Fecal Metabolome Research Articles

Altered gut microbiota and metabolites in untreated myasthenia gravis patients.

The homeostasis of the immune system is influenced by the gut microbiota. Previous studies have reported dysbiosis in the gut microbiota of myasthenia gravis (MG) patients. To investigate potential alterations in gut microbiota and metabolites in newly diagnosed and untreated MG patients, we conducted a case-control study. Fecal samples were collected from 11 newly diagnosed and untreated MG patients as well as 11 age-and sex-matched healthy controls. These samples underwent analysis for gut microbiota using 16S ribosomal RNA (rRNA) gene sequencing, while fecal metabolome was analyzed using liquid chromatography-electrospray tandem mass spectrometry system (LC-ESI-MS/MS). The microbial community richness (observed species) and diversity (Shannon and Simpson indices) were significantly lower in the MG group compared to the control group. Microbiota composition analysis revealed significant differences between the MG and control groups at phylum, family, and genus levels. Linear discriminant analysis effect size (LEfSe) analysis showed a substantial decrease in abundance of the genus Faecalibacterium within the MG group. Fecal metabolome analysis identified three up-regulated metabolites involved in amino acid metabolism (taurine, creatinine, L-carnitine), one up-regulated metabolite involved in lipid metabolism (oleic acid), with correlation analysis indicating a positive association between Faecalibacterium abundance and creatinine levels. Our findings suggest that dysbiosis already exists in newly diagnosed and untreated MG patients, implying that dysbiosis within the gut microbiota may be an initiating factor contributing to MG pathogenesis. Furthermore, F. prausnitzii may hold promise as a probiotic for treating MG.

Alterations of fecal microbiome and metabolome in pemphigus patients

The role of gut microbiome and metabolic substances in the development of autoimmune diseases has gradually been revealed. However, the relevant gut features in pemphigus have not been well clarified. We collected stool samples from pemphigus patients and healthy controls (HCs). Metagenomic sequencing and liquid chromatography-mass spectrometry (LC/MS) metabolome sequencing were performed to analyze the compositional and metabolic alternations of the gut microbiome in pemphigus patients and HCs. We observed the reduced richness and diversity and greater heterogeneity in pemphigus patients, which was characterized by a significant decrease in Firmicutes and an increase in Proteobacteria. At the species level, Intestinal pathogenic bacteria such as Escherichia coli and Bacteroides fragilis were significantly enriched, while anti-inflammatory bacteria and butyric acid-producing bacteria were significantly reduced, which were related to clinical indicators (Dsg1/3 and PDAI). 4 species were selected by the machine learning algorithm to better distinguish pemphigus patients from healthy people. Metabolomic analysis showed that the composition of pemphigus patients was different from that of HCs. PE (18:3 (6Z,9Z, 12Z)/14:1 (9Z)) was the main metabolic substance in pemphigus and involved in a variety of metabolic pathways. While Retinol, flavonoid compounds and various amino acids decreased significantly compared with HCs. Furthermore, we found that differences in the levels of these metabolites correlated with changes in the abundance of specific species. Our study provides a comprehensive picture of gut microbiota and metabolites in pemphigus patients and suggests a potential mechanism of the aberrant gut microbiota and metabolites in the pathogenesis of pemphigus.

Efficacy and mechanism study of Baichanting compound, a combination of Acanthopanax senticosus (Rupr. and Maxim.) Harms, Paeonia lactiflora Pall and Uncaria rhynchophylla (Miq.) Miq. ex Havil, on Parkinson's disease based on metagenomics and metabolomics

Ethnopharmacological relevanceParkinson's disease (PD) is a rapidly progressing neurological disorder. Currently, Medication for PD has numerous limitations. Baichanting Compound (BCT) is a Chinese herbal prescription, a Combination of Acanthopanax senticosus (Rupr. and Maxim.) Harms, Paeonia lactiflora Pall and Uncaria rhynchophylla (Miq.) Miq. ex Havil, that was developed to treat PD and holds a national patent (ZL, 201110260536.3). Aim of the studyTo clarify the therapeutic effect of BCT on PD and explore its possible mechanism based on metabolomics and metagenomics. Materials and methodsC57BL/6 mice were used as a control group, and α-syn transgenic C57BL/6 mice were randomly assigned to the PD (without treatment) or BCT (with BCT treatment) group. UPLC-MS was performed to detect dopamine levels in brain tissue, while ELISA was used to determine inflammatory factors such as IL-1β, IL-6, TNF-α, IFN-γ and NO, and oxidative stress indicators such as malondialdehyde, superoxide dismutase and glutathione peroxidase enzyme activity. Fecal metabolomics was used to detect fecal metabolic profiles, screen differential metabolic markers, and predict metabolic pathways by KEGG enrichment analysis. Metagenomics was used to determine the intestinal microbial composition, and KO enrichment analysis was performed to predict the potential function of different gut microbiota. Finally, Spearman correlation analysis was used to find the possible relationships among intestinal flora, metabolic markers, inflammatory factors, oxidative stress and dopamine levels. ResultsBCT increased the superoxide dismutase activity of α-Syn transgenic C57BL/6 mice (P < 0.01), decreased the levels of TNF-α, IFN-γ, IL-1β, IL-6, NO and malondialdehyde (P < 0.01, 0.05), and increased the release of dopamine (P < 0.01). Metabolomics results show that BCT could regulate Acetatifactor, Marvinbryantia, Faecalitalea, Anaeromassilibacillus, Anaerobium, Pseudobutyrivibrio and Lachnotalea and Acetatifactor_muris, Marvinbryantia_formatexigens, Lachnotalea_sp_AF33_28, Faecalitalea_sp_Marseille_P3755 and Anaerobium_acetethylicum, Gemmiger_sp_An120 abundance to restore intestinal flora function, and reverse fecal metabolism trend, restoring the content of α-D-glucose, cytidine, L-glutamate, L-glutamine, N-acetyl-L-glutamate, raffinose and uracil. In addition, it regulates arginine biosynthesis, D-glutamine and D-glutamate, pyrimidine, galactose and alanine, aspartate and glutamate metabolic pathways. ConclusionBCT may regulate the composition of the gut microbiota to reverse fecal metabolism in PD mice to protect the substantia nigra and striatum from oxidative stress and inflammatory factors and ultimately play an anti-PD role.

Effect of the Probiotic Bacillus subtilis DE-CA9TM on Fecal Scores, Serum Oxidative Stress Markers and Fecal and Serum Metabolome in Healthy Dogs.

There is increasing interest in the use of Bacillus species as probiotics since their spore-forming ability favors their survival in the acidic gastric environment over other probiotic species. The subsequent germination of B. subtilis to their vegetative form allows for their growth in the small intestine and may increase their beneficial effect on the host. B. subtilis strains have also previously been shown to have beneficial effects in humans and production animals, however, no reports are available so far on their use in companion animals. The goal of this study was therefore to investigate the daily administration of 1 × 109 cfu DE-CA9TM orally per day versus placebo on health parameters, fecal scores, fecal microbiome, fecal metabolomics, as well as serum metabolomics and oxidative stress markers in ten healthy Beagle dogs in a parallel, randomized, prospective, placebo-controlled design over a period of 45 days. DE-CA9TM decreased the oxidative status compared to controls for advanced oxidation protein products (AOPP), thiobarbituric acid reactive substances (TBARS) and reactive oxygen metabolites (d-ROMS), suggesting an antioxidant effect of the treatment. Fecal metabolomics revealed a significant reduction in metabolites associated with tryptophan metabolism in the DE-CA9TM-treated group. DE-CA9TM also significantly decreased phenylalanine and homocysteine and increased homoserine and threonine levels. Amino acid metabolism was also affected in the serum metabolome, with increased levels of urea and cadaverine, and reductions in N-acetylornithine in DE-CA9TM compared to controls. Similarly, changes in essential amino acids were observed, with a significant increase in tryptophan and lysine levels and a decrease in homocysteine. An increase in serum guanine and deoxyuridine was also detected, with a decrease in beta-alanine in the animals that ingested DE-CA9TM. Data generated throughout this study suggest that the daily administration of 1 × 109 cfu of DE-CA9TM in healthy Beagle dogs is safe and does not affect markers of general health and fecal scores. Furthermore, DE-CA9TM administration had a potential positive effect on some serum markers of oxidative stress, and protein and lipid metabolism in serum and feces.

Long-term and trimester-specific effects of prenatal stress on the child gut microbiota

ObjectiveStress is common among pregnant individuals and is associated with an altered gut microbiota composition in infants. It is unknown if these compositional changes persist into the preschool years when the gut microbiota reaches an adult-like composition. This study aimed to investigate if indicators of prenatal stress (i.e., psychological distress and stress-related physiology) are associated with children’s gut microbiota composition and metabolites at 3–4 years of age. MethodsMaternal-child pairs (n = 131) were from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort. Each trimester, psychological distress was measured as symptoms of anxiety (Symptom Checklist-90-R) and depressed mood (Edinburgh Postnatal Depression Scale), whereas salivary cortisol was quantified as a measure of stress-related physiology. Child stool samples were collected at 3–4 years to evaluate gut microbiota composition using 16S rRNA gene sequencing and fecal metabolome using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Associations between prenatal distress and cortisol with the gut microbiota were determined using Pearson and Spearman correlations and corrected for multiple testing. Associations between prenatal distress and cortisol with the fecal metabolome were assessed using Metaboanalyst. ResultsSymptoms of depressed mood during the 2nd and 3rd trimesters and anxiety during the 2nd trimester of pregnancy were associated with increased alpha diversity of the child’s gut microbiota. Cortisol levels during the 1st trimester were also associated with increased Faith PD diversity (r = 0.32), whereas cortisol levels during the 2nd trimester were associated with reduced Shannon diversity (r = −0.27). Depression scores during the 2nd and 3rd trimesters were associated with reductions in the relative abundances of Eggerthella, Parasutterella, and increases in Ruminococcaceae (rs = −0.28, rs = −0.32, rs = 0.32, respectively), as well as the fecal metabolome (e.g., branched-chain amino acid metabolism). Cortisol levels during the 2nd trimester correlated with 7 bacterial taxa, whereas 1st-trimester cortisol levels were associated with the child’s fecal metabolome. ConclusionsPrenatal distress and cortisol were associated with both child gut microbiota composition and fecal metabolome at preschool age. Understanding these associations may allow for the identification of microbiota-targeted interventions to support child developmental outcomes affected by prenatal stress.

Gut microbes consume host energy and reciprocally provide beneficial factors to sustain a symbiotic relationship with the host

The gut microbes thrive by utilizing host energy and, in return, provide valuable benefits, akin to the symbiotic relationship. To study the mutualistic association between the gut microbiota and host, a range of gut microbe populations (85 %, 66 %, 45 % and 38 % at the normal level) with comparable structures were constructed in broiler model. The results revealed that reductions in gut microbial population led to decreased energy consumption, resulting in increased host weight (10.26 %, 30.88 %, 17.65 % and − 12.77 %, respectively). Fecal metabolome revealed that among 85 % and 66 % of the normal population level, the gut microbes downregulated the immune-associated pathways of tryptophan metabolism and catecholamine biosynthesis, while the level of fatty acid oxidation was upregulated at 45 %. In the host, the concentration of gut microbes contributed to regulate functions related to lipid biosynthesis (from glycerophosphoserines to glycerophosphoethanolamines (9.63 %, 12.20 %, 6.66 % and 47.75 %) and glycerophosphocholines (10.78 %, 36.51 %, 2.00 % and 87.11 %)) and inflammation responses (methionine and betaine metabolism). From 85 % to 45 % of gut microbes, broiler showed an inhibited immunity (thymus gland, spleen, SIgG and IgA) and increased low-level inflammation response (ALT and T-SOD). However, at 38 %, the immune indexes exhibited an increase (thymus gland, spleen, SIgG, and IgA increased by 8.67 %, 8.50 %, 20.87 %, and 29.43 %, respectively), indicating the host lipid accumulation and inflammation response were negatively correlated with the immune reaction. Collectively, the gut microbiota maintains a symbiotic relationship with the host through the secretion of beneficial substances to interact with the host.

Gut microbes exacerbate systemic inflammation and behavior disorders in neurologic disease CADASIL

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that carries mutations in NOTCH3. The clinical manifestations are influenced by genetic and environmental factors that may include gut microbiome.ResultsWe investigated the fecal metagenome, fecal metabolome, serum metabolome, neurotransmitters, and cytokines in a cohort of 24 CADASIL patients with 28 healthy household controls. The integrated-omics study showed CADASIL patients harbored an altered microbiota composition and functions. The abundance of bacterial coenzyme A, thiamin, and flavin-synthesizing pathways was depleted in patients. Neurotransmitter balance, represented by the glutamate/GABA (4-aminobutanoate) ratio, was disrupted in patients, which was consistent with the increased abundance of two major GABA-consuming bacteria, Megasphaera elsdenii and Eubacterium siraeum. Essential inflammatory cytokines were significantly elevated in patients, accompanied by an increased abundance of bacterial virulence gene homologs. The abundance of patient-enriched Fusobacterium varium positively correlated with the levels of IL-1β and IL-6. Random forest classification based on gut microbial species, serum cytokines, and neurotransmitters showed high predictivity for CADASIL with AUC = 0.89. Targeted culturomics and mechanisms study further showed that patient-derived F. varium infection caused systemic inflammation and behavior disorder in Notch3R170C/+ mice potentially via induction of caspase-8-dependent noncanonical inflammasome activation in macrophages.ConclusionThese findings suggested the potential linkage among the brain-gut-microbe axis in CADASIL.99hFA7addb1qytHAFkqi-MVideo

Ootheca mantidis mitigates renal fibrosis in mice by the suppression of apoptosis via increasing the gut microbe Akkermansia muciniphila and modulating glutamine metabolism

Renal interstitial fibrosis (RIF), a progressive process affecting the kidneys in chronic kidney disease (CKD), currently lacks an effective therapeutic intervention. Traditional Chinese medicine (TCM) has shown promise in reducing RIF and slowing CKD progression. In this study, we demonstrated the dose-dependent attenuation of RIF by Ootheca mantidis (SPX), a commonly prescribed TCM for CKD, in a mouse model of unilateral ureteral obstruction (UUO). RNA-sequencing analysis suggested that SPX treatment prominently downregulated apoptosis and inflammation-associated pathways, thereby inhibiting the fibrogenic signaling in the kidney. We further found that transplantation of fecal microbiota from SPX-treated mice conferred protection against renal injury and fibrosis through suppressing apoptosis in UUO mice, indicating that SPX ameliorated RIF via remodeling the gut microbiota and reducing apoptosis in the kidneys. Further functional exploration of the gut microbiota combined with fecal metabolomics revealed increased levels of some probiotics, including Akkermansia muciniphila (A. muciniphila), and modulations in glutamine-related amino acid metabolism in UUO mice treated with SPX. Subsequent colonization of A. muciniphila and supplementation with glutamine effectively mitigated cell apoptosis and RIF in UUO mice. Collectively, these findings unveil a functionally A. muciniphila- and glutamine-involved gut–renal axis that contributes to the action of SPX, and provide important clue for the therapeutic potential of SPX, A. muciniphila, and glutamine in combatting RIF.

Analysis of the alleviating effect of modified Huangqi Chifeng decoction on rats with focal segmental glomerulosclerosis based on gut microbiota and fecal metabolomics.

To investigate the reno-protective effects of modified Huangqi Chifeng decoction (MHCD) on focal segmental glomerulosclerosis (FSGS) rats, and the underlying mechanisms of systemic regulation of gut microbiota and metabolite profiles. A rat FSGS model was established via unilateral nephrectomy plus doxorubicin injections. Rats were divided into sham, FSGS, and MHCD groups from which urine, blood, and histological tests were conducted. Fecal microbiotas were identified via 16S rRNA gene sequencing. Fecal metabolomics allowed for metabolic pathways analysis. Biochemical indices and pathological examination revealed that MHCD treatment improved the symptoms of FSGS, and corrected dysbiosis of gut microbiota, enriched the abundance of Bifidobacterium, Odoribacter, Christensella, Oscillospira, and reduced that of harmful bacteria such as Collinsella and Coprobacterilus at the genus level. Fecal metabolomic profiles revealed 152 different metabolites between the FSGS and sham groups, which are mainly enriched in signaling pathways like arachidonic acid, serotonergic synapse, and oxytocin. Besides, 93 differential metabolites between MHCD and FSGS groups were identified, which are mainly enriched in signaling pathways like steroid hormone biosynthesis, prostate cancer, and linoleic acid metabolism. Spearman's correlation analysis showed a correlation between differential fecal metabolites and enriched gut microbiota or serum biochemical parameters. MHCD may exert a reno-protective effect by regulating the gut microbiome and metabolite profiles in FSGS rats.

Untargeted Metabolomics of Feces Reveals Diagnostic and Prognostic Biomarkers for Active Tuberculosis and Latent Tuberculosis Infection: Potential Application for Precise and Non-Invasive Identification.

Distinguishing latent tuberculosis infection (LTBI) from active tuberculosis (ATB) is important to control the prevalence of tuberculosis; however, there is currently no effective method. The aim of this study was to discover specific metabolites through fecal untargeted metabolomics to discriminate ATB, individuals with LTBI, and healthy controls (HC) and to probe the metabolic perturbation associated with the progression of tuberculosis. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to comprehensively detect compounds in fecal samples from HC, LTBI, and ATB patients. Differential metabolites between the two groups were screened, and their underlying biological functions were explored. Candidate metabolites were selected and enrolled in LASSO regression analysis to construct diagnostic signatures for discriminating between HC, LTBI, and ATB. A receiver operating characteristic (ROC) curve was applied to evaluate diagnostic value. A nomogram was constructed to predict the risk of progression of LTBI. A total of 35 metabolites were found to exist differentially in HC, LTBI, and ATB, and eight biomarkers were selected. Three diagnostic signatures based on the eight biomarkers were constructed to distinguish between HC, LTBI, and ATB, demonstrating excellent discrimination performance in ROC analysis. A nomogram was successfully constructed to evaluate the risk of progression of LTBI to ATB. Moreover, 3,4-dimethylbenzoic acid has been shown to distinguish ATB patients with different responses to etiological tests. This study constructed diagnostic signatures based on fecal metabolic biomarkers that effectively discriminated HC, LTBI, and ATB, and established a predictive model to evaluate the risk of progression of LTBI to ATB. The results provide scientificevidence for establishing an accurate, sensitive, and noninvasive differential diagnosis scheme for tuberculosis.

Alterations of gut microbiota and metabolome in early chronic kidney disease patients complicated with hyperuricemia

ObjectThis study aims to investigate the changes in gut microbiota and metabolism of patients with chronic kidney disease (CKD) stage 1–2, as well as the potential impact of hyperuricemia (HUA) on these factors in CKD stage 1–2 patients. MethodsIn this study, fecal samples were collected from CKD stage 1–2 without HUA patients (CKD-N group), CKD stage 1–2 with HUA patients (CKD-H group), and healthy people controls (HCs group). The samples were then subjected to the microbiome (16S rRNA gene sequencing) and metabolome (liquid chromatography-tandem mass spectrometry) analyses. The multi-omics datasets were analyzed individually and integrated for combined analysis using various bioinformatics approaches. ResultsGut microbial dysbiosis was found in CKD-N and CKD-H patients. At the phylum level, compared to HCs group, Bacteroidetes decreased but Proteobacteria increased in CKD-H group significantly. Fusobacteria in CKD-N group was significantly lower than HCs group. At genus level, [Eubacterium]_ventriosum_group, Fusobacterium, Agathobacter, Parabacteroides, and Roseburia significantly changed in CKD groups. [Ruminococcus]_gnavus_group was significantly lower in CKD-H group than CKD-N group. Moreover, the fecal metabolome of CKD-N and CKD-H altered significantly. d-glutamine and d-glutamate metabolism, arginine and proline metabolism, histidine metabolism, and lysine biosynthesis were down-regulated in the CKD-N group. Phenylalanine metabolism, arginine and proline metabolism, purine metabolism, and beta-alanine metabolism were up-regulated in the CKD-H group. There was a significant difference between the two CKD groups in phenylalanine metabolism. The abundance change of [Ruminococcus]_gnavus_group, [Eubacterium]_ventriosum_group, UCG-002, Alistipes, and Bifidobacterium had a close correlation with differential metabolites. ConclusionThe gut microbiota and metabolic status undergo significant changes in CKD patients compared to healthy people. Additionally, HUA has been found to impact the gut microbiota of CKD patients, as well as their metabolism. The close association between gut microbiota and metabolites suggests that the former plays a crucial role in metabolism.

Gut microbial carbohydrate metabolism contributes to insulin resistance

Insulin resistance is the primary pathophysiology underlying metabolic syndrome and type 2 diabetes1,2. Previous metagenomic studies have described the characteristics of gut microbiota and their roles in metabolizing major nutrients in insulin resistance3–9. In particular, carbohydrate metabolism of commensals has been proposed to contribute up to 10% of the host’s overall energy extraction10, thereby playing a role in the pathogenesis of obesity and prediabetes3,4,6. Nevertheless, the underlying mechanism remains unclear. Here we investigate this relationship using a comprehensive multi-omics strategy in humans. We combine unbiased faecal metabolomics with metagenomics, host metabolomics and transcriptomics data to profile the involvement of the microbiome in insulin resistance. These data reveal that faecal carbohydrates, particularly host-accessible monosaccharides, are increased in individuals with insulin resistance and are associated with microbial carbohydrate metabolisms and host inflammatory cytokines. We identify gut bacteria associated with insulin resistance and insulin sensitivity that show a distinct pattern of carbohydrate metabolism, and demonstrate that insulin-sensitivity-associated bacteria ameliorate host phenotypes of insulin resistance in a mouse model. Our study, which provides a comprehensive view of the host–microorganism relationships in insulin resistance, reveals the impact of carbohydrate metabolism by microbiota, suggesting a potential therapeutic target for ameliorating insulin resistance.

Effects of a Very-Low-Calorie Ketogenic Diet on the Fecal and Urinary Volatilome in an Obese Patient Cohort: A Preliminary Investigation.

Several recent studies deepened the strong connection between gut microbiota and obesity. The effectiveness of the very-low-calorie ketogenic diet (VLCKD) has been measured in terms of positive impact on the host homeostasis, but little is known of the modification exerted on the intestinal metabolome. To inspect this complex relationship, we analyzed both fecal and urinary metabolome in terms of volatile organic compounds (VOCs) by the GC-MS method in 25 obese patients that were under VLCKD for eight weeks. Partial least square discriminant analysis evidenced specific urinary and fecal metabolites whose profile can be considered a signature of a partial restore toward the host eubiosis. Specifically, among various keystone VOCs, the decreased concentration of four statistically significant fecal esters (i.e., propanoic acid pentyl ester, butanoic acid hexyl ester, butanoic acid pentyl ester, and pentanoic acid butyl ester) supports the positive effect of VLCKD treatment. Our pilot study results suggest a potential positive effect of VLCKD intervention affecting fecal and urinary volatilome profiles from obese patients. Meta-omics techniques including the study of genes and transcripts will help in developing new interventions useful in preventing or treating obesity and its associated health problems.

Intestinal acetic acid regulates the synthesis of sex pheromones in captive giant pandas.

As a typical solitary animal, adult giant pandas rely on chemical signals (sex pheromones) to transmit reproductive information during oestrous. Although researchers have confirmed that the gut microbiota is related to the emission and reception of sex pheromones, there is no clear correlation between the gut microbes and the synthesis of sex pheromone of giant pandas, that is, which gut microbes and microbial metabolites are participate in the synthesis of giant panda's sex pheromone. As a mirror of gut microbiota, fecal microbiota can reflect the composition of gut microbiota and its interaction with host to some extent. The purpose of this study is to explore how the gut microbes affect the synthesis of sex pheromones in captive giant pandas by combining analysis of the fecal microbiome and metabolomics. The results of correlation and microbial function analysis show that intestinal microorganisms such as Veillonellaceae and Lactobacillilaceae are associated with the synthesis of short chain fatty acid (acetic acid) and volatile ester metabolites, such as 1-butanol, 3-methyl, acetate, acetic acid, hexyl ester and 3-hexen-1-ol, acetate, (Z). In summary, based on this study, we believe that volatile metabolites such as fecal acetate participate in the process of mate preference of captive giant pandas and affect their expression of natural mating behavior. The possible mechanism is that the gut microbes can promote the synthesis of key chemical signaling substances in perianal glands through mediated intermediate fecal metabolites, thus affecting the normal information exchange between giant pandas individuals. The results of this study have greatly enriched our understanding of gut microbes regulating the synthesis of sex pheromones in giant pandas.

Investigating the antidepressant effect of Ziyan green tea on chronic unpredictable mild stress mice through fecal metabolomics.

Some studies have shown the effectiveness of tea in reducing depression. Gut flora dysfunction is strongly associated with depression. The mechanism by which Ziyan green tea ameliorates depression is not clear. In this study, we examined the impact of Ziyan green tea on mice exhibiting symptoms similar to depression. We specifically focused on the role of intestinal flora and its metabolites. We first established a chronic unpredictable mild stress (CUMS) mouse model to induce depressive symptoms and conducted behavioural tests, biochemical tests, and pathological tissue analysis. We also investigated gut microbiota changes by 16S rRNA sequencing and measured faecal metabolites in mice using UHPLC-MS/MS. The results showed that Ziyan green tea intervention improved depression-like behaviour, neurobiochemical factors, and reduced levels of pro-inflammatory factors in CUMS mice. Spearman's correlation analysis showed that different microbial communities (Corynebacterium, Faecalibaculum, Enterorhabdus, Desulfovibrio) correlation with differential metabolites (Cholic acid, Deoxycholic acid, etc.) and depression-related biochemical indicators (5-HT, DA, BDNF, IL-6, and TNF-α). In conclusion, our findings suggest that both low and high-dose interventions of Ziyan green tea have positive preventive effects on CUMS mice without dose dependence, partly because they mainly affect intestinal Purine Metabolism, Bile Acid Biosynthesis and Cysteine Metabolism in CUMS mice, thus stimulating brain 5-HT, DA and BDNF, and decreasing the inflammatory factors IL-6, TNF-α, activate the composition of intestinal flora, improve the intestinal flora environment and thus promote the production of intestinal metabolites, which can be used for depression treatment. It is suggested that Ziyan green tea may achieve an antidepressant effect through the gut-microbiota-brain axis.

Modulatory Effects of Co-Fermented Pu-erh Tea with Aqueous Corn Silk Extract on Gut Microbes and Fecal Metabolites in Mice Fed High-Fat Diet.

Pu-erh tea is recognized for its weight loss effects, but its potential association with gut microbiota and metabolites remains unclear. This research explored the alterations in gut flora and metabolite composition upon treatment with a co-fermented Pu-erh tea with an aqueous corn silk extract (CPC) in obese mice by employing integrated 16S ribosomal RNA gene sequencing and untargeted metabolomics processes. For 8 weeks, mice were fed control, high-fat, and high-fat diets which included a 46 mg/mL CPC extract. The CPC extract the alleviated high-fat diet (HFD), it stimulated systemic chronic inflammation, and it reduced the body weight, daily energy consumption, and adipose tissue weight of the mice. It also modified the gut microbiota composition and modulated the Lactobacillus, Bifidobacterium, Allobaculum, Turicibacter, and Rikenella genera. Fecal metabolomics analysis revealed that the CPC extract influenced the caffeine, cysteine, methionine, tryptophan, biotin metabolism pathways, primary bile acid, and steroid biosynthesis. This research revealed that the CPC extract could inhibit HFD-stimulated abnormal weight gain and adipose tissue accumulation in mice, and modulate mice gut microbiota composition and multiple metabolic pathways.

Dioscoreae Rhizoma starch improves chronic diarrhea by regulating the gut microbiotas and fecal metabolome in rats.

Chinese yam (Dioscorea opposite Thunb.) has been used as food and medicine to treat diarrhea for thousands of years. This article aimed to elucidate the potential mechanism of Dioscoreae Rhizoma starch in alleviating chronic diarrhea induced by rhubarb based on gut microbiotas and fecal metabolome. The administration of the Dioscoreae Rhizoma aqueous extracts, crude polysaccharides, and starch could improve diarrhea and alleviate intestinal injury in chronic diarrhea rats. The Dioscoreae Rhizoma starch displayed the most apparent effect on regulating intestinal microbiotas by increasing the abundance and diversity of microbiotas. At the genus level, there were 17 changed intestinal microbiotas in model rats, and the treatment with Dioscoreae Rhizoma starch regulated 11 microbiotas. Metabolomics analysis revealed that Dioscoreae Rhizoma starch could regulate abnormal fecal metabolites to alleviate diarrhea, and these metabolites are involved in phenylalanine, tyrosine, and tryptophan biosynthesis; tyrosine metabolism; vitamin B6 metabolism; and purine metabolism. This study will contribute to the further research and development of Dioscoreae Rhizoma starch.

Epstein Barr virus infection in tree shrews alters the composition of gut microbiota and metabolome profile

BackgroundEpstein-Barr virus (EBV) infection is a major global threat; its manifestations range from the absence of symptoms to multiorgan malignancies and various gastrointestinal diseases. Analyzing the composition and metabolomic profile of gut microbiota during acute EBV infection might be instrumental in understanding and controlling EBV.MethodsSix tree shrews were inoculated with EBV by intravenous injection. Blood was collected at regular intervals thereafter from the femoral vein to detect EBV and inflammatory biomarker. At the same time, tree shrew faeces were collected for 16 S rRNA gene sequencing and Non-targeted metabolomics analysis.Results16 S rRNA gene characterization along with β diversity analysis exhibited remarkable alterations in gut microflora structure with a peak at 7 days post-infection(dpi). Some alterations in the relative richness of bacterial taxon were linked to infectious indicators. Of note, Butyricicoccus relative richness was positively linked to EBV presence in the blood and plasma, the opposite correlation was seen with Variovorax and Paramuribaculum. Non-targeted metabolomics indicated the fecal metabolome profile altered during EBV infection, particularly 7 dpi. The relative abundance of geranic acid and undecylenic acid in stool samples was positively linked to systemic inflammatory biomarkers, and an inverse relationship was reported with the estrone glucuronide, linoleic acid, protoporphyrin IX and tyramine.ConclusionCollectively, EBV infection in this model correlated with changes in the composition and metabolome profile of the gut microbiota.

Faecal Bacteriome and Metabolome Profiles Associated with Decreased Mucosal Inflammatory Activity Upon Anti-TNF Therapy in Paediatric Crohn's Disease.

Treatment with anti-tumour necrosis factor α antibodies [anti-TNF] changes the dysbiotic faecal bacteriome in Crohn's disease [CD]. However, it is not known whether these changes are due to decreasing mucosal inflammatory activity or whether similar bacteriome reactions might be observed in gut-healthy subjects. Therefore, we explored changes in the faecal bacteriome and metabolome upon anti-TNF administration [and therapeutic response] in children with CD and contrasted those to anti-TNF-treated children with juvenile idiopathic arthritis [JIA]. Faecal samples collected longitudinally before and during anti-TNF therapy were analysed with regard to the bacteriome by massively parallel sequencing of the 16S rDNA [V4 region] and the faecal metabolome by 1H nuclear magnetic resonance imaging. The response to treatment by mucosal healing was assessed by the MINI index at 3 months after the treatment started. We also tested several representative gut bacterial strains for in vitro growth inhibition by infliximab. We analysed 530 stool samples from 121 children [CD 54, JIA 18, healthy 49]. Bacterial community composition changed on anti-TNF in CD: three members of the class Clostridia increased on anti-TNF, whereas the class Bacteroidia decreased. Among faecal metabolites, glucose and glycerol increased, whereas isoleucine and uracil decreased. Some of these changes differed by treatment response [mucosal healing] after anti-TNF. No significant changes in the bacteriome or metabolome were noted upon anti-TNF in JIA. Bacterial growth was not affected by infliximab in a disc diffusion test. Our findings suggest that gut mucosal healing is responsible for the bacteriome and metabolome changes observed in CD, rather than any general effect of anti-TNF.

Long-term effects on liver metabolism induced by ceftriaxone sodium pretreatment

Ceftriaxone is an emerging contaminant due to its potential harm, while its effects on liver are still need to be clarified. In this study, we first pretreated the 8-week-old C57BL/6J mice with high dose ceftriaxone sodium (Cef, 400 mg/mL, 0.2 mL per dose) for 8 days to prepare a gut dysbiosis model, then treated with normal feed for a two-month recovery period, and applied non-targeted metabolomics (including lipidomics) to investigate the variations of fecal and liver metabolome, and coupled with targeted determination of fecal short-chain fatty acids (SCFAs) and bile acids (BAs). Lastly, the correlations and mediation analysis between the liver metabolism and gut metabolism/microbes were carried, and the potential mechanisms of the mal-effects on gut-liver axis induced by Cef pretreatment were accordingly discussed. Compared to the control group, Cef pretreatment reduced the rate of weight gain and hepatosomatic index, induced bile duct epithelial cells proliferated around the central vein and appearance of binucleated hepatocytes, decreased the ratio of total branching chains amino acids (BCAAs) to total aromatic amino acids (AAAs) in liver metabolome. In fecal metabolome, the total fecal SCFAs and BAs did not change significantly while butyric acid decreased and the primary BAs increased after Cef pretreatment. Correlation and mediation analysis revealed one potential mechanism that Cef may first change the intestinal microbiota (such as destroying its normal structure, reducing its abundance and the stability of the microbial network or certain microbe abundance like Alistipes), and then change the intestinal metabolism (such as acetate, caproate, propionate), leading to liver metabolic disorder (such as spermidine, inosine, cinnamaldehyde). This study proved the possibility of Cef-induced liver damage, displayed the overall metabolic profile of the liver following Cef pretreatment and provided a theoretical framework for further research into the mechanism of Cef-induced liver damage.