Fecal Metabolites Research Articles

Temporal and Spatial Influences on Fawn Summer Survival in Pronghorn Populations: Management Implications from Noninvasive Monitoring.

Monitoring vital rates allows managers to estimate trends in growth rates of ungulate populations. However, connecting the influence of nutrition on ungulate demography is challenging. Noninvasive sampling offers a low-cost, low-effort alternative for measuring nutritional indices, allowing for an increased understanding of the mechanistic relationships between environmental factors, nutrition, and specific population vital rates. We examined the temporal influence of intrinsic and extrinsic factors on pronghorn (Antilocapra americana) fawn recruitment. We collected fresh fecal samples from adult female pronghorn in five subpopulations spanning three sampling periods associated with critical maternal life-history stages (late gestation, early lactation, breeding season) for 2 years to investigate both intra- and interannual influences. Intrinsic factors were fecal glucocorticoid metabolites (FGMs), nutritional indices (fecal nitrogen (FN) and 2,6-diaminopimelic acid (DAPA)), and dietary composition (protein intake of forbs, graminoids, legumes, other, shrubs), while the extrinsic factor was vegetative greenness (normalized difference vegetation index (NDVI)). We found variations in DAPA, protein intake of forbs, variation in forb protein intake, and protein intake of legumes during late gestation positively influenced fawn recruitment. Fecal nitrogen during early lactation showed the strongest positive influence on the recruitment of any measured parameter. Finally, breeding season NDVI and the variation in DAPA values positively influenced the subsequent year's fawn recruitment. Our longitudinal study enabled us to investigate which parameter was most important to specific periods of fawn development and recruitment. We combined the results across five subpopulations, but interpretation and subsequent management decisions should be made at the subpopulation level such that pronghorn subpopulations with low recruitment can be positively influenced by increasing nitrogen on the landscape available to adult females during the early lactation period. As the use of noninvasive monitoring methods continues to expand, we believe our methodologies and results can be broadly applied to other ungulate monitoring programs.

The prevention effect of Limosilactobacillus reuteri on acute kidney injury by regulating gut microbiota.

Acute kidney injury (AKI) has considerably high morbidity and mortality but we do not have proper treatment for it. There is an urgent need to develop new prevention or treatment methods. Gut microbiota has a close connection with renal diseases and has become the new therapy target for AKI. In this study, we found the oral administration of the probiotic Limosilactobacillus reuteri had a prevention effect on the AKI induced by lipopolysaccharide (LPS). It reduced serum concentration of creatinine and urea nitrogen and protected the renal cells from necrosis and apoptosis. Meanwhile, L. reuteri improved the gut barrier function, which is destroyed in AKI, and modulated the gut microbiota and relevant metabolites. Compared with the LPS group, L. reuteri increased the proportion of Proteobacteria and reduced the proportion of Firmicutes, changing the overall structure of the gut microbiota. It also influenced the fecal metabolites and changed the metabolite pathways, such as tyrosine metabolism, pentose and glucuronate interconversions, galactose metabolism, purine metabolism, and insulin resistance. These results showed thatL. reuteri is a potential therapy for AKI as it helps in sustaining the gut barrier integrity and modulating gut microbiota and related metabolites.

Rapid biotransformation of STW 5 constituents by human gut microbiome from IBS- and non-IBS donors.

STW 5 is an herbal medicinal product with proven clinical efficacy in the treatment of functional gastrointestinal disorders, like functional dyspepsia and irritable bowel syndrome (IBS). The effects of STW 5 on fecal microbial communities and metabolite production effects have been studied in an experimental model with fecal samples from individuals with and without IBS. While only minor taxonomic disparities were noted between IBS- and non-IBS samples and upon treatment with STW 5, rapid metabolic turnover of STW 5 components into specific degradation products with reported anti-inflammatory, cytoprotective, or spasmolytic activities was observed, which may be relevant for the pharmacological activity of STW 5.

Baoyuan decoction inhibits atherosclerosis progression through suppression peroxidized fatty acid and Src/MKK4/JNK pathway-mediated CD 36 expression

Background: Baoyuan decoction (BYD) has been widely utilized as a traditional prescription for the treatment of various conditions such as coronary heart disease, aplastic anemia, and chronic renal failure. However, its potential efficacy in improving atherosclerosis has not yet been investigated.Purpose: Our research aimed to assess the potential of BYD as an inhibitor of atherosclerosis and uncover the underlying mechanism by which it acts on foam cell formation.Study Design and Methods: High-fat diet-induced ApoE-/- mice were employed to explore the effect of BYD on atherosclerosis. The differential metabolites in feces were identified and analyzed by LC-Qtrap-MS. In addition, we utilized pharmacological inhibition of BYD on foam cell formation induced by oxLDL in THP-1 cells to elucidate the underlying mechanisms specifically in macrophages.Results: The atherosclerotic plaque burden in the aortic sinus of ApoE-/- mice was notably reduced with BYD treatment, despite no significant alterations in plasma lipids. Metabolomic analysis revealed that BYD suppressed the increased levels of peroxidized fatty acids, specifically 9/13-hydroxyoctadecadienoic acid (9/13-HODE), in the feces of mice. As a prominent peroxidized fatty acid found in oxLDL, we confirmed that 9/13-HODE induced the overexpression of CD36 in THP-1 macrophages by upregulating PPARγ. In subsequent experiments, the decreased levels of CD36 triggered by oxLDL were observed after BYD treatment. This decrease occurred through the regulation of the Src/MMK4/JNK pathway, resulting in the suppression of lipid deposition in THP-1 macrophages.Conclusions: These results illustrate that BYD exhibits potential anti-atherosclerotic effects by inhibiting CD36 expression to prevent foam cell formation.

Intestinal metabolite xylulose inhibits colorectal cancer by inducing apoptosis through the MAPK signalling pathway

BackgroundThe intestinal metabolites are involved in the initiation, progression and metastasis of colorectal cancer (CRC). They are a potential source of agents for cancer therapy. Our previous study identified altered faecal metabolites between CRC patients and healthy volunteers. However, no specific metabolite was clearly illustrated for CRC therapy. ResultsWe found that the level of xylulose was lower in the stools of CRC patients than in those of healthy volunteers. Xylulose inhibited cell growth without affecting the cell cycle by inducing apoptosis in CRC cells, which was evidenced by increased expression of the proapoptotic proteins C-PARP and C-Caspase3 and decreased expression of the antiapoptotic protein BCL-2 in CRC cells. Mechanistically, xylulose reduced the activity of the MAPK signalling pathway, represented by reduced phosphorylation of JNK, ERK, and P38. Furthermore, an ALI model was used to show the tumour killing ability of xylulose on human CRC spheres, as well as human colorectal adenoma (AD) spheres. ConclusionXylulose inhibits CRC growth by inducing apoptosis through attenuation of the MAPK signalling pathway. These results suggest that xylulose may serve as an effective agent for CRC therapy.

Associations of Plasma and Fecal Metabolites with Body Mass Index and Body Fat Distribution in Children.

Childhood obesity continues to be a critical public health concern with far-reaching implications for the well-being. This study aimed to investigate the association between metabolites in plasma and feces and indicators including body mass index (BMI), BMI for age Z score (BMIZ), and body fat distribution among children aged 6-9 years in China. This cross-sectional study enrolled 424 healthy children, including 186 girls and 238 boys. Dual-energy X-ray absorptiometry (DXA) was used to determine the body fat content and regional fat distribution. Plasma and fecal metabolites were analyzed using targeted metabolomic technologies. A total of 200 plasma metabolites and 212 fecal metabolites were accurately quantified via ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). By using Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) and random forest model, we discovered that 9 plasma metabolites and 11 fecal metabolites were associated with different weight statuses. After adjusting for potential covariates and false discovery rate (FDR) correction, multiple linear regression analyses revealed that plasma metabolites (fumaric acid, glycine, l-glutamine, methylmalonic acid, and succinic acid) and fecal metabolites (protocatechuic acid) were negatively associated (β: -1.373--0.016, pFDR: <0.001-0.031; β: -1.008--0.071, pFDR: 0.005-0.033), while plasma metabolites (isovaleric acid, isovalerylcarnitine, l-glutamic acid, and pyroglutamic acid) and fecal metabolites (3-aminoisobutanoic acid, butyric acid, N-acetylneuraminic acid, octanoylcarnitine, oleoylcarnitine, palmitoylcarnitine, stearoylcarnitine, taurochenodesoxycholic acid, and taurodeoxycholic acid) exhibited positive associations with BMI, BMIZ, and body fat distribution (β: 0.023-2.396, pFDR: <0.001; β: 0.014-1.736, pFDR: <0.001-0.049). Plasma and fecal metabolites such as glutamine may serve as a potential therapeutic target for the development of obesity.

Diet-omics in the Study of Urban and Rural Crohn disease Evolution (SOURCE) cohort

Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions.

Metabolomic and transcriptomic correlative analyses in germ free mice link probiotic-associated metabolites to host intestinal fatty acid metabolism and b-oxidation

While a transcriptomics-led examination of the effects of probiotics offers valuable insights into their influence on host gene regulation, the dynamic interactions between host metabolism and probiotics require an integrated analysis and multiomics approach to provide deeper insight into the underlying molecular mechanisms governing these associations. Here, we developed a high throughput bioinformatic tool ‘metabolome-transcriptome correlation analysis’ (METRCA, in press) that can determine whether a certain gene-metabolite association is up or downregulated and predict whether a metabolite’s or gene’s tissue location impacts its interaction with one another. To test this, we analyzed by LCMS and bulk-RNA sequencing then assessed linkages between serum as well as fecal metabolites and disease- or metabolism-associated genes in the ileum of gnotobiotic mice fed either a tryptophan (trp)-deficient or -suffcient diet then mono-associated with Lactobacillus rhamnosus GG (LGG) or administered PBS (control). We discovered significant associations, mainly in LGG mice fed trp, between metabolites and ileal genes involved in fatty acid metabolism (FAM) and oxidation (FAO). This association was specific and not observed in GF mice gavaged with PBS, monocolonized with R. gnavus, or fed trp- diets, and in SPF mice. Many fecal trp metabolites like indole-3-acetamide and serum trp metabolites like indole acetonitrile were significantly, positively correlated with important intestinal FAM genes Dgat1 and Mgat2. Likewise, numerous fecal metabolites like 5-hydroytrp and several serum trp metabolites like serotonin emerged as positively correlated metabolites with the rate-limiting FAO genes Acaa2 and Cpt2. Serum indoles were more strongly associated with both FAM and FAO genes than fecal indoles. Few fecal and serum metabolites were found negatively correlated with FAM and FAO genes. Since most are positive correlators, these findings suggest a testable hypothesis that LGG- and trp-dependent metabolites increase the intestinal metabolism of dietary lipids, providing a mechanism to previous findings that LGG supplementation in mice protected against diet-induced obesity and fatty liver disease. Analytical approaches like METRCA can thus be used to extract valuable information from metabolite and RNA-Seq datasets, generating novel hypotheses that may discover new interactions between microbe- or nutrient-associated metabolites and host metabolic or disease-related pathways. NIHR01-AT010243 (NG,RF), R01DK119198 (NG), NSF 1754783 (RF)). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The dissection of a despotic society: exploration, dominance and hormonal traits.

Naked mole-rats (Heterocephalus glaber) live in large colonies with one breeding female (queen), one to three breeding males (BMs) and the remainder are non-reproductive subordinates. The animals have a linear dominance rank with the breeders at the top of the hierarchy. We investigated how dominance rank in naked mole-rats differs with exploration (the propensity to explore a novel environment) and related endocrine markers. Exploration behaviour, faecal progestagen metabolite (fPM), faecal glucocorticoid metabolite (fGCM), faecal androgen metabolite (fAM) and plasma prolactin concentrations were quantified in breeding, high-, middle- and low-ranked females and males from five naked mole-rat colonies. There were no significant differences between the dominance rank and exploration behaviour. Interestingly, the queens and high-ranking females had higher fGCM and fAM concentrations compared with middle- and low-ranked females. The queens had significantly higher fPM concentrations than all other ranked females, since they are responsible for procreation. In the males, the BMs had higher fGCM concentrations compared with high- and low-ranked males. In addition, BMs and middle-ranking males had overall higher prolactin levels than all other ranked males, which could be linked to cooperative care. Overall, the results suggest that physiological reproductive suppression is linked to high dominance rank.

Unveiling the roles of dietary Tryptophan and Arginine metabolism in Lactobacillus rhamnosus GG-mediated barrier protection

Inflammatory bowel disease (IBD) is often characterized by increased intestinal paracellular permeability and abnormalities in tight junctions (TJ). IBD patients commonly exhibit reduced serum tryptophan (TRP) levels. Furthermore, animal models on low-TRP diets are more susceptible to chemically induced intestinal inflammation, while those on high-TRP diets show reduced inflammation. The interaction between TRP and gut microbiota in reinforcing the intestinal barrier warrants further investigation. To address this, we introduced Lactobacillus rhamnosus GG (LGG), known for enhancing the gut barrier, and PBS as a control into germ-free mice fed TRP-suffcient or -deficient diets. Our analysis of the mouse ileal transcriptome revealed dramatic upregulation of key genes in arginine metabolism only in LGG-TRP mice, particularly of argininosuccinate lyase ( Asl) that catabolizes argininosuccinate (ASA). Interestingly, our in-silico analysis of human IBD data GEO 179285 transcriptome showed marked dysregulation of similar genes, including inappropriate increases in ASA synthetase ( Ass1). Moreover, this unique expression pattern in the mouse ileum was TRP-dependent and specific to LGG, and not observed in mice monocolonized with pathobiont Ruminococcus gnavus or specific pathogen-free mice. LC-MS analysis of fecal and serum metabolites in LGG-TRP mice revealed elevated levels of fecal arginine, glutamine, and aspartate, suggesting their involvement in host arginine biosynthesis, along with significant reductions in serum ASA levels. ASA was highly negatively correlated with numerous TJ genes, suggesting its potential to compromise barrier function. Indeed, treating mouse enteroids with ASA enhanced dextran permeability, exacerbated LPS disruption of the gut barrier, and decreased expression of TJ genes Ocln and Tjp1. Furthermore, elevated serum ASA and decreased colonic ASL levels were observed in colitis-afflicted mice, perturbing gut homeostasis, as indicated by increased fecal lipocalin-2 and delayed colitis recovery after intraperitoneal ASA administration. We propose that LGG-TRP stimulates gut-mediated ASA turnover as evidenced by substantial increases in Asl levels. Interestingly, LGG alone reduced ASA concentration in the culture medium under anaerobic and aerobic conditions. Collectively, our study identifies ASA as a potential biomarker of gut inflammation and enhanced permeability. Moreover, we highlight the potential of LGG-TRP therapy for IBD-associated leaky gut conditions, offering novel insights for gut health interventions. NIHR01-AT010243 (NG,RF), R01DK119198 (NG), NSF 1754783 (RF). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lingguizhugan Decoction Improved Obesity by Modulating the Gut Microbiota and its Metabolites in Mice.

The global obese population is rapidly increasing, urgently requiring the development of effective and safe weight-loss medications. The classic Chinese medicine formulation Lingguizhugan De-coction has exerted a significant anti-obesity effect. However, the underlying mechanism is still unclear. This study aimed to explore the mechanism of LGZGD in the treatment of obesity based on the gut microbiota and its metabolites. Three different dosages of LGZGD were gavaged to ob/ob mice for 8 weeks. Body mass and visceral fat mass were evaluated. Additionally, the changes in gut microbiota, fecal and plasma metabolites in mice after LGZGD treatment were analyzed by metagenomics and non-targeted metabolomics. The results demonstrated a significant anti-obesity effect of LGZGD treatment in ob/ob mice. Fur-thermore, the metagenomic analysis revealed that LGZGD reduced the ratio of Firmicutes / Bacteroidetes (F to B) in the gut, restored gut microbiota diversity, and identified 3 enriched KEGG pathways, including energy metabolism, lipid metabolism, and energy production and conversion pathways. Based on non-targeted metab-olomics analysis, 20 key metabolites in the feces and 30 key metabolites in the plasma responding to LGZGD treatment were identified, and the levels of Eicosapentaenoic acid (EPA) and Myristoleic acid (MA) might be the metabolites related to gut microbiota after LGZGD treatment. Their biological functions were mainly re-lated to the metabolism pathway. These findings suggested that LGZGD had therapeutic potential for obesity. The mechanism of LGZGD alleviating obesity was associated with improving dysbiosis of the gut microbiota. LDZGD affected gut microbiota-derived metabolites of EPA and MA and may act on energy metabolism pathways.

A Comparison of LED with Fluorescent Lighting on the Stress, Behavior, and Reproductive Success of Laboratory Zebra Finches (Taeniopygia guttata).

There are limited evidence-based husbandry recommendations for laboratory zebra finches (Taeniopygia guttata), including appropriate light sources. Light-emitting diode (LED) technology has been shown to improve circadian regulation and reduce stress in some laboratory animal species, such as mice and rats, when compared with cool-white fluorescent (CWF) lighting, but the effects of LED lighting on zebra finches have not been published. We compared the effects of broad-spectrum, blue-enriched (6,500 Kelvin) CWF and flicker-free LED lighting on the behavior, stress, and reproductive outcomes of indoor-housed zebra finches. Using breeding pairs housed in cubicles illuminated with either CWF or LED lighting, we compared the reproductive output as determined by clutch size, hatching rate, and hatchling survival rate. We also compared the behavior of group-housed adult males, first housed under CWF followed by LED lighting, using video recordings and an ethogram. Fecal samples were collected from these males at the end of each recording period, and basal fecal corticosterone metabolite (FCM) levels were compared. A FCM assay for adult male zebra finches was validated for efficacy and accuracy using a capture-restraint acute stress response and parallelism analysis, respectively. The breeding pairs had no significant difference in the clutch size or percent hatching rate, but percent hatchling survival improved under LED with an increased proportion achieving 100% survival. There was no significant difference in FCM between the lighting treatments. However, the activity budgets of the birds were altered, with a reduction in flighted movement and an increase in enrichment manipulation under LED. Overall, these results support the use of blue-enriched, broad-spectrum flicker-free LED as a safe alternative to CWF lighting for breeding and nonbreeding indoor-housed zebra finches.

Feasibility of a Sprague???Dawley Rat Model for Investigating the Effects of Seated Whole-body Vibration.

Vehicular whole-body vibration (WBV) can have long-term adverse effects on human quality of life. Animal models can be used to study pathophysiologic effects of vibration. The goal of this study was to assess animal cooperation and well-being to determine the feasibility of a novel seated rat model for investigating the effects of WBV on biologic systems. Twenty-four male Sprague???Dawley rats were used. The experiment consisted of an acclimation phase, 2 training phases (TrP1 and TrP2), and a testing phase (TeP), including weekly radiographic imaging. During acclimation, rats were housed in pairs in standard cages without vibration. First, experimental (EG; n = 18) and control group 1 (C1; n = 3) rats were placed in a vibration apparatus without vibration, with increasing duration over 5 d during TrP1. EG rats were exposed to vertical random WBV that was increased in magnitude over 5 d during TrP2 until reaching the vibration signal used during TeP (15min, 0.7m??s-2 root mean square, unweighted). C1 rats were placed in the vibration apparatus but received no vibration during any phase. Control group 2 (C2; n = 3) rats remained in the home cages. Cooperation was evaluated with regard to rat-apparatus interactions and position compliance. Behavior, weight, and fecal glucocorticoid metabolite concentrations (fGCM) were used to evaluate animal well-being. We observed good cooperation and no behavioral patterns or weight loss between phases, indicating little or no animal stress. The differences in fGCM concentration between groups indicated that the EG rats had lower stress levels than the control rats in all phases except TrP1. Thus, this model elicited little or no stress in the conscious, unrestrained, seated rats.

Gut-muscle axis: establishing the connection between microbial signaling and skeletal muscle function in a mouse model (mdx) of Duchenne muscular dystrophy

The metabolic and endocrine nature of skeletal muscle allows for systemic signaling and influence over the enteric environment influencing gut microbial populations. Concomitantly, commensal microbial signaling can alter the composition and development of skeletal muscle forming a bidirectional gut-muscle axis. Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease characterised by skeletal muscle atrophy, fibrosis, and ultimately cardiorespiratory failure. Previous studies have shown that gut microbial signaling can alter the pathways involved in muscle atrophy, enhancing atrophy when dysbiotic, or blunting the atrophic effect by restoring gut microbial populations to a healthy status; thus, we sought to characterize the metabolic signaling between the gut and the diaphragm in a mouse model of DMD ( mdx) to identify potential therapeutic targets. The study was divided into two arms and conducted following institutional ethical approval. The first arm investigated metabolomic signalling. 6-month-old male BL10 wildtype (WT; n = 12) and mdx (n = 12) mice were anaesthetized (induction by 5% isoflurane) and decapitated. Following collection of trunk blood, the diaphragm was excised, and colonic/cecal contents were collected. The samples were then processed by mass-spectrometry to isolate the metabolomic profiles of semi-polar, secondary bile acid, and short chain fatty acid (SCFA) targets in the gut, plasma and diaphragm of WT and mdx mice. The second arm of the study explored the gut microbial profile and diaphragm gene expression, structure and function. 6-month-old male WT (n = 15) and mdx (n = 15) were anesthetized (induction by 5% isoflurane) followed by cervical dislocation. The diaphragm was excised, and longitudinal strips were isolated for structural analysis (i.e., histological staining and immunohistochemistry for fibre type and size), PCR gene expression, and isometric force assessment ex vivo. Additionally, faecal pellets were collected and analysed via shotgun metagenomic sequencing to assess microbial populations. Diaphragm twitch and tetanic force in mdx were profoundly decreased compared to WT. Metabolic analysis of faecal metabolites indicated impairment in the three main tryptophan metabolic pathways in mdx mice: kynurenine, indole and serotonin. Metagenomic analysis indicated a profound genotype effect between WT and mdx gut microbial populations. Two main producers of the short chain fatty acid acetate (Lactobacillus and Bifidobacterium) were significantly decreased within the mdx group. Acetate serves as a substate in the TCA cycle contributing to ATP production and positively affects skeletal muscle via numerous pathways including the down regulation of key atrogenes associated with atrophy. Pathway enrichment analysis showed a global disruption to both purine and pyrimidine metabolism in all three tissue types. Purine/pyrimidine metabolism have been tightly linked with microbial metabolism and affect skeletal muscle health and function. Further understanding of the gut-muscle axis in dystrophic models may pave the way for novel microbiota-directed therapeutic strategies to ameliorate muscle dysfunction in DMD. Funded by Science Foundation Ireland SFI/19/6628 INSPIRE DMD. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lactiplantibacillus plantarum JS19-assisted fermented goat milk alleviates d-galactose-induced aging by modulating oxidative stress and intestinal microbiota in mice

Oxidative stress is a crucial factor in the age-related decline in physiological, genomic, metabolic, and immunological functions. We screened Lactiplantibacillus plantarum JS19 (L. plantarum JS19), which has been shown to possess therapeutic properties in mice with ulcerative colitis. In this study, L. plantarum JS19-adjunctly fermented goat milk (LAF) was employed to alleviate D-galactose-induced aging and regulate intestinal flora in an aging mouse model. The oral administration of LAF effectively improved the health of spleen and kidney in mice, while mitigating the hepatocyte and oxidative damage induced by D-galactose. Additionally, LAF alleviated D-galactose-induced dysbiosis of the intestinal flora by reducing the abundance of harmful bacteria Desulfovibrio and Helicobacter, while greatly promoting the growth of beneficial Rikenellaceae_RC9_gut_group and Eubacterium. Biomarker 5-hydroxyindole-3-acetic acid was found to be positively linked with those harmful bacteria, while bio-active metabolites were strongly correlated with the beneficial genus. These observations suggest that LAF possesses the capability to mitigate the effects of D-galactose-induced aging in a mouse model through the regulation of oxidative stress, the gut microbiota composition, and levels of fecal metabolites. Consequently, these findings shed light on the potential of LAF as a functional food with anti-aging properties.

The Effects of Fermented Rice Drink With Lactiplantibacillus plantarum JSA22 in Overweight Irritable Bowel Syndrome Patients: A Randomized, Double-blind, Placebo-controlled Study.

This study aims to investigate the effect of a fermented rice drink with Lactiplantibacillus plantarum JSA22 on symptoms, blood tests, microbiomes, and fecal metabolites in patients with irritable bowel syndrome (IBS) who were overweight. Sixty overweight (body mass index ≥ 23 kg/m2) patients aged between 20 and 65 with IBS were enrolled. Patients were divided into 2 groups and administered either a fermented rice drink or an nonfermented rice drink for a month. The symptom questionnaire, blood samples, and stool samples for microbiome and metabolite were collected before and after the month of rice drink administration. The primary efficacy variable was the subject's global assessment of IBS symptoms. In both groups, global IBS symptoms, including abdominal pain, bowel habit, urgency, and abdominal distension, improved significantly (P < 0.01). The abdominal bloating was more significantly improved in the fermented rice drink group than in the nonfermented rice drink group (P < 0.05). Significant changes were not observed in metabolic syndrome-related blood tests or fecal metabolites in either group. However, microbiome analysis showed significant differences in genus levels before and after consuming fermented rice drink, such as in Blautia in stool (P = 0.020) and Prevotella (P = 0.017) and Oribacterium (P = 0.018) in saliva. The fermented rice drink with L. plantarum JSA22 showed a beneficial effect in reducing abdominal distension in IBS patients. Bacteria that reduce visceral fat accumulation increased in the stool and saliva of patients who consumed fermented rice drinks.

A multi-omics approach to investigate characteristics of gut microbiota and metabolites in hypertension and diabetic nephropathy SPF rat models.

Imbalance in intestinal microbiota caused by microbial species and proportions or metabolites derived from microbes are associated with hypertension, as well as diabetic nephropathy. However, the involvement of the intestinal microbiota and metabolites in hypertension and diabetic nephropathy comorbidities (HDN) remains to be elucidated. We investigated the effects of intestinal microbiota on HDN in a rat model and determined the abundance of the intestinal microbiota using 16S rRNA sequencing. Changes in fecal and serum metabolites were analyzed using ultra-high-performance liquid chromatography-mass spectrometry. The results showed abundance of Proteobacteria and Verrucomicrobia was substantially higher, whereas that of Bacteroidetes was significant lower in the HDN group than in the sham group. Akkermansia, Bacteroides, Blautia, Turicibacter, Lactobacillus, Romboutsia, and Fusicatenibacter were the most abundant, and Prevotella, Lachnospiraceae_NK4A136_group, and Prevotella_9 were the least abundant in the HDN group. Further analysis with bile acid metabolites in serum showed that Blautia was negatively correlated with taurochenodeoxycholic acid, taurocholic acid, positively correlated with cholic acid and glycocholic acid in serum. These findings suggest that the gut microbiota and metabolites in feces and serum substantially differed between the HDN and sham groups. The F/B ratio was higher in the HDN group than in the sham group. Blautia is potentially associated with HDN that correlated with differentially expressed bile acid metabolites, which might regulate the pathogenesis of HDN via the microorganism-gut-metabolite axis.

Connection of pre-competition anxiety with gut microbiota and metabolites in wrestlers with varying sports performances based on brain-gut axis theory

ObjectiveThe purpose of this study is to investigate the connection of pre-competition anxiety with gut microbiota and metabolites in wrestlers with different sports performances.MethodsOne week prior to a national competition, 12 wrestlers completed anxiety questionnaires. Faecal and urine samples were collected for the analysis of gut microbiota and metabolites through the high-throughput sequencing of the 16 S rRNA gene in conjunction with untargeted metabolomics technology. The subjects were divided into two groups, namely, achievement (CP) and no-achievement (CnP) wrestlers, on the basis of whether or not their performances placed them in the top 16 at the competition. The relationship amongst the variations in gut microbiota, metabolites, and anxiety indicators was analyzed.Results(1) The CP group exhibited significantly higher levels of “state self-confidence,” “self-confidence,” and “somatic state anxiety” than the CnP group. Conversely, the CP group displayed lower levels of “individual failure anxiety” and “sports competition anxiety” than the CnP group. (2) The gut microbiota in the CP group was more diverse and abundant than that in the CnP group. Pre-competition anxiety was linked to Oscillospiraceae UCG_005, Paraprevotella, Ruminococcaceae and TM7x. (3) The functions of differential metabolites in faeces and urine of the CP/CnP group were mainly enriched in caffeine metabolism, lipopolysaccharide biosynthesis and VEGF and mTOR signaling pathways. Common differential metabolites in feces and urine were significantly associated with multiple anxiety indicators.ConclusionsWrestlers with different sports performance have different pre-competition anxiety states, gut microbiota distribution and abundance and differential metabolites in faeces and urine. A certain correlation exists between these psychological and physiological indicators.

Illumina Sequencing and Metabolomic Analysis Explored the Effects of the Mixed Silage of Rice Straw and Chinese Cabbage Waste on Fecal Microorganisms and Metabolites in Hu Sheep

Silage is the most important component of a ruminant diet and has important production and health significance in ruminant production. The aim of the research was to investigate how the mixed silage of Chinese cabbage waste and rice straw (mixed silage) impacts the fecal microorganisms and metabolites in Hu sheep using Illumina sequencing and metabolomic analysis. A total of 16 Hu sheep (8 rams and 8 ewes) weighing about 39 kg and 5.5 months old were used as experimental sheep and divided into two groups (4 rams and 4 ewes, n = 8) using the principle of randomized trials: the control group with peanut sprouts, corn husks, and sorghum husks as roughage and the silage group with the mixed silage as roughage. There were no significant differences in the average daily gain (ADG), dry matter intake (DMI), or feed conversion rate (FCR) between the control group and the mixed silage groups (p &gt; 0.05). Microbiome results showed that 15 microorganisms such as Ruminococcaceae UCG 010, Breznakia, Erysipelothrix, Desulfovibrio, Succiniclasticum, and Shuttleworthia were significantly different between the two groups. In addition, metabolomics showed that the mixed silage modulated the concentrations and metabolic pathways of metabolites in the manure. Significantly different metabolites were mainly enriched in amino acid anabolism (“glycine, serine, and threonine metabolism”, “valine, leucine, and isoleucine biosynthesis”, “arginine biosynthesis”, etc.), nucleic acid metabolism (pyrimidine metabolism). In conclusion, the addition of mixed silage to the diet of Hu sheep can alter the structure of the hindgut microflora and regulate the metabolism of amino acids and nucleotides, which affects health performance.

The Potential Mechanism of the Anti-Liver Fibrotic Effect of Curcumin in the Gut-Liver Axis.

This study aimed to explore the curative effect of curcumin on liver fibrosis and its correlation with the gut-liver axis in animal models. Histological staining was utilized to conduct histological analysis of the liver and intestine. An automatic biochemical analyzer or enzyme-linked immunosorbent assay system was utilized for analyzing the biochemical indexes in mice. Western blotting was employed to examine the level of relevant proteins. Furthermore, 16S rRNA high-throughput sequencing was performed to explore the impact of curcumin on intestinal microorganisms in rats with liver fibrosis. Ultrahigh-performance liquid chromatography with quadrupole-orbitrap mass spectrometry was utilized to analyze the effect of curcumin on rat feces metabolites. Our results showed that curcumin reduced the formation of collagen fibers caused by carbon tetrachloride in a dose-dependent manner. In addition, curcumin was able to restore intestinal permeability in rats with liver fibrosis. By adopting α diversity analysis (Chao 1 index, Shannon index, and Simpson index), we observed that both the diversity and the abundance of intestinal flora in rats with liver fibrosis were increased. The principal component analysis diagram demonstrated that curcumin could enhance the abundance and diversity of intestinal flora, and also restore the composition of model rat flora, which was similar to that in normal rats, thereby correcting the imbalance of flora in rats with liver fibrosis. In addition, curcumin regulated feces metabolites and their signaling pathways, including glycerophospholipid metabolism, pantothenate and CoA biosynthesis. Our findings suggest that curcumin exhibits antiliver fibrosis effects, and its antiliver fibrosis effects might correlate with gut-liver axis.