Search

Background: The human gut environment undergoes substantial changes as a host ages. This investigation centered on the gut microbiome diversity among patients with severe motor and intellectual disabilities (SMID), examining the association between the gut microbiome composition and physical characteristics with varying levels of diversity. Methods: Fourteen subjects were investigated, with physical and defecation status, blood biochemical test, gut microbiome profiling, and fecal metabolites used to divide the patients into a high-diversity group (HD, eight patients) and a low-diversity group (LD, six patients). Results: Findings indicated that the microbiome of the LD group showed delayed maturation reminiscent of neonates and lactating infants. Analysis of the fecal bile acids (BAs) revealed a markedly diminished proportion of deoxycholic acid in the secondary BAs in the LD group, suggestive of inadequate conversion from primary to secondary BAs. Furthermore, the LD group presented with loose stools. The LD group exhibited a higher degree of physical severity, with all patients bedridden and fed via gastrostomy with only enteral formula received. Conclusions: The composition of the gut microbiome and BAs in the LD group was found to differ from those of healthy individuals and the HD group, indicating a potentially immature gut environment for these individuals. [ABSTRACT FROM AUTHOR]

Background: Gut microbial composition and its metabolites are crucial for livestock production performance. Metabolite profiles from autopsied biospecimens provide vital information on the basic mechanisms that affect the overall health and production traits in livestock animals. However, the role of the host breed in the gut microbiome and fecal metabolome of commercial pigs remains unclear. In this work, differences in microbiota composition among three commercial pig breeds Duroc, Yorkshire, and Landrace were measured by 16S rRNA gene sequencing. Fecal metabolite compositions of the three pig breeds were detected using untargeted metabolomics. Results: There were significant differences in the gut microbiomes of the three species, indicating that host breed affects the diversity and structure of gut microbiota. Several breed-associated microorganisms were identified at different taxonomic levels. Notely, most microbial taxa were annotated as Lactobacillacea, Muribaculaceae, and Oscillospiraceae. Several bacteria, including Lactobacillus, Subdoligranulum, Faecalibacterium, Oscillospira, Oscillospiraceae_UCG-002, and Christensenellaceae_R-7_group, could be considered as biomarkers for improving the backfat thickness (BF) for commercial pigs. Additionally, KEGG analysis of gut microbiota further revealed that arginine biosynthesis, pyruvate metabolism, and fatty acid biosynthesis varied greatly among pig breeds. Multiple gut bacterial metabolites (e.g., spermidine, estradiol, and palmitic acid) were identified as breed-associated. Mediation analysis ultimately revealed the cross-talk among gut microbiota, metabolites, and BF thickness, proclaiming that the microbial and metabolic biomarkers identified in this study could be used as biomarkers for improving BF phenotype. Conclusions: This work provides vital insights into breed effects on gut microbiota and metabolite compositions of commercial pigs and uncovers potential biomarkers that are significant for pig breed improvement. [ABSTRACT FROM AUTHOR]

Wild rice (WLD) attenuated hyperglycemia, hyperlipidemia and chronic inflammation in mice receiving a high-fat diet (HFD) versus white rice (WHR), but the underlying mechanism is not well understood. We examined the influence of HFD + WLD on gut microbiota, short chain fatty acids (SCFAs) and the correlation with metabolic or inflammatory markers in mice versus HFD + WHR. C57BL/6J mice received HFD + 26 g weight (wt) % WHR or WLD or 13 g wt% WHR + 13 g wt% WLD (WTWD) for 12 weeks. Plasma levels of glucose, cholesterol and triglycerides, insulin resistance and inflammatory markers after overnight fasting were lower, and the abundances of fecal Lactobacillus gasseri and propionic acid were higher in HFD + WLD-fed mice than in HFD + WHR-fed mice. The anti-inflammatory effects of HFD + WTWD were weaker than HFD + WLD but were greater than those in HFD + WHR-fed mice. Abundances of fecal Lactobacillus gasseri and propionic acid in mice receiving HFD + WLD were higher than those in mice fed with HFD + WHR. The abundances of fecal L. gasseri and propionic acid negatively correlated with metabolic and inflammatory markers. The findings of the present study suggest that WLD attenuated metabolic and inflammatory disorders in mice on HFD. Interactions between WLD components and gut microbiota may upregulate fecal SCFAs, and the latter may be attributed to the benefits of WLD on metabolism and inflammation in mice on HFD. [ABSTRACT FROM AUTHOR]

Abstract Background Gut microbial composition and its metabolites are crucial for livestock production performance. Metabolite profiles from autopsied biospecimens provide vital information on the basic mechanisms that affect the overall health and production traits in livestock animals. However, the role of the host breed in the gut microbiome and fecal metabolome of commercial pigs remains unclear. In this work, differences in microbiota composition among three commercial pig breeds Duroc, Yorkshire, and Landrace were measured by 16S rRNA gene sequencing. Fecal metabolite compositions of the three pig breeds were detected using untargeted metabolomics. Results There were significant differences in the gut microbiomes of the three species, indicating that host breed affects the diversity and structure of gut microbiota. Several breed-associated microorganisms were identified at different taxonomic levels. Notely, most microbial taxa were annotated as Lactobacillacea , Muribaculaceae, and Oscillospiraceae. Several bacteria, including Lactobacillus, Subdoligranulum, Faecalibacterium, Oscillospira, Oscillospiraceae_UCG-002, and Christensenellaceae_R-7_group, could be considered as biomarkers for improving the backfat thickness (BF) for commercial pigs. Additionally, KEGG analysis of gut microbiota further revealed that arginine biosynthesis, pyruvate metabolism, and fatty acid biosynthesis varied greatly among pig breeds. Multiple gut bacterial metabolites (e.g., spermidine, estradiol, and palmitic acid) were identified as breed-associated. Mediation analysis ultimately revealed the cross-talk among gut microbiota, metabolites, and BF thickness, proclaiming that the microbial and metabolic biomarkers identified in this study could be used as biomarkers for improving BF phenotype. Conclusions This work provides vital insights into breed effects on gut microbiota and metabolite compositions of commercial pigs and uncovers potential biomarkers that are significant for pig breed improvement.

Abstract Background Multiple 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. Methods A 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. Results A 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. Conclusions Different stages of 131I therapy exert various effects on gut microecology, which play an essential role in regulating radiotoxicity and predicting the therapeutic response.

Background: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. Methods: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. Results: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. Conclusion: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects. [ABSTRACT FROM AUTHOR]

In this study, we investigated the correlation between the composition and function of the gut microbiota and the semen quality of Rongchang boars. Significant differences in gut microbial composition between boars with high (group H) and low (group L) semen utilization rates were identified through 16S rRNA gene sequencing, with 18 differential microbes observed at the genus level. Boars with lower semen utilization rates exhibited a higher relative abundance of Treponema, suggesting its potential role in reducing semen quality. Conversely, boars with higher semen utilization rates showed increased relative abundances of Terrisporobacter, Turicibacter, Stenotrophomonas, Clostridium sensu stricto 3, and Bifidobacterium, with Stenotrophomonas and Clostridium sensu stricto 3 showing a significant positive correlation with semen utilization rates. The metabolomic analyses revealed higher levels of gluconolactone, D-ribose, and 4-pyridoxic acid in the H group, with 4 pyridoxic acid and D-ribose showing a significant positive correlation with Terrisporobacter and Clostridium sensu stricto 3, respectively. In contrast, the L group showed elevated levels of D-erythrose-4-phosphate, which correlated negatively with Bifidobacterium and Clostridium sensu stricto 3. These differential metabolites were enriched in the pentose phosphate pathway, vitamin B6 metabolism, and antifolate resistance, potentially influencing semen quality. These findings provide new insights into the complex interplay between the gut microbiota and boar reproductive health and may offer important information for the discovery of disease biomarkers and reproductive health management. [ABSTRACT FROM AUTHOR]

Fermented foods have shown promise in preventing or treating ulcerative colitis (UC) via regulating intestinal flora and correcting metabolic disorders. However, the prevention effect of fermented Wallace melon juice (FMJ) on UC is unclear. In this study, the effects of FMJ on dextran sodium sulfate (DSS)‐induced UC were investigated via 16S rRNA sequencing and non‐targeted metabolomics. The results showed that FMJ was effective in alleviating the symptoms of UC, reducing histological damage and oxidative stress, decreasing the levels of pro‐inflammatory cytokines. After FMJ treatment, the level of propionic acid, butyric acid, and valeric acid increased by 14.1%, 44.4%, and 52.4% compared to DSS‐induced UC mice. Meanwhile, the levels of harmful bacteria such as Oscillospira, Bacteroidetes, and Erysipelotrichaceae and Clostridium decreased, while the levels of beneficial bacteria such as Akkermansia, Lactobacillus, and Bifidobacterium increased. Fecal metabolomics analysis identified 31 differential metabolites, which could regulate metabolic disorders in UC mice by controlling the primary bile acid biosynthesis, purine metabolism, and pantothenate and CoA biosynthesis pathway. Additionally, the abundances of butyric acid, bile acids, and pantothenic acid were positively correlated with Allobaculum, Bifidobacterium, and other beneficial bacteria (R2 > 0.80, p < 0.01). The results indicated that FMJ played a role in regulating the structure of intestinal flora, which in turn helped in repairing metabolic disorders and alleviated colitis inflammation. [ABSTRACT FROM AUTHOR]

Background: The potential of the fecal metabolome to serve as a biomarker for irritable bowel syndrome (IBS) depends on its stability over time. Therefore, this study aimed to determine the temporal dynamics of the fecal metabolome, and the potential relationship with stool consistency, in patients with IBS and healthy subjects. Methods: Fecal samples were collected in two cohorts comprising patients with IBS and healthy subjects. For Cohort A, fecal samples collected during 5 consecutive days were analyzed by gas chromatography‐tandem mass spectrometry (GC–MS/MS). For Cohort B, liquid chromatography‐MS (LC–MS) was used to analyze fecal samples collected at week 0 (healthy and IBS) and at week 4 (patients only). Stool consistency was determined by the Bristol Stool Form scale. Key Results: Fecal samples were collected from Cohort A (seven healthy subjects and eight IBS patients), and Cohort B (seven healthy subjects and 11 IBS patients). The fecal metabolome of IBS patients was stable short‐term (Cohort A, 5 days and within the same day) and long‐term (Cohort B, 4 weeks). A similar trend was observed over 5 days in the healthy subjects of Cohort A. The metabolome dissimilarity was larger between than within participants over time in both healthy subjects and IBS patients. Further analyses showed that patients had greater range of stool forms (types) than healthy subjects, with no apparent influence on metabolomic dynamics. Conclusion & Inferences: The fecal metabolome is stable over time within IBS patients as well as healthy subjects. This supports the concept of a stable fecal metabolome in IBS despite fluctuations in stool consistency, and the use of single timepoint sampling to further explore how the fecal metabolome is related to IBS pathogenesis. [ABSTRACT FROM AUTHOR]

ABSTRACT Gut bacteria belonging to the Clostridium family play a pivotal role in regulating host energy balance and metabolic homeostasis. As a commensal bacterium, Clostridium sporogenes has been implicated in modulating host energy homeostasis, albeit the underlying mechanism remains elusive. Therefore, this study aimed to investigate the impact of C. sporogenes supplementation on various physiological parameters, intestinal morphology, particularly adipose tissue accumulation, and glucolipid metabolism in mice. The findings reveal that mice supplemented with C. sporogenes for 6 weeks exhibited a notable increase in body weight, fat mass, adipocyte size, and serum triglyceride (TG) levels. Notably, the increased fat accumulation is observed despite consistent feed intake in treated mice. Mechanistically, C. sporogenes supplementation significantly improved the structure integrity of intestinal villi and enhanced energy absorption efficiency while reducing excretion of carbohydrates and fatty acids in feces. This was accompanied by upregulation of glucose and fatty acid transporter expression. Furthermore, supplementation with C. sporogenes promoted adipogenesis in both liver and adipose tissues, as evidenced by increased levels of hepatic pyruvate, acetyl-CoA, and TG, along with elevated expression levels of genes associated with lipid synthesis. Regarding the microbiological aspect, C. sporogenes supplementation correlated with an increased abundance of Clostridium genus bacteria and enhanced carbohydrate enzyme activity. In summary, C. sporogenes supplementation significantly promotes fat accumulation in mice by augmenting energy absorption and adipogenesis, possibly mediated by the expansion of Clostridium bacteria population with robust glycolipid metabolic ability.IMPORTANCEThe Clostridia clusters have been implicated in energy metabolism, the specific species and underlying mechanisms remain unclear. This present study is the first to report Clostridium sporogenes is able to affect fat accumulation and glycolipid metabolism. We indicated that gavage of C. sporogenes promoted the adipogenesis and fat accumulation in mice by not only increasing the abundance of Clostridium bacteria but by also enhancing the metabolic absorption of carbohydrates and fatty acids significantly. Obviously, changes of gut microbiota caused by the C. sporogenes, especially the significant increase of Clostridium bacteria, contributed to the fat accumulation of mice. In addition, the enhancement of Clostridium genus bacteria remarkably improved the synthesis of hepatic pyruvate, acetyl-CoA, and triglyceride levels, as well as reduced the excretion of fecal carbohydrates, short-chain fatty acids, and free fatty acids remarkably. These findings will help us to understand the relationship of specific bacteria and host energy homeostasis.

Background: Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA. Methods: We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules. Results: During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the Bifidobacterium-dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kUA/L increments, 0.67 and 0.66; 95%CI, 0.41–0.93 and 0.42–0.90; Bifidobacterium-dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10–2.03), and these associations were observed until the end of OIT. Conclusions: In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT.

Oral immunotherapy (OIT) can ameliorate cow's milk allergy (CMA); however, the achievement of sustained unresponsiveness (SU) is challenging. Regarding the pathogenesis of CMA, recent studies have shown the importance of gut microbiota (Mb) and fecal water-soluble metabolites (WSMs), which prompted us to determine the change in clinical and gut environmental factors important for acquiring SU after OIT for CMA. We conducted an ancillary cohort study of a multicenter randomized, parallel-group, delayed-start design study on 32 school-age children with IgE-mediated CMA who underwent OIT for 13 months. We defined SU as the ability to consume cow's milk exceeding the target dose in a double-blind placebo-controlled food challenge after OIT followed by a 2-week-avoidance. We longitudinally collected 175 fecal specimens and clustered the microbiome and metabolome data into 29 Mb- and 12 WSM-modules. During OIT, immunological factors improved in all participants. However, of the 32 participants, 4 withdrew because of adverse events, and only 7 were judged SU. Gut environmental factors shifted during OIT, but only in the beginning, and returned to the baseline at the end. Of these factors, milk- and casein-specific IgE and the Bifidobacterium -dominant module were associated with SU (milk- and casein-specific IgE; OR for 10 kU A /L increments, 0.67 and 0.66; 95%CI, 0.41–0.93 and 0.42–0.90; Bifidobacterium -dominant module; OR for 0.01 increments, 1.40; 95%CI, 1.10–2.03), and these associations were observed until the end of OIT. In this study, we identified the clinical and gut environmental factors associated with SU acquisition in CM-OIT. [ABSTRACT FROM AUTHOR]

Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn's disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGFβ superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and/or perpetuation of inflammation in CD. [ABSTRACT FROM AUTHOR]

Introduction: Gut microbiota and metabolites have been identified to contribute to the pathogenesis of functional constipation (FC); however, the underlying mechanism(s) have not been elucidated, and the relationship between the gut microbiota and metabolites in FC has received limited attention in the literature. Methods: 16S rDNA sequencing and non-targeted metabolomic detection based on liquid chromatography-mass spectrometry (LC-MS/MS) technologies were combined to analyze the altered gut microbiome and metabolic profile of fecal samples from FC patients and healthy individuals (healthy control; HC). Results: The richness and diversity of gut microbiota significantly (p < 0.01) increased in FC patients. Compared to the HC group, 18 genera, including Intestinibacter, Klebsiella, and Akkermansia, exhibited statistically significant changes (p < 0.05). Metabolic analysis showed that metabolic profiles were also markedly altered with 79 metabolites, such as (-)-caryophyllene oxide, chenodeoxycholic acid, and biliverdin, indicating significant inter-group differences (p < 0.05). Besides, the primary bile acid biosynthesis, as well as the metabolic profile of porphyrin and chlorophyll, were the most dominant enriched pathways (FDR < 0.01), in which chenodeoxycholic acid and biliverdin were significantly enriched, respectively. Correlation analysis demonstrated a strong relationship between 10 genera and 19 metabolites (r > 0.6, FDR < 0.05), and notably, Intestinibacter showed a negative correlation with biliverdin (FDR < 0.001), which highlighted the interplay of the gut microbiota and metabolites in the pathogenesis of FC. Conclusion: Our research describes the characteristics of the gut microbiota and metabolic profiles and the correlation between the gutmicrobiota andmetabolites in FC patients. This may contribute to the understanding of the underlying mechanisms involved in FC pathogenesis and may provide novel insights into therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Hepatic ischemia–reperfusion injury (HIRI) is a common complication of liver surgery, which can lead to extrahepatic metabolic disorders, such as cognitive impairment. Recent observations have emphasized the critical effects of gut microbial metabolites in regulating the development of liver injury. Herein, we investigated the potential contribution of gut microbiota to HIRI-related cognitive impairment. Methods: HIRI murine models were established by ischemia–reperfusion surgery in the morning (ZT0, 08:00) and evening (ZT12, 20:00), respectively. Antibiotic-induced pseudo-germ-free mice were gavaged with fecal bacteria of the HIRI models. Behavioral test was used to assess cognitive function. 16S rRNA gene sequencing and metabolomics were used for microbial and hippocampal analysis. Results: Our results established that cognitive impairment caused by HIRI underwent diurnal oscillations; HIRI mice performed poorly on the Y-maze test and the novel object preference test when surgery occurred in the evening compared with the morning. In addition, fecal microbiota transplantation (FMT) from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior. The specific composition and metabolites of gut microbiota were analyzed between the ZT0-HIRI and ZT12-HIRI, and bioinformatic analysis showed that the differential fecal metabolites were significantly enriched in lipid metabolism pathways. After FMT, the hippocampal lipid metabolome between the P-ZT0-HIRI and P-ZT12-HIRI groups was analyzed to reveal a series of lipid molecules with significant differences. Conclusions: Our findings indicate that gut microbiota are involved in circadian differences of HIRI-related cognitive impairment by affecting hippocampal lipid metabolism. [ABSTRACT FROM AUTHOR]

An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia. Bifidobacterium longum (B. longum) CCFM1077 has been shown to have lipid-lowering effects in animals. This study aimed to evaluate the potential of B. longum CCFM1077 in lowering the lipid levels in patients with hyperlipidemia and investigate the effect of this bacterium on serum lipid abnormalities, gut microbiota, and fecal metabolites in these patients. This study was a six-week, randomized, double-blind, and placebo-controlled pilot clinical trial. Subjects with hyperlipidemia (N = 62) were randomly assigned to receive placebo (N = 31) or B. longum CCFM1077 (1 × 1010 colony-forming units (CFUs) per day; N = 31). Serum lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), total triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were examined at the baseline and interventional endpoints. Changes in the gut microbiota composition and diversity were measured based on 16S ribosomal RNA (rRNA) sequencing of the V3–V4 region at the end of the intervention period. Non-targeted metabolomics of the feces was performed using ultra-performance liquid chromatography (UPLC)-Q-Exactive Orbitrap/mass spectrometer. Oral administration of B. longum CCFM1077 for six weeks significantly decreased the serum levels of TC (p

Wild rice (WLD) attenuated hyperglycemia, hyperlipidemia and chronic inflammation in mice receiving a high-fat diet (HFD) versus white rice (WHR), but the underlying mechanism is not well understood. We examined the influence of HFD + WLD on gut microbiota, short chain fatty acids (SCFAs) and the correlation with metabolic or inflammatory markers in mice versus HFD + WHR. C57BL/6J mice received HFD + 26 g weight (wt) % WHR or WLD or 13 g wt% WHR + 13 g wt% WLD (WTWD) for 12 weeks. Plasma levels of glucose, cholesterol and triglycerides, insulin resistance and inflammatory markers after overnight fasting were lower, and the abundances of fecal Lactobacillus gasseri and propionic acid were higher in HFD + WLD-fed mice than in HFD + WHR-fed mice. The anti-inflammatory effects of HFD + WTWD were weaker than HFD + WLD but were greater than those in HFD + WHR-fed mice. Abundances of fecal Lactobacillus gasseri and propionic acid in mice receiving HFD + WLD were higher than those in mice fed with HFD + WHR. The abundances of fecal L. gasseri and propionic acid negatively correlated with metabolic and inflammatory markers. The findings of the present study suggest that WLD attenuated metabolic and inflammatory disorders in mice on HFD. Interactions between WLD components and gut microbiota may upregulate fecal SCFAs, and the latter may be attributed to the benefits of WLD on metabolism and inflammation in mice on HFD.

Abstract Background Intestinal flora has been proposed to mediate the occurrence of postmenopausal osteoporosis (PMO). However, the mechanism by which microbes and their metabolites interactively promote PMO remains unknown. Methods This study aimed to investigate changes in the intestinal flora and associated metabolites, and their role in PMO. 16S rRNA gene sequencing and metabolomics were performed to obtain postmenopausal women with osteopenia (lower bone mass, LBM), postmenopausal women with osteoporosis (OST), and healthy women as the control group. Results We identified taxa-specific and metabolite differences in the intestinal flora of the participants of this study. The pathogenic bacteria Klebsiella (0.59% and 0.71%, respectively) and Escherichia-Shigella (2.72% and 4.30%, respectively) were enriched in the LBM and OST groups (p

Abstract Background Women suffer from various distress and disturbances after menopause, including osteoporosis, a risk factor associated with multiple diseases. Altered gut microbiota has been implicated in postmenopausal osteoporosis. In this study, to understand gut microbiota signatures and fecal metabolite changes in postmenopausal women with osteoporosis, 108 postmenopausal women were recruited for intestinal microbiota and fecal metabolite detection. Among these participants, 98 patients, who met the inclusion criteria, were divided into postmenopausal osteoporosis (PMO) and non-postmenopausal osteoporosis (non-PMO) groups based on bone mineral density (BMD). The compositions of gut bacteria and fungi were examined by 16 S rRNA gene sequencing and ITS sequencing, respectively. Meanwhile, fecal metabolites were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS). Results We found that bacterial α-diversity and β-diversity were significantly altered in PMO compared to non-PMO patients. Interestingly, fungi composition showed larger changes, and the differences in β-diversity were more significant between PMO and non-PMO patients. Metabolomics analysis revealed that fecal metabolites, such as levulinic acid, N-Acetylneuraminic acid, and the corresponding signaling pathways were also changed significantly, especially in the alpha-Linolenic acid metabolism and selenocompound metabolism. The screened differential bacteria, fungi, and metabolites closely correlated with clinical findings between these two groups, for example, the bacterial genus, Fusobacterium, the fungal genus, Devriesia, and the metabolite, L-pipecolic acid, were significantly associated with BMD. Conclusions Our findings indicated that there were remarkable changes in gut bacteria, fungi, and fecal metabolites in postmenopausal women, and such changes were notably correlated with patients’ BMD ​​and clinical findings. These correlations provide novel insights into the mechanism of PMO development, potential early diagnostic indicators, and new therapeutic approaches to improve bone health in postmenopausal women.

Naringin, a natural flavanone primarily found in citrus fruits, has garnered increased attention due to its recognized antioxidative, anti-inflammatory, and cardioprotective attributes. However, the functions of naringin in regulating energy expenditure are poorly understood. In the present study, we observed that twelve weeks of naringin supplementation substantially reshaped the metabolic profile of high-fat diet (HFD)-fed mice, by inhibiting body weight gain, reducing liver weight, and altering body compositions. Notably, naringin exhibited a remarkable capacity to augment whole-body energy expenditure of the tested mice by enhancing the thermogenic activity of brown adipose tissue (BAT) and stimulating browning of inguinal white adipose tissue (iWAT). Furthermore, our results showed naringin supplementation modified gut microbiota composition, specifically increasing the abundance of Bifidobacterium and Lachnospiraceae_bacterium_28-4, while reducing the abundance of Lachnospiraceae_bacterium_DW59 and Dubosiella_newyorkensis. Subsequently, we also found naringin supplementation altered fecal metabolite profile, by significantly promoting the production of taurine, tyrosol, and thymol, which act as potent activators of thermoregulation. Interestingly, the metabolic effects of naringin were abolished upon gut microbiota depletion through antibiotic intervention, concurrently leading the disappearance of naringin-induced thermogenesis and protective actions on diet-induced obesity. This discovery revealed a novel food-driven cross-sectional communication between gut bacteria and adipose tissues. Collectively, our data indicate that naringin supplementation stimulates BAT thermogenesis, alters fat distribution, promotes the browning process, and consequently inhibits body weight gain; importantly these metabolic effects require the participation of gut bacteria.

ABSTRACT In this study, the impact of traditional rice-based fermented alcoholic beverages (two types of Apong drink: Poro and Nogin) on the gut microbiome and health of the Mishing community in India was examined. Two groups (n = 71 in each group, 58 females and 84 males) that consumed one of these beverages were compared to a control group (n = 24, all males) that did not consume either beverage. Gut microbial composition was analyzed by sequencing 16S rRNA of fecal metagenomes and analyzing untargeted fecal metabolites, and short-chain fatty acids (SCFAs). We also collected data on anthropometric measures and serum biochemical markers. Our results showed that Apong drinkers had higher blood pressure, but lower blood glucose and total protein levels than other non-drinkers. Also, gut microbiome composition was found to be affected by the choice of Apong, with Apong drinkers having a more diverse and distinct microbiome compared to non-drinkers. Apong drink type or being a drinker or not explained even a higher variation of fecal metabolome composition than microbiome composition and Apong drinkers had lower levels of the SCFA isovaleric acid than non-drinkers. Overall, this study shows that a single dietary factor can significantly impact the gut microbiome of a community and highlights the potential role of traditional fermented beverages in modulating gut bacteria.IMPORTANCEOur study investigated how a traditional drink called Apong, made from fermented rice, affects the gut and health of the Mishing community in India. We compared two groups of people who drink Apong to a group of people who do not drink it. To accomplish this, we studied the gut bacteria, fecal metabolites, and blood samples of the participants. It was found that the people who drank Apong had higher blood pressure but lower blood sugar and protein levels than people who did not drink it. We also found that the gut microbiome composition of people who drank Apong was different from those who did not drink it. Moreover, people who drank Apong had lower levels of isovaleric acid in their feces. Overall, this study shows that a traditional drink like Apong can affect the gut bacteria of a community.

ObjectivesPeriodontitis is associated with benign prostatic hyperplasia (BPH), whether it related to gut floramicrobiota and metabonomics is unclear.MethodsWe established ligature-induced periodontitis (EP), testosterone-induced BPH, and composite rat models. Fecal samples were collected to detect gut microbiota by 16S rDNA sequencing and metabonomics were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS).ResultsSequencing results revealed differential gut floramicrobiota composition between EP+BPH group and other three groups. The abundances of Ruminococcus flavefaciens were significantly increased in EP+BPH group compared with other groups. Tenericutes, Mollicutes, RF39 and Ruminococcus gnavus were significantly decreased in EP+BPH group compared with BPH group, while Ruminococcus callidus and Escherichia were significantly decreased compared with EP group. For gut metabonomics, LC-MS/MS showed that fecal metabolites and seven metabolic pathways were changed in EP+BPH group, such as biosynthesis of unsaturated fatty acids, steroid hormone biosynthesis. Correlation analysis showed that the alterations of gut metabolism were significantly correlated with differential gut floramicrobiota, such as Ruminococcus callidus and Ruminococcus flavefaciens.ConclusionOur study highlights the relationship of periodontitis and BPH, the alterations of gut floramicrobiota and metabolites may be involved in two diseases, which provides new idea for prevention and treatment of patients with periodontitis concurrent BPH.

Allergic rhinitis (AR), as a recurrent allergic inflammatory disease, has an increasing inci- dence year by year in China, which seriously affects the work and life of patients. However, the pathogenesis of AR is still unclear, and the studies have found that intestinal flora and fecal metabolites can not only interact with each other, but both can participate in the occurrence and development of AR by affecting mucosal barrier function, regulating immunity, and so on, which may provide new possibilities for the treatment of AR. This paper reviewed the articles on the relationship between intestinal flora and related fecal metabolites and AR in recent years, in order to provide ideas for the treatment and pathogenesis of AR. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: 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. Results: The results showed that Ziyan green tea intervention improved depression-like behaviour, neurobiochemical factors, and reduced levels of proinflammatory 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). Discussion: 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. [ABSTRACT FROM AUTHOR]

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental condition with hallmark behavioral manifestations including impaired social communication and restricted repetitive behavior. In addition, many affected individuals display metabolic imbalances, immune dysregulation, gastrointestinal dysfunction, and altered gut microbiome compositions.MethodsWe sought to better understand nonbehavioral features of ASD by determining molecular signatures in peripheral tissues through mass spectrometry methods (ultrahigh performance liquid chromatography-tandem mass spectrometry) with broad panels of identified metabolites. Herein, we compared the global metabolome of 231 plasma and 97 fecal samples from a large cohort of children with ASD and typically developing control children.ResultsDifferences in amino acid, lipid, and xenobiotic metabolism distinguished ASD and typically developing samples. Our results implicated oxidative stress and mitochondrial dysfunction, hormone level elevations, lipid profile changes, and altered levels of phenolic microbial metabolites. We also revealed correlations between specific metabolite profiles and clinical behavior scores. Furthermore, a summary of metabolites modestly associated with gastrointestinal dysfunction in ASD is provided, and a pilot study of metabolites that can be transferred via fecal microbial transplant into mice is identified.ConclusionsThese findings support a connection between metabolism, gastrointestinal physiology, and complex behavioral traits and may advance discovery and development of molecular biomarkers for ASD.

Abstract Background There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention. Methods We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism. Results After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P = 0.048), insulin (P = 0.005), and HbA1c levels (P = 0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P = 0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations. Conclusions Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management. Trial registration The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).

In this study, we investigated the correlation between the composition and function of the gut microbiota and the semen quality of Rongchang boars. Significant differences in gut microbial composition between boars with high (group H) and low (group L) semen utilization rates were identified through 16S rRNA gene sequencing, with 18 differential microbes observed at the genus level. Boars with lower semen utilization rates exhibited a higher relative abundance of Treponema, suggesting its potential role in reducing semen quality. Conversely, boars with higher semen utilization rates showed increased relative abundances of Terrisporobacter, Turicibacter, Stenotrophomonas, Clostridium sensu stricto 3, and Bifidobacterium, with Stenotrophomonas and Clostridium sensu stricto 3 showing a significant positive correlation with semen utilization rates. The metabolomic analyses revealed higher levels of gluconolactone, D-ribose, and 4-pyridoxic acid in the H group, with 4 pyridoxic acid and D-ribose showing a significant positive correlation with Terrisporobacter and Clostridium sensu stricto 3, respectively. In contrast, the L group showed elevated levels of D-erythrose-4-phosphate, which correlated negatively with Bifidobacterium and Clostridium sensu stricto 3. These differential metabolites were enriched in the pentose phosphate pathway, vitamin B6 metabolism, and antifolate resistance, potentially influencing semen quality. These findings provide new insights into the complex interplay between the gut microbiota and boar reproductive health and may offer important information for the discovery of disease biomarkers and reproductive health management.

The current trend of dog owners increasingly favoring the functional value of food to assure preventive health and wellbeing of their pets has been raising the interest in microalgae as natural additives with bioactive properties. However, scientific studies addressing the effects of microalgae supplementation in diets for dogs are scarce. This study aimed to evaluate the effects of dietary supplementation with three microalgae species (Chlorella vulgaris, Nannochloropsis oceanica, and Tetradesmus obliquus) on diet palatability, total tract digestibility, metabolizable energy content, fecal metabolites and microbiota of dogs. Twelve adult Beagle dogs were used in three two-bowl tests to compare the palatability of a commercial complete diet for adult dogs without (reference diet) and with 1.5% supplementation of each microalgae. From the results obtained, three digestibility trials were performed according to a replicated Latin square 3 × 3, with six adult Beagle dogs, three experimental periods of 10 days each, and three dietary supplementation levels of microalgae (0.5, 1.0, and 1.5%). In each trial, effects of microalgae supplementation levels on total tract digestibility, metabolizable energy content, fecal metabolites and microbiota of dogs were evaluated. First diet approached or tasted was not significantly affected by microalgae inclusion, but dogs showed a preference for the reference diet over the diets with 1.5% inclusion of C. vulgaris and N. oceanica, no difference being observed with 1.5% T. obliquus. In all digestibility trials, dietary supplementation with microalgae up to 1.5% did not greatly affected the dietary chemical composition and kept unaffected food intake, fecal output and metabolites, and digestibility of nutrients and energy. Compared with the reference diet, supplementation with C. vulgaris increased protein digestibility. Fecal characteristics and metabolites were affected by microalgae supplementation, being the effects dependent on the species. Fecal microbiota composition of dogs fed with microalgae-supplemented diets was modified by promoting the beneficial Turicibacter and Peptococcus genera associated with gut health and activation of the immune system. Overall, the results support C. vulgaris, N. oceanica, and T. obliquus as sustainable functional supplements that potentially enhance gastrointestinal health of dogs through the selective stimulation of microbiota without detrimental effects on food intake and digestibility.

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. [ABSTRACT FROM AUTHOR]

Background: Intestinal flora has been proposed to mediate the occurrence of postmenopausal osteoporosis (PMO). However, the mechanism by which microbes and their metabolites interactively promote PMO remains unknown. Methods: This study aimed to investigate changes in the intestinal flora and associated metabolites, and their role in PMO. 16S rRNA gene sequencing and metabolomics were performed to obtain postmenopausal women with osteopenia (lower bone mass, LBM), postmenopausal women with osteoporosis (OST), and healthy women as the control group. Results: We identified taxa-specific and metabolite differences in the intestinal flora of the participants of this study. The pathogenic bacteria Klebsiella (0.59% and 0.71%, respectively) and Escherichia-Shigella (2.72% and 4.30%, respectively) were enriched in the LBM and OST groups (p < 0.05). Some short-chain fatty acid (SCFAs) producing bacteria, Lactobacillus, Akkermansia, Prevotella, Alistipes, and Butyricicoccus, were reduced in patients with LBM and OST compared to the control. Moreover, fecal metabolomic analyses suggested that the metabolites of indole-3-acetic acid and 7-ketodeoxycholic acid were altered in the LBM and OST groups compared to the control (p < 0.05). Enrichment analysis suggested that valine, leucine, and isoleucine biosynthesis; aromatic amino acid biosynthesis; and phenylalanine metabolism were significantly associated with the identified microbiota biomarkers and OST. Moreover, metabolite marker signatures distinguished patients in the OST from those in the control group with an area under the curve (AUC) of 0.978 and 1.00 in the negative and positive ion modes, respectively. Finally, we also found that the fecal level of interleukin-10 (IL-10) in the OST group was significantly lower than that in the control group and LBM group (p < 0.05), while tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were significantly higher in the OST group than that in the control group (p < 0.05). Conclusions: This study provides robust evidence connecting the intestinal flora and fecal metabolomics with PMO. Integrated metabolite and microbiota analyses demonstrated that in addition to dysregulated bacteria, indole-3-acetic acid, 7-ketodeoxycholic acid, and other metabolites can be used for the distinguish of LBM and PMO. [ABSTRACT FROM AUTHOR]

Background: Women suffer from various distress and disturbances after menopause, including osteoporosis, a risk factor associated with multiple diseases. Altered gut microbiota has been implicated in postmenopausal osteoporosis. In this study, to understand gut microbiota signatures and fecal metabolite changes in postmenopausal women with osteoporosis, 108 postmenopausal women were recruited for intestinal microbiota and fecal metabolite detection. Among these participants, 98 patients, who met the inclusion criteria, were divided into postmenopausal osteoporosis (PMO) and non-postmenopausal osteoporosis (non-PMO) groups based on bone mineral density (BMD). The compositions of gut bacteria and fungi were examined by 16 S rRNA gene sequencing and ITS sequencing, respectively. Meanwhile, fecal metabolites were analyzed using liquid chromatography coupled with mass spectrometry (LC-MS). Results: We found that bacterial α-diversity and β-diversity were significantly altered in PMO compared to non-PMO patients. Interestingly, fungi composition showed larger changes, and the differences in β-diversity were more significant between PMO and non-PMO patients. Metabolomics analysis revealed that fecal metabolites, such as levulinic acid, N-Acetylneuraminic acid, and the corresponding signaling pathways were also changed significantly, especially in the alpha-Linolenic acid metabolism and selenocompound metabolism. The screened differential bacteria, fungi, and metabolites closely correlated with clinical findings between these two groups, for example, the bacterial genus, Fusobacterium, the fungal genus, Devriesia, and the metabolite, L-pipecolic acid, were significantly associated with BMD. Conclusions: Our findings indicated that there were remarkable changes in gut bacteria, fungi, and fecal metabolites in postmenopausal women, and such changes were notably correlated with patients' BMD ​​and clinical findings. These correlations provide novel insights into the mechanism of PMO development, potential early diagnostic indicators, and new therapeutic approaches to improve bone health in postmenopausal women. [ABSTRACT FROM AUTHOR]

Disturbances in the gut microbiota and its derived metabolites are closely related to the occurrence and development of hepatic steatosis. The white kidney bean (WKB), as an excellent source of protein, dietary fiber, and phytochemicals, has recently received widespread attention and might exhibit beneficial effects on a high-fat diet (HFD)-induced hepatic steatosis via targeting gut microbiota and its metabolites. The results indicated that HFD, when supplemented with WKB for 12 weeks, could potently reduce obesity symptoms, serum lipid profiles, and glucose, as well as improve the insulin resistance and liver function markers in mice, thereby alleviating hepatic steatosis. An integrated fecal microbiome and metabolomics analysis further demonstrated that WKB was able to normalize HFD-induced gut dysbiosis in mice, thereby mediating the alterations of a wide range of metabolites. Particularly, WKB remarkably increased the relative abundance of probiotics (Akkermansiaceae, Bifidobacteriaceae, and norank_f_Muribaculaceae) and inhibited the growth of hazardous bacteria (Mucispirillum, Enterorhabdus, and Dubosiella) in diet-induced hepatic steatosis mice. Moreover, the significant differential metabolites altered by WKB were annotated in lipid metabolism, which could ameliorate hepatic steatosis via regulating glycerophospholipid metabolism. This study elucidated the role of WKB from the perspective of microbiome and metabolomics in preventing nonalcoholic fatty liver disease, which provides new insights for its application in functional foods. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are widely used in the treatment of immune-mediated diseases due to their anti-inflammatory and immunosuppressive effects. Prednisone is one of the most commonly used GCs. However, it is still unknown whether prednisone affects gut fungi in rats. Herein we investigated whether prednisone changed the composition of gut fungi and the interactions between gut mycobiome and bacteriome/fecal metabolome in rats. Twelve male Sprague-Dawley rats were randomly assigned to a control group and a prednisone group which received prednisone daily by gavage for 6 weeks. ITS2 rRNA gene sequencing of fecal samples was performed to identify differentially abundant gut fungi. The associations between gut mycobiome and bacterial genera/fecal metabolites obtained from our previously published study were explored by using Spearman correlation analysis. Our data showed that there were no changes in the richness of gut mycobiome in rats after prednisone treatment, but the diversity increased significantly. The relative abundance of genera Triangularia and Ciliophora decreased significantly. At the species level, the relative abundance of Aspergillus glabripes increased significantly, while Triangularia mangenotii and Ciliophora sp. decreased. In addition, prednisone altered the gut fungi-bacteria interkingdom interactions in rats after prednisone treatment. Additionally, the genus Triangularia was negatively correlated with m-aminobenzoic acid, but positively correlated with hydrocinnamic acid and valeric acid. Ciliophora was negatively correlated with phenylalanine and homovanillic acid, but positively correlated with 2-Phenylpropionate, hydrocinnamic acid, propionic acid, valeric acid, isobutyric acid, and isovaleric acid. In conclusion, long-term prednisone treatment caused fungal microbiota dysbiosis and might alter the ecological interaction between gut mycobiome and bacteriome in rats. [ABSTRACT FROM AUTHOR]

(1) Background: Piglet diarrhea is one of the most serious diseases in pigs and has brought great economic losses to the pig industry. Alteration of the gut microbiota is an important factor in the etiology of piglet diarrhea. Therefore, this study aimed to analyze the differences in the gut microbial structures and fecal metabolic profile between post-weaning diarrhea and healthy Chinese Wannan Black pigs. (2) Methods: An integrated approach of 16S rRNA gene sequencing combined with LC/MS-based metabolomics was employed in this study. (3) Results: We found an increase in the relative abundance of the bacterial genus Campylobacter and a decrease in phylum Bacteroidetes and the species Streptococcus gallolyticus subsp. macedonicus. (S. macedonicus) in piglet diarrhea. Meanwhile, obvious changes in the fecal metabolic profile of diarrheic piglets were also detected, particularly higher levels of polyamines (spermine and spermidine). Moreover, there were substantial associations between the disturbed gut microbiota and the altered fecal metabolites, especially a strong positive relationship between spermidine and Campylobacter. (4) Conclusions: These observations may provide novel insights into potential etiologies related to post-weaning diarrhea and further enhance our understanding of the role of gut microbiota in host homeostasis and in modulating gut microbial structure. [ABSTRACT FROM AUTHOR]

A large number of studies have shown that propolis has positive effects in the treatment of type 2 diabetes mellitus (T2DM). However, there are have only been a few reports that are based on an ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) analysis of the fecal metabolomics of ethanol extract of propolis (EEP) in the treatment of T2DM. The present investigation was designed to screen potential biomarkers of T2DM by the metabonomic method and to explain the possible anti-diabetes mechanism of EEP according to the changes in the biomarkers. The results showed that EEP improved the body weight (BW) of T2DM mice, lowered blood sugar levels, and significantly restored blood biochemical indicators related to T2DM, such as fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), aspartate transaminase (AST), and alanine aminotransferase (ALT). Liver pathology showed that EEP reversed liver damage caused by T2DM. Metabolomics data identified 27 potential biomarkers in fecal samples. EEP effectively regulated the dysfunction in the metabolic pathways of glycerophospholipids, sphingolipids, riboflavins, and sterol lipids caused by T2DM. In summary, our research results revealed positive effects of EEP in the treatment of T2DM and provided potential candidate markers for further research and in the clinical treatment of T2DM.

Abstract Background Antibody-mediated rejection (AMR) remains one of the major barriers for graft survival after kidney transplantation. Our previous study suggested a gut microbiota dysbiosis in kidney transplantation recipients with AMR. However, alternations in gut microbial function and structure at species level have not been identified. In the present study, we investigated the metagenomic and metabolic patterns of gut microbiota in AMR patients to provide a comprehensive and in-depth understanding of gut microbiota dysbiosis in AMR. Methods We enrolled 60 kidney transplantation recipients, 28 showed AMR and 32 were non-AMR controls with stable post-transplant renal functions. Shotgun sequencing and untargeted LC/MS metabolomic profiling of fecal samples were performed in kidney transplantation recipients with AMR and controls. Results Totally, we identified 311 down-regulated and 27 up-regulated gut microbial species associated with AMR after kidney transplantation, resulting in the altered expression levels of 437 genes enriched in 22 pathways, of which 13 were related to metabolism. Moreover, 32 differential fecal metabolites were found in recipients with AMR. Among them, alterations in 3b-hydroxy-5-cholenoic acid, l-pipecolic acid, taurocholate, and 6k-PGF1alpha-d4 directly correlated with changes in gut microbial species and functions. Specific differential fecal species and metabolites were strongly associated with clinical indexes (Cr, BUN, etc.), and could distinguish the recipients with AMR from controls as potential biomarkers. Conclusions Altogether, our findings provided a comprehensive and in-depth understanding of the correlation between AMR and gut microbiota, which is important for the etiological and diagnostic study of AMR after kidney transplantation.

Background: There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention. Methods: We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism. Results: After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P = 0.048), insulin (P = 0.005), and HbA1c levels (P = 0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P = 0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations. Conclusions: Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management. Trial registration: The study was registered at https://www.chictr.org.cn (ChiCTR1800019663). [ABSTRACT FROM AUTHOR]

Background: Therapeutic targets for ulcerative colitis (UC) and prediction models of antitumor necrosis factor (TNF) therapy outcomes have not been fully reported. Objective: Investigate the characteristic metabolite and lipid profiles of fecal samples of UC patients before and after adalimumab treatment and develop a prediction model of clinical remission following adalimumab treatment. Design: Prospective, observational, multicenter study was conducted on moderate-to-severe UC patients (n = 116). Methods: Fecal samples were collected from UC patients at 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n = 37). Clinical remission was assessed using the Mayo score. Metabolomic and lipidomic analyses were performed using gas chromatography mass spectrometry and nano electrospray ionization mass spectrometry, respectively. Orthogonal partial least squares discriminant analysis was performed to establish a remission prediction model. Results: Fecal metabolites in UC patients markedly differed from those in HC at baseline and were changed similarly to those in HC during treatment; however, lipid profiles did not show these patterns. After treatment, the fecal characteristics of remitters (RM) were closer to those of HC than to those of non-remitters (NRM). At 8 and 56 weeks, amino acid levels in RM were lower than those in NRM and similar to those in HC. After 56 weeks, levels of 3-hydroxybutyrate, lysine, and phenethylamine decreased, and dodecanoate level increased in RM similarly to those in HC. The prediction model of long-term remission in male patients based on lipid biomarkers showed a higher performance than clinical markers. Conclusion: Fecal metabolites in UC patients markedly differ from those in HC, and the levels in RM are changed similarly to those in HC after anti-TNF therapy. Moreover, 3-hydroxybutyrate, lysine, phenethylamine, and dodecanoate are suggested as potential therapeutic targets for UC. A prediction model of long-term remission based on lipid biomarkers may help implement personalized treatment. [ABSTRACT FROM AUTHOR]

High-fat diets (HFD) can promote the development of hepatic steatosis by altering the structure and composition of gut flora. In this study, the potential therapeutic mechanism of Lycium barbarum oligosaccharide (LBO) against hepatic steatosis was investigated by analyzing the changes in the intestinal flora and metabolites in mice. Mice on an HFD were administered LBO by gavage once daily for a continuous period of eight weeks. Compared with the HFD group, the levels of triglyceride (TG), alanine aminotransferase (ALT) in the serum, and hepatic TG were significantly reduced in the LBO group, and liver lipid accumulation was obviously improved. In addition, LBO could regulate the HFD-induced alteration of intestinal flora. The HFD increased the proportion of Barnesiellaceae, Barnesiella, and CHKCI001. LBO increased the proportion of Dubosiella, Eubacterium, and Lactobacillus. LBO also altered the fecal metabolic profile. Significantly different metabolites between LBO and the HFD, such as taurochenodeoxycholate, taurocholate, fluvastatin, and kynurenic acid, were related to the cholesterol metabolism, bile acid metabolism, and tryptophan metabolic pathways. In light of the above, LBO can alleviate HFD-induced NAFLD by modulating the components of the intestinal flora and fecal metabolites. [ABSTRACT FROM AUTHOR]

Background: Compatible pair housing of macaques in research settings increases species‐typical behaviors and facilitates beneficial social buffering. It is not yet established whether these benefits are maintained after intrafacility transfer and domestic quarantine, which are two stressors that can lead to behavioral and clinical abnormalities. Methods: We evaluated 40 adolescent male rhesus macaques who were single‐ or pair‐housed immediately following an intrafacility transfer. We measured behavior, fecal cortisol, body weight, and diarrhea occurrence. Body weight and diarrhea occurrence were also retrospectively analyzed in an additional 120 adolescent rhesus who underwent a similar transfer. Results and Conclusions: Pair‐housed macaques exhibited less of some undesirable behaviors (e.g., self‐clasping) and experienced less diarrhea than single‐housed subjects; however, no significant differences in cortisol levels or alopecia measures were found. The demonstrated beneficial effects of pair housing for rhesus macaques following intrafacility transfer and adjustment suggest pairing upon arrival at a new facility will bolster animal welfare. [ABSTRACT FROM AUTHOR]

Recently, cognitive impairments (CI) and behavioral abnormalities in patients with amyotrophic lateral sclerosis (ALS) have been reported. However, the underlying mechanisms have been poorly understood. In the current study, we explored the role of gut microbiota in CI of ALS patients. We collected fecal samples from 35 ALS patients and 35 healthy controls. The cognitive function of the ALS patients was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen. We analyzed these samples by using 16S rRNA gene sequencing as well as both untargeted and targeted (bile acids) metabolite mapping between patients with CI and patients with normal cognition (CN). We found altered gut microbial communities and a lower ratio of Firmicutes/ Bacteroidetes in the CI group, compared with the CN group. In addition, the untargeted metabolite mapping revealed that 26 and 17 metabolites significantly increased and decreased, respectively, in the CI group, compared with the CN group. These metabolites were mapped to the metabolic pathways associated with bile acids. We further found that cholic acid and chenodeoxycholic acid were significantly lower in the CI group than in the CN group. In conclusion, we found that the gut microbiota and its metabolome profile differed between ALS patients with and without CI and that the altered bile acid profile in fecal samples was significantly associated with CI in ALS patients. These results need to be replicated in larger studies in the future. [ABSTRACT FROM AUTHOR]

Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn’s disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGFβ superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and/or perpetuation of inflammation in CD.

Abstract Background Diet has a large influence on gut microbiota diversity and function. Although previous studies have investigated the effect of dietary interventions on the gut microbiome, longitudinal changes in the gut microbiome, microbial functions, and metabolite profiles post dietary interventions have been underexplored. How long these outcomes require to reach a steady-state, how they relate to one another, and their impact on host physiological changes are largely unknown. To address these unknowns, we collected longitudinal fecal samples following an abrupt dietary change in healthy adult beagles (n = 12, age: 5.16 ± 0.87 year, BW: 13.37 ± 0.68 kg) using a crossover design. All dogs were fed a kibble diet (control) from d1-14, and then fed that same diet supplemented with fiber (HFD) or a protein-rich canned diet (CD) from d15-27. Fresh fecal samples were collected on d13, 16, 20, 24, and 27 for metabolite and microbiome assessment. Fecal microbial diversity and composition, metabolite profiles, and microbial functions dramatically diverged and stabilized within a few days (2 d for metabolites; 6 d for microbiota) after dietary interventions. Fecal acetate, propionate, and total short-chain fatty acids increased after change to HFD, while fecal isobutyrate, isovalerate, total branched-chain fatty acids, phenol, and indole increased after dogs consumed CD. Relative abundance of ~ 100 bacterial species mainly belonging to the Firmicutes, Proteobacteria, and Actinobacteria phyla increased in HFD. These shifts in gut microbiome diversity and composition were accompanied by functional changes. Transition to HFD led to increases in the relative abundance of KEGG orthology (KO) terms related to starch and sucrose metabolism, fatty acid biosynthesis, and amino sugar and nucleotide sugar metabolism, while transition to CD resulted in increased relative abundance of KO terms pertaining to inositol phosphate metabolism and sulfur metabolism. Significant associations among fecal microbial taxa, KO terms, and metabolites were observed, allowing for high-accuracy prediction of diet group by random forest analysis. Conclusions Longitudinal sampling and a multi-modal approach to characterizing the gastrointestinal environment allowed us to demonstrate how drastically and quickly dietary changes impact the fecal microbiome and metabolite profiles of dogs following an abrupt dietary change and identify key microbe-metabolite relationships that allowed for treatment prediction.

IntroductionThe fecal metabolome provides insight into overall gastrointestinal and microbial health. Methods for fecal sample storage in metabolomics research vary, however, making comparisons within current literature difficult. This study investigated the effect of ambient temperature exposure on microbial-derived metabolites of feline fecal samples.MethodsFecal samples were collected from 11 healthy cats from a local boarding facility. Samples were manually homogenized and aliquoted. The first aliquot was frozen at -80°C within 1 hour of defecation, and remaining samples were exposed to ambient temperature for 2, 4, 6, 8, 12, and 24 h prior to freezing at -80°C. Fecal metabolites were quantified using 1H NMR spectroscopy. Fifty metabolites were grouped into six categories (27 amino acids, 8 fatty acids, 5 sugars, 3 alcohols, 2 nitrogenous bases, 5 miscellaneous).ResultsConcentrations of 20 out of 50 metabolites significantly differed due to ambient temperature exposure (7 amino acids, 6 fatty acids, 2 alcohols, 1 nitrogenous base, 4 miscellaneous). The earliest detected changes occurred 6 h post-defecation for cadaverine and fumaric acid.DiscussionThis study shows ambient temperature exposure alters the composition of the feline fecal metabolome, but short-term (up to 4 h) exposure prior to storage in the freezer seems to be acceptable.

Purpose: Gut microbiota dysbiosis, a core pathophysiology of irritable bowel syndrome (IBS), is closely related to immunological and metabolic functions. Gut microbiota-based therapeutics have been recently explored in several studies. Bifico is a probiotic cocktail widely used in gastrointestinal disorders which relate to the imbalance of gut microbiota. However, the efficacy and potential mechanisms of Bifico treatment in IBS remains incompletely understood. Methods: Adopting a wrap restraint stress (WRS) -induced IBS mice model. Protective effect of Bifico in IBS mice was examined through abdominal withdrawal reflex (AWR) scores. 16S rDNA, 1H nuclear magnetic resonance (1H-NMR) and western blot assays were performed to analyze alterations of gut microbiota, microbiome metabolites and inflammatory cytokines, respectively. Results: Bifico could decrease intestinal visceral hypersensitivity. Although gut microbiota diversity did not increase, composition of gut microbiota was changed after treatment of Bifico, which were characterized by an increase of Proteobacteria phylum and Actinobacteria phylum, Muribaculum genus, Bifidobacterium genus and a decrease of Parabacteroides genus, Sutterella genus and Lactobacillus genus. Moreover, Bifico elevated the concentration of short-chain fatty acids (SCFAs) and reduced protein levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). From further Spearman's correlation analysis, Bifidobacterium genus were positively correlated with SCFAs including propionate, butyrate, valerate and negatively correlated with IL-6 and TNF-α. Conclusion: Bifico could alleviate symptoms of IBS mice through regulation of the gut microbiota, elevating production of SCFAs and reducing the colonic inflammatory response. [ABSTRACT FROM AUTHOR]

Maternal gut microbiota is an important regulator for the metabolism and immunity of the fetus during pregnancy. Recent studies have indicated that maternal intestinal microbiota is closely linked to the development of fetus and infant health. Some bacterial metabolites are considered to be directly involved in immunoregulation of fetus during pregnancy. However, the detailed mechanisms are largely unknown. In this study, we exploited the potential correlation between the gut microbiota of pregnant sows and the occurrence of stillborn piglets by combining the 16S rRNA gene and metagenomic sequencing data, and fecal metabolome in different cohorts. The results showed that several bacterial species from Bacteroides, potential pathogens, and LPS-producing bacteria exhibited significantly higher abundances in the gut of sows giving birth to stillborn piglets. Especially, Bacteroides fragilis stood out as the key driver in both tested cohorts and showed the most significant association with the occurrence of stillborn piglets in the DN1 cohort. However, several species producing short-chain fatty acids (SCFAs), such as Prevotella copri, Clostridium butyricum and Faecalibacterium prausnitzii were enriched in the gut of normal sows. Functional capacity analysis of gut microbiome revealed that the pathways associated with infectious diseases and immune diseases were enriched in sows giving birth to stillborn piglets. However, energy metabolism had higher abundance in normal sows. Fecal metabolome profiling analysis found that Lysophosphatidylethanolamine and phosphatidylethanolamine which are the main components of cell membrane of Gram-negative bacteria showed significantly higher concentration in stillbirth sows, while SCFAs had higher concentration in normal sows. These metabolites were significantly associated with the stillborn-associated bacterial species including Bacteroides fragilis. Lipopolysaccharide (LPS), IL-1β, IL-6, FABP2, and zonulin had higher concentration in the serum of stillbirth sows, indicating increased intestinal permeability and pro-inflammatory response. The results from this study suggested that certain sow gut bacterial species in late trimester of pregnancy, e.g., an excess abundance of Bacteroides fragilis, produced high concentration of LPS which induced sow pro-inflammatory response and might cause the death of the relatively weak piglets in a farrow. This study provided novel evidences about the effect of maternal gut microbiota on the fetus development and health. [ABSTRACT FROM AUTHOR]

Background: Growing evidence suggests the gut microbiota and metabolites in serum or fecal may play a key role in the process of alcohol use disorder (AUD). However, the correlations of gut microbiota and metabolites in both feces and serum in AUD subjects are not well understood. Methods: We established a rat model of AUD by a chronic intermittent ethanol voluntary drinking procedure, then the AUD syndromes, the gut microbiota, metabolomic profiling in feces and serum of the rats were examined, and correlations between gut microbiota and metabolites were analyzed. Results: Ethanol intake preference increased and maintained at a high level in experimental rats. Anxiety-like behaviors was observed by open field test and elevated plus maze test after ethanol withdraw, indicating that the AUD rat model was successfully developed. The full length 16S rRNA gene sequencing showed AUD significantly changed the β-diversity of gut microbial communities, and significantly decreased the microbial diversity but did not distinctly impact the microbial richness. Microbiota composition significantly changed in AUD rats, such as the abundance of Romboutsia and Turicibacter were significantly increased, whereas uncultured_bacterium_o_Mollicutes_ RF39 was decreased. In addition, the untargeted metabolome analysis revealed that many metabolites in both feces and serum were altered in the AUD rats, especially involved in sphingolipid metabolism and glycerophospholipid metabolism pathways. Finally, multiple correlations among AUD behavior, gut microbiota and co-changed metabolites were identified, and the metabolites were directly correlated with the gut microbiota and alcohol preference. Conclusion: The altered metabolites in feces and serum are important links between the gut microbiota dysbiosis and alcohol preference in AUD rats, and the altered gut microbiota and metabolites can be potentially new targets for treating AUD. [ABSTRACT FROM AUTHOR]