Fecal Metabolites Research Articles

Fecal microbiota and metabolites in the pathogenesis and precision medicine for inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, and its pathogenesis is believed to be associated with an imbalance between commensal organisms and the intestinal immune system. This imbalance is significantly influenced by the intestinal microbiota and metabolites and plays a critical role in maintaining intestinal mucosal homeostasis. However, disturbances in the intestinal microbiota cause dysregulated immune responses and consequently induce intestinal inflammation. Recent studies have illustrated the roles of the intestinal microbiota in the pathogenesis of IBD and underscored the potential of precision diagnosis and therapy. This work summarises recent progress in this field and particularly focuses on the application of the intestinal microbiota and metabolites in the precision diagnosis, prognosis assessment, treatment effectiveness evaluation, and therapeutic management of IBD.

Should Pregnant Women Consume Probiotics to Combat Endocrine-Disrupting Chemical-Induced Health Risks to Their Unborn Offspring?

Endocrine-disrupting chemicals (EDCs) have become so pervasive in our environment and daily lives that it is impossible to avoid contact with such compounds, including pregnant women seeking to minimize exposures to themselves and their unborn children. Developmental exposure of humans and rodent models to bisphenol A (BPA) and other EDCs is linked to increased anxiogenic behaviors, learning and memory deficits, and decreased socio-sexual behaviors. Prenatal exposure to BPA and other EDCs leads to longstanding and harmful effects on gut microbiota with reductions in beneficial bacteria, i.e., gut dysbiosis, and such microbial changes are linked to host changes in fecal metabolites, including those involved in carbohydrate metabolism and synthesis, and neurobehavioral alterations in adulthood, in particular, social and cognitive deficits. Gut dysbiosis is increasingly being recognized as a key driver of a myriad of diseases, ranging from metabolic, cardiovascular, reproductive, and neurobehavioral disorders via the gut-microbiome-brain axis. Thus, EDCs might induce indirect effects on physical and mental health by acting as microbiome-disrupting chemicals. Findings raise the important question as to whether pregnant women should consume a probiotic supplement to mitigate pernicious effects of EDCs, especially BPA, on themselves and their unborn offspring. Current studies investigating the effects of maternal probiotic supplementation on pregnant women's health and that of their unborn offspring will be reviewed. Data will inform on the potential application of probiotic supplementation to reverse harmful effects of EDCs, especially BPA, in pregnant women unwittingly exposed to these compounds and striving to give their offspring the best start in life.

The brain-protective mechanism of fecal microbiota transplantation from young donor mice in the natural aging process via exosome, gut microbiota, and metabolomics analyses

The natural aging process is accompanied by changes in exosomes, gut microbiota, and metabolites. This study aimed to reveal the anti-aging effect and mechanisms of fecal microbiota transplantation (FMT) from young donors on the natural aging process in mice by analyzing exosomes, gut microbiota, and metabolomics. Aging-relevant telomeric length, oxidative stress indexes in brain tissue, and serum cytokine levels were measured. Flow analysis of T-regulatory (Treg), CD4+, and CD8+ cells was performed, and the expression levels of aging-related proteins were quantified. High-throughput sequencing technology was used to identify differentially expressed serum exosomal miRNAs. Fecal microbiota was tested by 16 S rDNA sequencing. Changes in fecal metabolites were analyzed by UPLC-Q-TOF/MS. The results indicated that the expression of mmu-miR-7010–5p, mmu-miR-376b-5p, mmu-miR-135a-5p, and mmu-miR-3100–5p by serum exosomes was down-regulated and the abundance of opportunistic bacteria (Turicibacter, Allobaculum, Morganella.) was decreased, whereas the levels of protective bacteria (Akkermansia, Muribaculaceae, Helicobacter.) were increased after FMT. Metabolic analysis identified 25 potential biomarkers. Correlation analysis between the gut microbiota and metabolites suggested that the relative abundance of protective bacteria was positively correlated with the levels of spermidine and S-adenosylmethionine. The study indicated that FMT corrected brain injury due to aging via lipid metabolism, the metabolism of cofactors and vitamins, and amino acid metabolism.

Signals from intestinal microbiota mediate the crosstalk between the lung-gut axis in an influenza infection mouse model.

Introduction: The influenza virus primarily targets the respiratory tract, yet both the respiratory and intestinal systems suffer damage during infection. The connection between lung and intestinal damage remains unclear. Our experiment employs 16S rRNA technology and Liquid Chromatography-Mass Spectrometry (LC-MS) to detect the impact of influenza virus infection on the fecal content and metabolites in mice. Additionally, it investigates the effect of influenza virus infection on intestinal damage and its underlying mechanisms through HE staining, Western blot, Q-PCR, and flow cytometry. Our study found that influenza virus infection caused significant damage to both the lungs and intestines, with the virus detected exclusively in the lungs. Antibiotic treatment worsened the severity of lung and intestinal damage. Moreover, mRNA levels of Toll-like receptor 7 (TLR7) and Interferon-b (IFN-b) significantly increased in the lungs post-infection. Analysis of intestinal microbiota revealed notable shifts in composition after influenza infection, including increased Enterobacteriaceae and decreased Lactobacillaceae. Conversely, antibiotic treatment reduced microbial diversity, notably affecting Firmicutes, Proteobacteria, and Bacteroidetes. Metabolomics showed altered amino acid metabolism pathways due to influenza infection and antibiotics. Abnormal expression of indoleamine 2,3-dioxygenase 1 (IDO1) in the colon disrupted the balance between helper T17 cells (Th17) and regulatory T cells (Treg cells) in the intestine. Mice infected with the influenza virus and supplemented with tryptophan and Lactobacillus showed reduced lung and intestinal damage, decreased Enterobacteriaceae levels in the intestine, and decreased IDO1 activity. Overall, influenza infection caused damage to lung and intestinal tissues, disrupted intestinal microbiota and metabolites, and affected Th17/Treg balance. Antibiotic treatment exacerbated these effects. Supplementation with tryptophan and Lactobacillus improved lung and intestinal health, highlighting a new understanding of the lung-intestine connection in influenza-induced intestinal disease.

Gut microbiota and metabolic changes in children with idiopathic short stature

BackgroundIdiopathic short stature (ISS) is characterized by short stature with unknown causes. Recent studies showed different gut microbiota flora and reduced fecal short-chain fatty acids in ISS children. However, the roles of the microbiome and metabolites in the pathogenesis of ISS remains largely unknown.MethodsWe recruited 51 Chinese subjects, comprising 26 ISS children and 25 normal-height control individuals. Untargeted metabolomics was performed to explore the fecal metabolic profiles between groups. A shotgun metagenomic sequencing approach was used to investigate the microbiome at the strains level. Mediation analyses were done to reveal correlations between the height standard deviation (SD) value, the gut microbiome and metabolites.ResultsWe detected marked differences in the composition of fecal metabolites in the ISS group, particularly a significant increase in erucic acid and a decrease in spermidine, adenosine and L-5-Hydroxytryptophan, when compared to those of controls. We further identified specific groups of bacterial strains to be associated with the different metabolic profile. Through mediation analysis, 50 linkages were established. KEGG pathway analysis of microbiota and metabolites indicated nutritional disturbances. 13 selected features were able to accurately distinguish the ISS children from the controls (AUC = 0.933 [95%CI, 79.9–100%]) by receiver operating characteristic (ROC) analysis.ConclusionOur study suggests that the microbiome and the microbial-derived metabolites play certain roles in children’s growth. These findings provide a new research direction for better understanding the mechanism(s) underlying ISS.

Shenling Baizhu Decoction treats ulcerative colitis of spleen-deficiency and dampness obstruction types by targeting ‘gut microbiota and galactose metabolism-bone marrow’ axis

Ethnopharmacological relevanceShenlin Baizhu Decoction (SLBZD), which comes from ‘Taiping Huimin Heji Ju Fang’, belongs to a classical prescription for treating spleen deficiency and dampness obstruction (SQDDS)-type ulcerative colitis (UC) in traditional Chinese medicine. However, the mechanism of SLBZD in treating UC with SQDDS remains unclear. Aim of the studyThis study aims to investigate the mechanism of SLBZD against SQDDS-type UC of based on the “gut microbiota and metabolism - bone marrow” axis to induce endogenous bone marrow mesenchymal stem cells (BMSCs) homing. Materials and methodsUltra-performance liquid chromatography-mass spectrometry was used to analysis of SLBZD qualitatively. The efficacy of SLBZD in SQDDS-type UC was evaluated based on the following indicators: the body weight, colon length, disease activity index (DAI) score, Haemotoxylin and Eosin (H&E) pathological sections, and intestinal permeability proteins (occluding and ZO-1). 16S rRNA gene sequencing and non-target metabolomics were performed to identify gut microbiota changes and its metabolites in feces, respectively. BMSCs in each group was collected, cultured, and analyzed. Optimal passaged BMSCs were injected by tail vein into UC rats of SQDDS types. BMSCs homing to the colonic mucosal tissue was observed by immunofluorescent. Finally, the repairing effect of BMSCs homing to the colonic mucosal tissue after SLBZD treatment was analyzed by transmission electron microscopy, qRT-PCR, and immunohistochemistry. ResultsSLBZD effectively improved the colonic length and the body weight, reduced DAI and H&E scores, and increased the expression of the intestinal permeability proteins, including occluding and ZO-1, to treat SQDDS-type UC. After SLBZD treatment, the α-diversity and β-diversity of the gut microbiota were improved. The differential microbiota was screened as Aeromonadaceae, Lactobacillaceae, and Clostridiaceae at the family level, and Aeromonas, Lactobacillus, Clostridium_sensu_stricto_1 at the genus level. Meanwhile, the main metabolic pathway was the galactose metabolism pathway. SLBZD treatment timely corrected the aberrant levels of β-galactose in peripheral blood and bone marrow, senescence-associate-β-galactosidase in BMSCs, and galactose kinase-2, galactose mutase, and galactosidase beta-1 in peripheral blood to further elevate the expression levels of senescence-associated (SA) proteins (p16, p53, p21, and p27) in BMSCs. The Spearman's correlation analysis demonstrated the relationship between microbiota and metabolism, and the relationship between the galactose metabolism pathway and SA proteins. After BMSCs in each group injection via the tail vein, the pharmacodynamic effects were consistent with those of SLBZD in SQDDS-type UC rats. Furthermore, BMSCs have been homing to colonic mucosal tissue. BMSCs from the SLBZD treatment group had stronger restorative effects on intestinal permeability function due to increasing protein and mRNA expressions of occludin and ZO-1, and decreasing the proteins and mRNA expressions of SDF-1 and CXCR4 in colon. ConclusionsSLBZD alleviated the damaged structure of gut microbiota and regulated their metabolism, specifically the galactose metabolism, to treat UC of SDDOS types. SLBZD treatment promotes endogenous BMSCs homing to colonic mucosal tissue to repaire the intestinal permeability. The current exploration revealed an underlying mechanism wherein SLBZD activates endogenous BMSCs by targeting ‘the gut microbiota and its metabolism-bone marrow’ axis and repairs colonic mucosal damage to treat SDDOS-type UC.

Fructus Jujubae cooperated with water-expelling members in Shizao decoction alleviated intestinal injury and malignant ascites by modulating gut microbiota and metabolic homeostasis

BackgroundShizao decoction (SZD) consisted of Euphorbia kansui (EK), Euphorbia pekinensis (EP), Daphne genkwa (DG), and Fructus Jujubae (FJ) is a classic Chinese herbal medicine formula for treating malignant ascites, which is closely related to the modulation of gut microbiota by our previous study. For water-expelling members (WEM) including EK, EP, and DG may have side effects on the intestine, FJ is employed for detoxification and effectivity enhancement of WEM. However, the underlying mechanism for the compatibility of WEM and FJ is still unknown. PurposeTo investigate the effect of the compatibility of WEM with FJ in SZD on malignant ascites and elucidate the potential mechanism from the perspective of the modulation of gut microbiota and related metabolic function. MethodsQualitative and quantitative evaluation of main components was conducted for comprehensive characterization of SZD and WEM. The effect of WEM and SZD was compared on malignant ascites effusion (MAE) rats. The intestinal injury was evaluated by HE staining and oxidative damage. Ascites weight, urine amount, fecal water content, the expression of aquaporins, and cytokines in ascites (IL-6, VEGF, and TNF-α) were measured to estimate the water-expelling activity. The intestinal flora was detected by 16S rDNA sequencing and the content of fecal short-chain fatty acids (SCFAs) was analyzed using gas chromatography-mass spectrometry. Pseudo-germ-free (PGF) and fecal bacteria transplantation animal experiments were subsequently employed to validate this finding. The fecal metabolomics and correlation analysis were finally conducted to explore the related metabolic changes. Results51 and 33 components were identified in SZD and WEM, respectively. Compared to WEM alone, the compatibility with FJ remarkably reduced intestinal oxidative damage in MAE rats. Ascites was also relieved by downregulating the expression of AQP3 in the colon and decreasing the levels of IL-6, TNF-α and VEGF in ascites. The diversity of gut microbiota was reversed with an increase in Lactobacillus and Clostridia_UCG-014 while a decrease in Colidextribacter. Under the PGF condition, compatibility of WEM with FJ failed to reduce intestinal injury and alleviate MA significantly, but this effect was further enhanced after FMT. 23 potential fecal metabolites were finally identified. Correlation analysis further showed that Lactobacillus and Clostridia_UCG-014 were positively correlated with SCFAs and l-tryptophan. Colidextribacter was negatively correlated with thymidine but positively correlated with ursodeoxycholic acid and deoxycholic acid. ConclusionFJ cooperated with WEM reduced intestinal injury and alleviated malignant ascites by modulating gut microbiota, short-chain fatty and tryptophan metabolism. These findings provide a scientific basis for the clinical application of FJ from SZD and the safe usage of SZD.

Gut microbiota and metabolites of cirrhotic portal hypertension: a novel target on the therapeutic regulation.

The regulatory role of gut microbiota and gut-derived metabolites through the gut-liver axis in the development of cirrhotic portal hypertension (PH) has received increasing attention. The review summarized a series of investigations on effects of metabolites derived from microbiota and medicines targeting microbiome including rifaximin, VSL#3, statins, propranolol, FXR agonists as well as drugs derived from bile acids (BAs) on PH progression. Patients with PH exhibit alterations in gut microbial richness and differential overall microbiota community, and several results clearly displayed the correlation of PH with enrichment of Veillonella dispar or depletion of Clostridiales, Peptostreptococcaceae, Alistipes putredinis, Roseburia faecis and Clostridium cluster IV. The gut-derived metabolites including hydrogen sulfide, tryptophan metabolites, butyric acid, secondary BAs and phenylacetic acid (PAA) participate in a range of pathophysiology process of PH through modulating intrahepatic vascular resistance and portal blood flow associated with the formation and progression of PH. Established and emerging drugs targeting on bacterial translocation and intestinal eubiosis are gradually identified as potential strategies for treatments of liver cirrhosis and PH by modulating intestinal inflammation, splanchnic arterial vasodilation and endothelial dysfunction. Future explorations should further characterize the alteration of the fecal microbiome and metabolite profiles in PH and elucidate the regulatory mechanism of the intestinal microbiome, gut-derived metabolites and gut microbiota targeted pharmaceutical treatments involved in PH.

Early and long-term responses of intestinal microbiota and metabolites to 131I treatment in differentiated thyroid cancer patients

BackgroundMultiple high doses of 131I therapy in patients with differentiated thyroid cancer (DTC) might disrupt the balance of gut microbiota and metabolites. This study aimed to investigate the alterations of intestinal bacteria and metabolism over two courses of 131I therapy, explore the interactions, and construct diagnostic models reflecting enteric microecology based on 131I therapy.MethodsA total of 81 patients were recruited for the first 131I therapy (131I-1st), among whom 16 received a second course (131I-2nd) after half a year. Fecal samples were collected 1 day before (Pre-131I-1st/2nd) and 3 days after (Post-131I-1st/2nd) 131I therapy for microbiome (16S rRNA gene sequencing) and metabolomic (LC–MS/MS) analyses.ResultsA total of six microbial genera and 11 fecal metabolites enriched in three pathways were identified to show significant differences between Pre-131I-1st and other groups throughout the two courses of 131I treatment. In the Post-131I-1st group, the beneficial bacteria Bifidobacterium, Lachnoclostridium, uncultured_bacterium_f_Lachnospiraceae, and Lachnospiraceae_UCG004 were abundant and the radiation-sensitive pathways of linoleic acid (LA), arachidonic acid, and tryptophan metabolism were inhibited compared with the Pre-131I-1st group. Compared with the Pre-131I-1st group, the Pre-131I-2nd group exhibited a reduced diversity of flora and differentially expressed metabolites, with a low abundance of beneficial bacteria and dysregulated radiation-sensitive pathways. However, less significant differences in microbiota and metabolites were found between the Pre/Post-131I-2nd groups compared with those between the Pre/Post-131I-1st groups. A complex co-occurrence was observed between 6 genera and 11 metabolites, with Lachnoclostridium, Lachnospiraceae_UCG004, Escherichia-Shigella, and LA-related metabolites contributing the most. Furthermore, combined diagnostic models of charactered bacteria and metabolites answered well in the early, long-term, and dose-dependent responses for 131I therapy.ConclusionsDifferent stages of 131I therapy exert various effects on gut microecology, which play an essential role in regulating radiotoxicity and predicting the therapeutic response.

Alteration of Fecal Microbiota, Fecal Metabolites, and Serum Metabolites in Dairy Cows with Pre-Retained Placenta.

Retained placenta (RP) affects lactation and fertility in dairy cows and causes economic losses to the dairy industry. Therefore, screening for early warning of this disease is important. This study used multi omics techniques to reveal the metabolic differences of dairy cows before RP onset and to find potential warning markers. Fecal samples and serum samples of 90 healthy Holstein cows were collected 7 days pre-calving; 10 healthy and 10 RP cows were enrolled according to normal expulsion of fetal membranes after calving. Fecal samples were subjected to 16S rRNA sequencing and untargeted metabolomics analysis, while plasma was analyzed using targeted metabolomics. Pathogenic bacteria levels increased in the intestines of cows with RP compared to those in healthy cows. Lipid metabolites constituted the largest proportion of differential metabolites between feces and plasma. Six potential warning markers for RP in cows were identified, including two fecal microbiomics markers (Oscillospiraceae UCG-005 and Escherichia-Shigella), one fecal untargeted metabolomics marker (N-acetylmuramic acid), and three plasma targeted metabolomics markers (glycylcholic acid-3 sulfate, 7-ketolithocholic acid, and 12-ketolithocholic acid). These biomarkers can predict RP occurrence in the early perinatal period. These results lay a theoretical foundation for early nutritional intervention and pathogenesis research in dairy cows.

Intestinal mycobiota dysbiosis associated inflammation activation in chronic schizophrenia

The microbiome–gut–brain axis is related to schizophrenia (SCZ). The role of intestinal mycobiota in SCZ has been under investigated. We present a half-year follow-up study involving 109 chronic SCZ patients and 77 healthy controls. Intestinal mycobiota was tested by internal transcribed spacer (ITS). Untargeted liquid chromatography-mass spectrometry (LC-MS) was used to measure fecal metabolites. Symptom severity was assessed using the Positive and Negative Syndrome Scale. Enterotype analysis showed that Candida-type patients exhibited severer positive symptoms and depression factors than Saccharomyces-type patients. Candida and its top species and operational taxonomic units (OTUs) were positively correlated with depression factors (all p=0.001). Fecal metabolites analysis showed that upregulated metabolites were associated with chronic inflammation (NF-κB pathway and T helper cell differentiation), downregulated metabolites were associated with glutamate metabolism, serotonergic and dopaminergic synapse. Procrustes analysis revealed significant correlation between intestinal mycobiota and fecal metabolites (M2=0.937, p<0.001). Metabolic module analysis showed that the top module, MEturquoise (associated with Th1 and Th2 cell differentiation), was negatively correlated with SCZ (r=-0.783, p<0.0001), positively correlated with Candida, Aspergillus, Trichosporon and Talaromyces (decreased in SCZ) and negatively correlated with Saccharomyces (increased in SCZ). We also found impairments of intestinal barrier in SCZ, characterized by increased in blood D-lactate (mucosa impairment marker) and decreased in blood mucin 2 (mucosal barrier protective protein). Serum levels of TNF-α was increased and showed stable high levels during treatment. This study suggests that mycobiota dysbiosis-related chronic inflammation and an impaired intestinal mucosal barrier are associated with chronic SCZ.

Treatment of Active Crohn's Disease With Exclusive Enteral Nutrition Diminishes the Immunostimulatory Potential of Fecal Microbial Products.

Exclusive enteral nutrition (EEN) is an effective treatment for active Crohn's disease (CD). This study explored the immunostimulatory potential of a cell-free fecal filtrate and related this with changes in the fecal microbiota and metabolites in children with active CD undertaking treatment with EEN. Production of tumor necrosis factor α (TNFα) from peripheral blood mononuclear cells was measured following their stimulation with cell-free fecal slurries from children with CD, before, during, and at completion of EEN. The metabolomic profile of the feces used was quantified using proton nuclear magnetic resonance and their microbiota composition with 16S ribosomal RNA sequencing. Following treatment with EEN, 8 (72%) of 11 patients demonstrated a reduction in fecal calprotectin (FC) >50% and were subsequently labeled FC responders. In this subgroup, TNFα production from peripheral blood mononuclear cells was reduced during EEN (P = .008) and reached levels like healthy control subjects. In parallel to these changes, the fecal concentrations of acetate, butyrate, propionate, choline, and uracil significantly decreased in FC responders, and p-cresol significantly increased. At EEN completion, TNFα production from peripheral blood mononuclear cells was positively correlated with butyrate (rho = 0.70; P = .016). Microbiota structure (β diversity) was influenced by EEN treatment, and a total of 28 microbial taxa changed significantly in fecal calprotectin responders. At EEN completion, TNFα production positively correlated with the abundance of fiber fermenters from Lachnospiraceae_UCG-004 and Faecalibacterium prausnitzii and negatively with Hungatella and Eisenbergiella tayi. This study offers proof-of concept data to suggest that the efficacy of EEN may result from modulation of diet-dependent microbes and their products that cause inflammation in patients with CD.

Evidence-Based Severity Assessment of Animal Models for Pancreatic Cancer.

Animal models are crucial to preclinical oncological research and drug development. Animal experiments must be performed in accordance with the 3R principles of replacement and reduction, if possible, and refinement where these procedures remain crucial. In addition, European Union legislations demand a continuous refinement approach, as well as pro- and retrospective severity assessment. In this study, an objective databased severity assessment was performed in murine models for pancreatic cancer induced by orthotopic, subcutaneous, or intravenous injection of Panc02 cells. Parameters such as body weight change, distress score, perianal temperature, mouse grimace scale, burrowing, nesting behavior, and the concentration of corticosterone in plasma and its metabolites in feces were monitored during tumor progression. The most important parameters were combined into a score and mapped against a reference data set by the Relative Severity Assessment procedure (RELSA) to obtain the maximum achieved severity for each animal (RELSAmax). This scoring revealed a significantly higher RELSAmax for the orthotopic model than for the subcutaneous and intravenous models. However, compared to animal models such as pancreatitis and bile duct ligation, the pancreatic cancer models are shown to be less severe. Data-based animal welfare assessment proved to be a valuable tool for comparing the severity of differently induced cancer models.

Anti-inflammation mechanisms of a homogeneous polysaccharide from Phyllanthus emblica L. on DSS induced colitis mice via the gut microbiota and metabolites alteration

Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation.

Impacts of a highly pathogenic ovine Eimeria ovinoidalis on the growth of Hu lambs

The apicomplexan Eimeria ovinoidalis is distributed worldwide. It can cause clinical coccidiosis, which is one of the most pathogenic species in sheep, reducing growth rates and resulting in significant economic losses in the industry. Its principal clinical sign is profuse diarrhoea in young animals. In this study, we established a model of E. ovinoidalis infection in lambs to understand its pathogenicity and evaluate the gut microbiota and fecal metabolite profiles. Specifically, we observed a significant shift in the abundance of bacteria and disrupted metabolism in lambs. Especially during the peak period of excrete oocysts, it promoted the reproduction of some harmful bacteria in Proteobacteria and Actinobacteriota, and reduced the abundance of beneficial bacteria such as Lachnospiraceae and Rikenellaceae. In the later stage of the patent period, the abundance of harmful bacteria in the intestine decreased, the abundance of beneficial bacteria which could produce anti-inflammatory substances began to increase, and the abundance and diversity of intestinal flora also tended to parallel with the control group. Coccidia infection could lead to the increase of differential metabolites and metabolic pathways between infected and control group, but the difference decreased with time. During the peak period of excrete oocysts, although the antimicrobial metabolites such as Lividamine were up-regulated, the excess of these metabolites could still induce the production of endotoxin, while Butanoic acid and other anti-inflammatory metabolites decreased significantly. A metabolomics analysis showed that E. ovinoidalis infection altered metabolites and metabolic pathways, with biosynthesis of unsaturated fatty acids, Teichoic acid biosynthesis and Butanoate metabolism as the major disrupted metabolic pathways. Details of the gut microbiota and the metabolome after infection with E. ovinoidalis may aid in the discovery of specific diagnostic markers and help us understand the changes in parasite metabolic pathways.

Flexible males, reactive females: faecal glucocorticoid metabolites indicate increased stress in the colonist population, damping with time in males but not in females.

Individuals colonizing new areas at expanding ranges encounter numerous and unpredictable stressors. Exposure to unfamiliar environments suggests that colonists would differ in stress levels from residents living in familiar conditions. Few empirical studies tested this hypothesis and produced mixed results, and the role of stress regulation in colonization remains unclear. Studies relating stress levels to colonization mainly use a geographical analysis comparing established colonist populations with source populations. We used faecal glucocorticoid metabolites (FGMs) to assess both spatial and temporal dynamics of stress levels in an expanding population of midday gerbils (Meriones meridianus). We demonstrated that adult males and females had higher FGM levels in newly emerged colonies, compared with the source population, but differed in the pattern of FGM dynamics post-foundation. In males, FGM levels sharply decreased in the second year after colony establishment. In females, FGM levels did not change with time and remained high despite the decreasing environmental unpredictability, exhibiting among-individual variation. Increased stress levels of colonist males damping with time post-colonization suggest they are flexible in responding to immediate changes in environmental uncertainty. On the contrary, high and stable over generations stress levels uncoupled from the changes in the environmental uncertainty in female colonists imply that they carry a relatively constant phenotype associated with the reactive coping strategy favouring colonization. We link sex differences in consistency and plasticity in stress regulation during colonization to the sex-specific life-history strategies.

Fecal Microbiota and Metabolites Predict Metabolic Health Features Across Various Dietary Patterns

Fecal Microbiota and Metabolites Predict Metabolic Health Features Across Various Dietary Patterns

Transcriptomic and Metabolomic Correlates of Increased Colonic Permeability in Postinfection Irritable Bowel Syndrome

Background and aimPost-infection irritable bowel syndrome (PI-IBS) is well-known epidemiologically; however, its physiological and molecular characteristics are not well studied. We aimed to determine the physiological phenotypes, colonic transcriptome, fecal microbiome, and metabolome in PI-IBS. MethodsFifty-one Rome III Campylobacter PI-IBS patients and 39 healthy volunteers (HV) were enrolled. Participants completed questionnaires, in vivo intestinal permeability, gastrointestinal transit, and rectal sensation. Fecal samples were collected for shotgun metagenomics, untargeted metabolomics, and sigmoid colonic biopsies for bulk RNAseq. Differential gene expression, differences in microbiota composition and metabolite abundance were determined. Gene and metabolite clusters were identified via weighted gene correlation network analysis and correlations with clinical and physiological parameters determined. ResultsPI-IBS (59% F, 46±2 yrs.) and HV (64% F, 42±2 yrs.) demographics were comparable. Mean IBS-symptom severity score was 227; 94% were non-constipation. 2-24h lactulose excretion was increased in PI-IBS, suggesting increased colonic permeability (4.4±0.5 mg vs. 2.6±0.3 mg, p=0.01). Colonic transit and sensory thresholds were similar between the two groups. Overall, expression of 2036 mucosal genes and 223 fecal metabolites were different, with changes more prominent in females. Fecal N-acetylputrescine was increased in PI-IBS and associated with colonic permeability, worse diarrhea, and negatively correlated with abundance of Collinsella aerofaciens. Histamine and N-acetyl histamine positively associated with 2-24 hr lactulose excretion. Eight weighted gene coexpression modules significantly correlated with phenotypes (sex, stool frequency, colonic permeability, transit). ConclusionsCampylobacter PI-IBS patients demonstrate higher colonic permeability which associated with changes in polyamine and histamine metabolites. Female patients demonstrated greater molecular changes.

Characteristics of Gut Microbiota and Fecal Metabolites in Patients with Colorectal Cancer-Associated Iron Deficiency Anemia.

Patients with colorectal cancer (CRC) have a high prevalence of iron deficiency anemia (IDA), and the gut microbiota is closely related to iron metabolism. We performed metagenomic and metabolomic analyses of stool samples from 558 eligible samples, including IDA CRC patients (IDA, n = 69), non-anemia CRC patients (Non-Anemia, n = 245), and healthy controls (CTRL, n = 244), to explore the dynamically altered gut microbes and their metabolites. Compared with the CTRL group, fecal bacteria in both the IDA group and the Non-Anemia group showed a decrease in alpha diversity and changes in microbial communities. Flavonifractor plautii (F. plautii) increases progressively from CTRL to Non-Anemia to IDA, accompanied by decreased trimethoxyflavanone and a downregulated KO gene, megDIII. In the Non-Anemia group, Parabacteroides showed a specifically elevated abundance positively correlated with enriched 1,25-dihydroxyvitamin D3. The intricate correlations among gut microbiota, metabolites, and KO genes were uncovered and highlighted, implicating an aberrant iron metabolism vulnerable to chronic inflammation during the deterioration of the anemic condition. Furthermore, the amount of F. plautii in feces achieved independent and effective prediction performance for the poor outcome of CRC. Perturbed host-microbe interplays represent a novel prospect for explaining the pathogenesis of CRC-associated IDA. The fecal microbial features also reflect the associations between IDA and elevated CRC recurrence risk.

Investigating the biological relevance of measuring gastrointestinal cortisol metabolite levels to assess stress responses in Atlantic salmon (Salmo salar L.) after an acute stress

Monitoring stress levels of farmed Atlantic salmon (Salmo salar) is important to ensure fish welfare and optimize farm operations. Feces could be a promising matrix for assessing stress responses in fish, based on their properties of low-invasive sampling and allowing repeated sampling over time. Meanwhile, elevated levels of cortisol metabolites (CMs) in feces indicate the increases in plasma cortisol levels (PLA) after exposure to acute stress. However, the dynamics of fecal CMs following acute stress in Atlantic salmon remain unclear. In this study, a confinement stress involving chasing and crowding was conducted to investigate the responses of gastrointestinal CMs to an acute stressor in Atlantic salmon. The post-smolts, with an average weight of 155.21 g, were sampled before and at 30 min, 1.5, 6, 12, 18, 24, 36, and 48 h after the onset of stress. Blood and gastrointestinal contents from the stomach, proximal intestine, and distal intestine of each fish were collected and subsequently analyzed, using competitive enzyme-linked immunosorbent assay (ELISA). The results demonstrated that the pre-stress level of PLA was low (4.28 ± 6.13 ng/ml) and reached a peak within 30 min following stress. The levels of CMs in gastrointestinal contents from stomach (SCMs), proximal intestine (PCMs), and distal intestine (DCMs) in pre-stress group were 0.82 ± 0.50, 18.31 ± 6.14 and 16.04 ± 6.69 ng/g, respectively. Gastrointestinal CMs increased significantly within 30 min and the peak levels of SCMs (3.51 ± 3.75 ng/g), PCMs (68.19 ± 23.71 ng/g) and DCMs (65.67 ± 23.37 ng/g) were found at 1.5 h post-stress. The significant increases in PCMs and DCMs post-stress validate the biological relevance of measuring intestinal CMs for assessing acute stress responses in Atlantic salmon. No significant difference was noted between PCMs and DCMs across all samples, suggesting that intestinal contents can serve as a suitable matrix compared with feces when measuring the responses of CMs to acute stress. The time lag between the peak of PLA levels and their reflection in the intestinal contents exceeded 1 h, indicating that using intestinal contents as a matrix to assess stress levels in fish can extend and delay the sampling window. This study highlights valuable guidance for determining the optimal times to utilize intestinal contents for measuring stress responses, providing further insights into the dynamics of fecal CM following acute stress.