/kg DM) and the other without CY supplementation. Samples were collected after eight weeks of formal experiment in a hot summer with the mean temperature-humidity index of 79.0 ± 3.13. Dietary CY supplementation did not affect rumen pH, total volatile fatty acid, acetate, propionate, isobutyrate, butyrate, isovalerate, and valerate, but increased ruminal MCP concentration (P < 0.05). Simultaneously, the alpha or beta diversity of rumen microbial bacteria were not influenced by CY supplementation. At genus level, supplementation with CY increased the relative abundances of Olsenella, Lachnospiraceae_UCG-002, and Shuttleworthia (P < 0.05) and decreased those of Enterobacter, Escherichia-Shigella, Oribacterium, and Bacteroidetes_BD2-2 (P < 0.05). There were 17 up-regulated and 57 down-regulated differential metabolites in the CON and CY groups. The partial least-squares discriminant analysis (PLS-DA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) scores clearly distinguished the two groups. Chromium yeast supplementation reduced the concentrations of D-(+)-proline, DL-glutamic acid, DL-lysine, Gly-l-pro, L-(-)-serine, L-(+)-alanine, and L-(+)-aspartic acid (P < 0.05) in the ruminal fluid, which were involved in arginine biosynthesis (P = 0.029), glutathione metabolism (P = 0.047), lysine degradation (P = 0.069), and D-amino acid metabolism (P = 0.084). Spearman correlation analysis showed that milk protein content was positively correlated with MCP and negatively correlated with amino acid concentrations in the ruminal fluid (P < 0.05). Collectively, CY supplementation promoted the utilization of amino acids by rumen microorganisms to synthesize MCP, thereby increasing milk protein content and yield in heat-stressed dairy cows.

Alterations in Gut Microbiota and Serum Metabolites in Children with Mycoplasma pneumoniae Pneumonia.

Over the past years, there has been a significant increase in the incidence of Mycoplasma pneumoniae (MP) infections, particularly among pediatric patients, nationwide. An emerging body of research has established a link between dysbiosis of the host microbiome and the metabolic functioning of the host, which contributes to the development of respiratory diseases. A total of 25 children were included in the study, comprising 15 pneumonia patients and 10healthy children. Stool samples were collected from all participants to analyze the 16S ribosomal RNA (16S rRNA) gene, while serum samples were prepared for untargeted metabolomics to qualitatively and quantitatively assess short-chain fatty acids. The gut microbial composition of individuals with Mycoplasma pneumoniae pneumonia (MPP) exhibited significant differences compared to healthy children. Notably, diseased children demonstrated higher microbial diversity and an enrichment of opportunistic pathogens, such as Erysipelatoclostridium and Eggerthella. Analysis revealed elevated levels of two specific short-chain fatty acids, namely acetic acid and isobutyric acid, in the MPP group, suggesting their potential as biomarkers for predicting MP infection. Metabolomic signature analysis identified a significant increase in major classes of glycerophospholipids in the MPP group. Moreover, we identified a total of 750 significant correlations between gut microbiota and circulating serum metabolites. MPP enriched genera Erysipelatoclostridium and Eggerthella, exhibited negative associations with indole-3-butyric acid. Additionally, Eggerthella showed a positive correlation with inflammatory metabolites LPC (18:0). Collectively, these findings provide novel insights into the selection of potential biomarkers and the pathogenesis of MPP in children based on the gut microbiota and systemic circulating metabolites.

Gut microbiota combined with metabolome dissects Fluorene-9-bisphenol exposure-induced male reproductive toxicity

A major alternative to bisphenol A (BPA), fluorene-9-bisphenol (BHPF) has been shown to cause multiorgan toxicity. However, its reproductive toxicity and the underlying biological mechanism remain largely unknown. Recently, changes in the gut microbiota and metablome caused by environmental contaminant exposure and their potential impact on male reproductive health have been of great concern. Therefore, we aimed to elucidate the underlying mechanism of BHPF-related fertility impairment by integrating metabolome and microbiome analysis. In the present study, we showed that BHPF exposure caused testicular dysfunction with impaired spermatogenesis and disrupted steroid hormone synthesis. Mechanistically, altered gut microbiota and metabolites were revealed by 16S rDNA sequencing and untargeted metabolomics analysis. Subsequent multi-omics combination analysis revealed a strong correlation between altered microbiota and lipid metabolites. We also found a strong relationship between lipid metabolites and sperm parameters such as sperm concentration, sperm motility, etc. Most importantly, these findings provide new insights into the mechanistic scenario underlying BHPF-induced fertility toxicity, that disrupted lipid metabolism caused by gut microbiota dysbiosis may be a reason for reproductive impairment caused by BHPF exposure.