Glucosinolate extract from radish (Raphanus sativus L.) seed attenuates high-fat diet-induced obesity: insights into gut microbiota and fecal metabolites.

Background: Radish seed is a functional food with many beneficial health effects. Glucosinolates are characteristic components in radish seed that can be transformed into bioactive isothiocyanates by gut microbiota. Objective: The present study aims to assess anti-obesity efficacy of radish seed glucosinolates (RSGs) and explored the underlying mechanisms with a focus on gut microbiota and fecal metabolome. Methods: High-fat diet-induced obese mice were supplemented with different doses of RSGs extract for 8 weeks. Changes in body weight, serum lipid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels; and pathological changes in the liver and adipose tissue were examined. Fecal metabolome and 16S rRNA gene sequencing were used to analyze alterations in fecal metabolite abundance and the gut microbiota, respectively. Results and conclusion: Results showed that RSG extract prevented weight gain and decreased serum lipid, ALT, AST levels and lipid deposition in liver and epididymal adipocytes in obese mice. Treatment with RSG extract also increased gut microbiota diversity and altered the dominant bacteria genera in the gut microbiota, decreasing the abundance of Faecalibaculum and increasing the abundance of Allobaculum, Romboutsia, Turicibacter, and Akkermansia. Fecal metabolome results identified 570 differentially abundant metabolites, of which glucosinolate degradation products, such as sulforaphene and 7-methylsulfinylheptyl isothiocyanate, were significantly upregulated after RSG extract intervention. Furthermore, enrichment analysis of metabolic pathways showed that the anti-obesity effects of RSG extract may be mediated by alterations in bile secretion, fat digestion and absorption, and biosynthesis of plant secondary metabolites. Overall, RSG extract can inhibit the development of obesity, and the obesity-alleviating effects of RSG are related to alternative regulation of the gut microbiota and glucosinolate metabolites.

Licorice Extract Supplementation Benefits Growth Performance, Blood Biochemistry and Hormones, Immune Antioxidant Status, Hindgut Fecal Microbial Community, and Metabolism in Beef Cattle.

This study aimed to evaluate the effects of licorice extract (LE) on growth performance, nutrient apparent digestibility, serum index (biochemistry, hormones, humoral immunity, and antioxidant function), hindgut fecal microbiota, and metabolism in beef cattle. In total, 12 male yellow cattle aged 12 months were divided into two groups (6 cattle per group): the basal diet (CK group) and the basal diet supplemented with 2 g/kg LE (CHM group). The entire experimental phase lasted for 120 days, including a 30-day pre-feeding period. Compared to the CK group, the average daily gain, crude fiber, calcium, and crude protein nutrient digestibility were greater on d 30 than d 60 (p < 0.05) and the feed meat ratio was lower for LE addition (p < 0.01). In terms of serum indexes, the insulin and nitric oxide contents were enhanced on d 30, the alkaline phosphatase level was improved on d 60, and the levels of albumin, immunoglobulin A, and catalase were increased on d 90 (p < 0.05). In contrast, the cholesterol content was lower on d 60 for LE addition compared with the CK group (p < 0.05). The higher enrichment of [Eubacterium]-oxidoreducens-group, p-2534-18b5-gut-group, and Ileibacterium were observed in the CHM group (p < 0.05), while the relative abundances of Gallibacterium and Breznakia in the CHM group were lower compared with the CK group (p < 0.05). In addition, the differential metabolites related to healthy growth in the CHM group were increased compared with the CK group. And there was a close correlation between hindgut microbiota and metabolic differentials. In general, LE has a promoting effect on the growth performance and health status of beef cattle over a period (30 to 60 days).

Idiosyncratic Drug-Induced Liver Injury and Amoxicillin-Clavulanate: Spotlight on Gut Microbiota, Fecal Metabolome and Bile Acid Profile in Patients.

Several hepatic disorders are influenced by gut microbiota, but its role in idiosyncratic drug-induced liver injury (iDILI), whose main causative agent is amoxicillin-clavulanate, remains unknown. This pioneering study aims to unravel particular patterns of gut microbiota composition and associated metabolites in iDILI and iDILI patients by amoxicillin-clavulanate (iDILI-AC). Thus, serum and fecal samples from 46 patients were divided into three study groups: healthy controls (n = 10), non-iDILI acute hepatitis (n = 12) and iDILI patients (n = 24). To evaluate the amoxicillin-clavulanate effect, iDILI patients were separated into two subgroups: iDILI non-caused by amoxicillin-clavulanate (iDILI-nonAC) (n = 18) and iDILI-AC patients (n = 6). Gut microbiota composition and fecal metabolome plus serum and fecal bile acid (BA) analyses were performed, along with correlation analyses. iDILI patients presented a particular microbiome profile associated with reduced fecal secondary BAs and fecal metabolites linked to lower inflammation, such as dodecanedioic acid and pyridoxamine. Moreover, certain taxa like Barnesiella, Clostridia UCG-014 and Eubacterium spp. correlated with significant metabolites and BAs. Additionally, comparisons between iDILI-nonAC and iDILI-AC groups unraveled unique features associated with iDILI when caused by amoxicillin-clavulanate. In conclusion, specific gut microbiota profiles in iDILI and iDILI-AC patients were associated with particular metabolic and BA status, which could affect disease onset and progression.

Fecal metagenomic and metabolomic analyses reveal non-invasive biomarkers of Flavobacterium psychrophilum infection in ayu (Plecoglossus altivelis).

With the rapid growth of inland aquaculture worldwide, side effects such as the discharge of nutrients and antibiotics pose a threat to the global environments. A sustainable future for aquaculture requires an effective management system, including the early detection of disease through the monitoring of specific biomarkers in aquaculture tanks. To this end, we investigated whether fish feces in aquaculture tanks could be used for non-invasive health monitoring using ayu (Plecoglossus altivelis) infected with Flavobacterium psychrophilum, which causes bacterial cold-water disease worldwide. Feces that were subsequently produced in the tanks were used for metagenomic and metabolomic analyses. The relative abundances of the genera Cypionkella (0.6% ± 1.0%, 0.1% ± 0.2%), Klebsiella (11.2% ± 10.0%, 6.2% ± 5.9%), and F. psychrophilum (0.5% ± 1.0%, 0.0% ± 0.0%) were significantly higher in the feces of the infection challenge test tanks than in those of the control tanks. The abundances of cortisol, glucose, and acetate in the feces of the infection challenge test tanks were 2.4, 2.4, and 1.3 times higher, respectively, than those of the control tanks. Metagenome analysis suggested that acetate was produced by microbes such as Cypionkella. The abundances of indicated microbes or metabolites increased after day 4 of infection at the earliest, and were thus considered possible biomarkers. Our results suggest that feces produced in aquaculture tanks can potentially be used for non-invasive and holistic monitoring of fish diseases in aquaculture systems. IMPORTANCE: The aquaculture industry is rapidly growing, yet sustainability remains a challenge. One crucial task is to reduce losses due to diseases. Monitoring fish health and detecting diseases early are key to establishing sustainable aquaculture. Using metagenomic and metabolomic analyses, we found that feces of ayu infected with Flavobacterium psychrophilum contain various specific biomarkers that increased 4 days post-challenge, at the earliest. Our findings are the first step in establishing a novel, non-invasive, and holistic monitoring method for fish diseases in aquaculture systems, especially in ayu, which is an important freshwater fish species in Asia, promoting a sustainable future.

Novel probiotic preparation with in vivo gluten-degrading activity and potential modulatory effects on the gut microbiota.

Gluten possesses unique properties that render it only partially digestible. Consequently, it exerts detrimental effects on a part of the worldwide population who are afflicted with celiac disease (1%) or related disorders (5%), particularly due to the potential for cross-contamination even when adhering to a gluten-free diet (GFD). Finding solutions to break down gluten during digestion has a high nutritional and social impact. Here, a randomized double-blind placebo-controlled in vivo challenge investigated the gluten-degrading activity of a novel probiotic preparation comprising lactobacilli and their cytoplasmic extracts, Bacillus sp., and bacterial protease. In our clinical trial, we collected feces from 70 healthy volunteers at specific time intervals. Probiotic/placebo administration lasted 32 days, followed by 10 days of wash-out. After preliminary GFD to eliminate residual gluten from feces, increasing amounts of gluten (50 mg-10 g) were administered, each one for 4 consecutive days. Compared to placebo, the feces of volunteers fed with probiotics showed much lower amounts of residual gluten, mainly with increased intakes. Probiotics also regulate the intestinal microbial communities, improving the abundance of genera pivotal to maintaining homeostasis. Quantitative PCR confirmed that all probiotics persisted during the intervention, some also during wash-out. Probiotics promoted a fecal metabolome with potential immunomodulating activity, mainly related to derivatives of branched-chain amino acids and short-chain fatty acids. IMPORTANCE: The untapped potential of gluten-degrading bacteria and their application in addressing the recognized limitations of gluten-related disorder management and the ongoing risk of cross-contamination even when people follow a gluten-free diet (GFD) emphasizes the significance of the work. Because gluten, a common protein found in many cereals, must be strictly avoided to stop autoimmune reactions and related health problems, celiac disease and gluten sensitivity present difficult hurdles. However, because of the hidden presence of gluten in many food products and the constant danger of cross-contamination during food preparation and processing, total avoidance is frequently challenging. Our study presents a novel probiotic preparation suitable for people suffering from gluten-related disorders during GFD and for healthy individuals because it enhances gluten digestion and promotes gut microbiota functionality.

Fecal microbiota and concentrations of long-chain fatty acids, sterols, and unconjugated bile acids in cats with chronic enteropathy.

Feline chronic enteropathies (FCE) are common causes of chronic gastrointestinal signs in cats and include different diseases such as food-responsive enteropathy (FRE), inflammatory bowel diseases (IBD), and low-grade intestinal T-cell lymphoma (LGITL). Although changes in intestinal microbiota and fecal metabolites have been reported in dogs and humans with chronic enteropathy, research in cats has been limited. Therefore, this study aimed to evaluate the fecal microbiota and lipid-related fecal metabolites in cats with FCE to a clinically healthy comparison group (CG). A total of 34 cats with FCE (13 FRE, 15 IBD, and 6 LGITL) and 27 cats in the CG were enrolled in this study. The fecal microbiota was evaluated by the qPCR-based feline Dysbiosis Index (DI). The feline DI in cats with CE (median: 1.3, range: -2.4 to 3.8) was significantly higher (p < 0.0001) compared to CG (median: - 2.3, Range: -4.3 to 2.3), with no difference found among the FCE subgroups. The fecal abundances of Faecalibacterium (p < 0.0001), Bacteroides (p < 0.0001), Fusobacterium (p = 0.0398), Bifidobacterium (p = 0.0004), and total bacteria (p = 0.0337) significantly decreased in cats with FCE. Twenty-seven targeted metabolites were measured by gas chromatography-mass spectrometry, including long-chain fatty acids (LCFAs), sterols, and bile acids (BAs). Fecal concentrations of 5 of 12 LCFAs were significantly increased in cats with FCE compared to CG. Fecal concentrations of zoosterol (p = 0.0109), such as cholesterol (p < 0.001) were also significantly increased in cats with FCE, but those of phytosterols were significantly decreased in this group. No differences in fecal BAs were found between the groups. Although no differences were found between the four groups, the fecal metabolomic pattern of cats with FRE was more similar to that of the CG than to those with IBD or LGITL. This could be explained by the mild changes associated with FRE compared to IBD and LGITL. The study showed changes in intestinal microbiota and alteration of fecal metabolites in FCE cats compared to the CG. Changes in fecal lipids metabolites suggest a dysmetabolism of lipids, including LCFAs, sterols, and unconjugated BAs in cats with CE.

A Direct Link Implicating Loss of SLC26A6 to Gut Microbial Dysbiosis, Compromised Barrier Integrity, and Inflammation.

BACKGROUND & AIMS: Putative anion transporter-1 (PAT1, SLC26A6) plays a key role in intestinal oxalate and bicarbonate secretion. PAT1 knockout (PKO) mice exhibit hyperoxaluria and nephrolithiasis. Notably, diseases such as inflammatory bowel disease are also associated with higher risk of hyperoxaluria and nephrolithiasis. However, the potential role of PAT1 deficiency in gut-barrier integrity and susceptibility to colitis is currently elusive. METHODS: Age-matched PKO and wild-type littermates were administered 3.5% dextran sulfate sodium in drinking water for 6 days. Ileum and colon of control and treated mice were harvested. Messenger RNA and protein expression of tight junction proteins were determined by reverse transcription polymerase chain reaction and western blotting. Severity of inflammation was assessed by measuring diarrheal phenotype, cytokine expression, and hematoxylin and eosin staining. Gut microbiome and associated metabolome were analyzed by 16S ribosomal RNA sequencing and mass spectrometry, respectively. RESULTS: PKO mice exhibited significantly higher loss of body weight, gut permeability, colonic inflammation, and diarrhea in response to dextran sulfate sodium treatment. In addition, PKO mice showed microbial dysbiosis and significantly reduced levels of butyrate and butyrate-producing microbes compared with controls. Co-housing wild-type and PKO mice for 4 weeks resulted in PKO-like signatures on the expression of tight junction proteins in the colons of wild-type mice. CONCLUSIONS: Our data demonstrate that loss of PAT1 disrupts gut microbiome and related metabolites, decreases gut-barrier integrity, and increases host susceptibility to intestinal inflammation. These findings, thus, highlight a novel role of the oxalate transporter PAT1 in promoting gut-barrier integrity, and its deficiency appears to contribute to the pathogenesis of inflammatory bowel diseases.

Untargeted Metabolomics Reveals Fruit Secondary Metabolites Alter Bat Nutrient Absorption.

The ecological interaction between fleshy fruits and frugivores is influenced by diverse mixtures of secondary metabolites that naturally occur in the fruit pulp. Although some fruit secondary metabolites have a primary role in defending the pulp against antagonistic frugivores, these metabolites also potentially affect mutualistic interactions. The physiological impact of these secondary metabolites on mutualistic frugivores remains largely unexplored. Using a mutualistic fruit bat (Carollia perspicillata), we showed that ingesting four secondary metabolites commonly found in plant tissues affects bat foraging behavior and induces changes in the fecal metabolome. Our behavioral trials showed that the metabolites tested typically deter bats. Our metabolomic surveys suggest that secondary metabolites alter, either by increasing or decreasing, the absorption of essential macronutrients. These behavioral and physiological effects vary based on the specific identity and concentration of the metabolite tested. Our results also suggest that a portion of the secondary metabolites consumed is excreted by the bat intact or slightly modified. By identifying key shifts in the fecal metabolome of a mutualistic frugivore caused by secondary metabolite consumption, this study improves our understanding of the effects of fruit chemistry on frugivore physiology.

Both viable Bifidobacterium longum subsp. infantis B8762 and heat-killed cells alleviate the intestinal inflammation of DSS-induced IBD rats.

In view of the safety concerns of probiotics, more and more attention is paid to the beneficial effects of dead probiotics cells. Herein, we investigated and compared the alleviation effects of viable Bifidobacterium longum subsp. infantis B8762 (B. infantis B8762) and its heat-killed cells on dextran sodium sulfate (DSS)-induced inflammatory bowel disease (IBD) rats. Four groups of rats (n = 12 per group) were included: normal control, DSS-induced colitis rats without bacterial administration (DSS), DSS-induced colitis rats with viable B. infantis B8762 administration (VB8762), and DSS-induced colitis rats with dead B. infantis B8762 administration (DB8762). Our results showed that both VB8762 and DB8762 administration exerted significant protective effects on DSS-induced IBD rats, as evidenced by a reduction in mortality, disease activity index score, body weight loss, as well as decreased histology score, which were companied by a significant decrease in serum pro-inflammatory factors compared with DSS group, and a stronger effect on modulating the fecal microbiota alpha-diversity and beta-diversity compared with DSS group. Additionally, the fecal metabolome results showed that both VB8762 and DB8762 interventions indeed altered the fecal metabolome profile and related metabolic pathways of DSS-induced IBD rats. Therefore, given the alleviation effects on colitis, the DB8762 can be confirmed to be a postbiotic. Overall, our findings suggested that VB8762 and DB8762 had similar ability to alleviate IBD although with some differences. Due to the minimal safety concern of postbiotics, we propose that the postbiotic DB8762 could be a promising alternative to probiotics to be applied in the prevention and treatment of IBDs.IMPORTANCEInflammatory bowel disease (IBD) has emerged as a global disease because of the worldwide spread of western diets and lifestyles during industrialization. Up to now, many probiotic strains are used as a modulator of gut microbiota or an enhancer of gut barrier to alleviate or cure IBD. However, there are still many issues of using probiotics, which were needed to be concerned about, for instance, safety issues in certain groups like neonates and vulnerable populations, and the functional differences between viable and dead microorganisms. Therefore, it is of interest to investigate the beneficial effects of dead probiotics cells. The present study proved that both viable Bifidobacterium longum subsp. infantis B8762 and heat-killed cells could alleviate dextran sodium sulfate-induced colitis in rats. The findings help to support that some heat-killed probiotics cells can also exert relevant biological functions and can be used as a postbiotic.

Landscapes of gut bacterial and fecal metabolic signatures and their relationship in severe preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific disease leading to maternal and perinatal morbidity. Hypertension and inflammation are the main characteristics of preeclampsia. Many factors can lead to hypertension and inflammation, including gut microbiota which plays an important role in hypertension and inflammation in humans. However, alterations to the gut microbiome and fecal metabolome, and their relationships in severe preeclampsia are not well known. This study aims to identify biomarkers significantly associated with severe preeclampsia and provide a knowledge base for treatments regulating the gut microbiome. METHODS: In this study, fecal samples were collected from individuals with severe preeclampsia and healthy controls for shotgun metagenomic sequencing to evaluate changes in gut microbiota composition. Quantitative polymerase chain reaction analysis was used to validate the reliability of our shotgun metagenomic sequencing results. Additionally, untargeted metabolomics analysis was performed to measure fecal metabolome concentrations. RESULTS: We identified several Lactobacillaceae that were significantly enriched in the gut of healthy controls, including Limosilactobacillus fermentum, the key biomarker distinguishing severe preeclampsia from healthy controls. Limosilactobacillus fermentum was significantly associated with shifts in KEGG Orthology (KO) genes and KEGG pathways of the gut microbiome in severe preeclampsia, such as flagellar assembly. Untargeted fecal metabolome analysis found that severe preeclampsia had higher concentrations of Phenylpropanoate and Agmatine. Increased concentrations of Phenylpropanoate and Agmatine were associated with the abundance of Limosilactobacillus fermentum. Furthermore, all metabolites with higher abundances in healthy controls were enriched in the arginine and proline metabolism pathway. CONCLUSION: Our research indicates that changes in metabolites, possibly due to the gut microbe Limosilactobacillus fermentum, can contribute to the development of severe preeclampsia. This study provides insights into the interaction between gut microbiome and fecal metabolites and offers a basis for improving severe preeclampsia by modulating the gut microbiome.

Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial.

BACKGROUND: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood. OBJECTIVES: Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors. METHODS: A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota. RESULTS: Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors. CONCLUSIONS: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

Altered gut mycobiome in patients with end-stage renal disease and its correlations with serum and fecal metabolomes.

BACKGROUND: The relationship between the gut mycobiome and end-stage renal disease (ESRD) remains largely unexplored. METHODS: In this study, we compared the gut fungal populations of 223 ESRD patients and 69 healthy controls (HCs) based on shotgun metagenomic sequencing data, and analyzed their associations with host serum and fecal metabolites. RESULTS: Our findings revealed that ESRD patients had a higher diversity in the gut mycobiome compared to HCs. Dysbiosis of the gut mycobiome in ESRD patients was characterized by a decrease of Saccharomyces cerevisiae and an increase in various opportunistic pathogens, such as Aspergillus fumigatus, Cladophialophora immunda, Exophiala spinifera, Hortaea werneckii, Trichophyton rubrum, and others. Through multi-omics analysis, we observed a substantial contribution of the gut mycobiome to host serum and fecal metabolomes. The opportunistic pathogens enriched in ESRD patients were frequently and positively correlated with the levels of creatinine, homocysteine, and phenylacetylglycine in the serum. The populations of Saccharomyces, including the HC-enriched Saccharomyces cerevisiae, were frequently and negatively correlated with the levels of various toxic metabolites in the feces. CONCLUSIONS: Our results provided a comprehensive understanding of the associations between the gut mycobiome and the development of ESRD, which had important implications for guiding future therapeutic studies in this field.

Prenatal exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts the maternal gut microbiome and fecal metabolome homeostasis.

Initially considered a "safe" substitute for perfluorooctanoic acid (PFOA), hexafluoropropylene oxide trimer acid (HFPO-TA) has been extensively used in the production of fluoropolymers for several years, leading to its environmental ubiquity and subsequent discovery of its significant bio-accumulative properties and toxicological effects. However, the specific impact of HFPO-TA on females, particularly those who are pregnant, remains unclear. In the present study, pregnant mice were exposed to 0.63 mg/kg/day HFPO-TA from gestational day (GD) 2 to GD 18. We then determined the potential effects of exposure on gut microbiota and fecal metabolites at GD 12 (mid-pregnancy) and GD 18 (late pregnancy). Our results revealed that, in addition to liver damage, HFPO-TA exposure during the specified window altered the structure and function of cecal gut microbiota. Notably, these changes showed the opposite trends at GD 12 and GD 18. Specifically, at GD 12, HFPO-TA exposure primarily resulted in the down-regulation of relative abundances within genera from the Bacteroidetes and Proteobacteria phyla, as well as associated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. With extended exposure time, the down-regulated genera within Proteobacteria became significantly up-regulated, accompanied by corresponding up-regulation of human disease- and inflammation-associated pathways, suggesting that HFPO-TA exposure can induce intestinal inflammation and elevate the risk of infection during late pregnancy. Pearson correlation analysis revealed that disturbances in the gut microbiota were accompanied by abnormal fecal metabolite. Additionally, alterations in hormones related to the steroid hormone biosynthesis pathway at both sacrifice time indicated that HFPO-TA exposure might change the steroid hormone level of pregnant mice, but need further study. In conclusion, this study provides new insights into the mechanisms underlying HFPO-TA-induced adverse effects and increases awareness of potential persistent health risks to pregnant females.

Gut microbiota affects the estrus return of sows by regulating the metabolism of sex steroid hormones.

BACKGROUND: Sex hormones play important roles in the estrus return of post-weaning sows. Previous studies have demonstrated a complex and bi-directional regulation between sex hormones and gut microbiota. However, the extent to which the gut microbiota affects estrus return of post-weaning sows is largely unknown. RESULTS: In this study, we first screened 207 fecal samples from well-phenotyped sows by 16S rRNA gene sequencing and identified significant associations between microbes and estrus return of post-weaning sows. Using metagenomic sequencing data from 85 fecal samples, we identified 37 bacterial species that were significantly associated with estrus return. Normally returning sows were characterized by increased abundances of L. reuteri and P. copri and decreased abundances of B. fragilis, S. suis, and B. pseudolongum. The changes in gut microbial composition significantly altered the functional capacity of steroid hormone biosynthesis in the gut microbiome. The results were confirmed in a validation cohort. Significant changes in sex steroid hormones and related compounds were found between normal and non-return sows via metabolome analysis. An integrated analysis of differential bacterial species, metagenome, and fecal metabolome provided evidence that normal return-associated bacterial species L. reuteri and Prevotella spp. participated in the degradation of pregnenolone, progesterone, and testosterone, thereby promoting estrogen biosynthesis. Furthermore, the microbial metabolites related to sow energy and nutrient supply or metabolic disorders also showed relationships with sow estrus return. CONCLUSIONS: An integrated analysis of differentially abundant bacterial species, metagenome, and fecal metabolome revealed the involvement of L. reuteri and Prevotella spp. in sow estrus return. These findings provide deep insight into the role of gut microbiota in the estrus return of post-weaning sows and the complex cross-talk between gut microbiota and sex hormones, suggesting that the manipulation of the gut microbiota could be an effective strategy to improve sow estrus return after weaning.

Multi-Omics Analysis Reveals Age-Related Microbial and Metabolite Alterations in Non-Human Primates.

Aging is a systemic physiological degenerative process, with alterations in gut microbiota and host metabolism. However, due to the interference of multiple confounding factors, aging-associated molecular characteristics have not been elucidated completely. Therefore, based on 16S ribosomal RNA (rRNA) gene sequencing and non-targeted metabolomic detection, our study systematically analyzed the composition and function of the gut microbiome, serum, and fecal metabolome of 36 male rhesus monkeys spanning from 3 to 26 years old, which completely covers juvenile, adult, and old stages. We observed significant correlations between 41 gut genera and age. Moreover, 86 fecal and 49 serum metabolites exhibited significant age-related correlations, primarily categorized into lipids and lipid-like molecules, organic oxygen compounds, organic acids and derivatives, and organoheterocyclic compounds. Further results suggested that aging is associated with significant downregulation of various amino acids constituting proteins, elevation of lipids, particularly saturated fatty acids, and steroids. Additionally, age-dependent changes were observed in multiple immune-regulatory molecules, antioxidant stress metabolites, and neurotransmitters. Notably, multiple age-dependent genera showed strong correlations in these changes. Together, our results provided new evidence for changing characteristics of gut microbes and host metabolism during aging. However, more research is needed in the future to verify our findings.

Fecal Concentrations of Long-Chain Fatty Acids, Sterols, and Unconjugated Bile Acids in Cats with Chronic Enteropathy.

Chronic enteropathy (CE) in cats encompasses food-responsive enteropathy, chronic inflammatory enteropathy (or inflammatory bowel disease), and low-grade intestinal T-cell lymphoma. While alterations in the gut metabolome have been extensively studied in humans and dogs with gastrointestinal disorders, little is known about the specific metabolic profile of cats with CE. As lipids take part in energy storage, inflammation, and cellular structure, investigating the lipid profile in cats with CE is crucial. This study aimed to measure fecal concentrations of various fatty acids, sterols, and bile acids. Fecal samples from 56 cats with CE and 77 healthy control cats were analyzed using gas chromatography-mass spectrometry, targeting 12 fatty acids, 10 sterols, and 5 unconjugated bile acids. Fecal concentrations of nine targeted fatty acids and animal-derived sterols were significantly increased in cats with CE. However, fecal concentrations of plant-derived sterols were significantly decreased in cats with CE. Additionally, an increased percentage of primary bile acids was observed in a subset of cats with CE. These findings suggest the presence of lipid maldigestion, malabsorption, and inflammation in the gastrointestinal tract of cats with CE. Understanding the lipid alterations in cats with CE can provide insights into the disease mechanisms and potential future therapeutic strategies.

Microbial modifications with Lycium barbarum L. oligosaccharides decrease hepatic fibrosis and mitochondrial abnormalities in mice.

BACKGROUND: Lycium barbarum L. is a typical Chinese herbal and edible plant and are now consumed globally. Low molecular weight L. barbarum L. oligosaccharides (LBO) exhibit better antioxidant activity and gastrointestinal digestibility in vitro than high molecular weight polysaccharides. However, the LBO on the treatment of liver disease is not studied. PURPOSE: Modification of the gut microbial ecosystem by LBO is a promising treatment for liver fibrosis. STUDY DESIGN AND METHODS: Herein, LBO were prepared and characterized. CCl4-treated mice were orally gavaged with LBO and the effects on hepatic fibrosis and mitochondrial abnormalities were evaluated according to relevant indicators (gut microbiota, faecal metabolites, and physiological and biochemical indices). RESULTS: The results revealed that LBO, a potential prebiotic source, is a pyranose cyclic oligosaccharide possessing α-glycosidic and ß-glycosidic bonds. Moreover, LBO supplementation restored the configuration of the bacterial community, enhanced the proliferation of beneficial species in the gastrointestinal tract (e.g., Bacillus, Tyzzerella, Fournierella and Coriobacteriaceae UCG-002), improved microbial metabolic alterations (i.e., carbohydrate metabolism, vitamin metabolism and entero-hepatic circulation), and increased antioxidants, including doxepin, in mice. Finally, LBO administration reduced serum inflammatory cytokine and hepatic hydroxyproline levels, improved intestinal and hepatic mitochondrial functions, and ameliorated mouse liver fibrosis. CONCLUSION: These findings indicate that LBO can be utilized as a prebiotic and has a remarkable ability to mitigate liver fibrosis.

Effects of Electroacupuncture on Gut Microbiota and Fecal Metabolites in Rats with Poststroke Depression.

Background: Poststroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. Electroacupuncture (EA) has been found to be an effective therapy for treating PSD. However, the underlying mechanisms of EA's efficacy remain unclear. This research aimed to investigate the effects of EA on alterations in gut microbiota and fecal metabolome in PSD rats. Methods: Analyses of gut microbiome and fecal metabolome were performed to identify gut microbes and their functional metabolites in a sham group, PSD group, and EA group. We conducted enrichment analysis to identify the differential metabolic pathways in three groups. Correlations between altered gut microbes and differential metabolites after EA treatment were studied. Results: PSD showed decreased species-richness/diversity indices of microbial composition, characterized by an increase in Muribaculaceae, Peptostreptococcaceae, Oscillospiraceae, Ruminococcaceae, and Clostridiaceae and a decrease in Lactobacillaceae, Lachnospiraceae, and Bacteroidaceae. Of these, the abundance of Muribaculaceae, Lactobacillaceae, Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were reversed by EA. Furthermore, PSD was associated with 34 differential fecal metabolites, mainly belonging to steroid hormone biosynthesis, that could be regulated by EA. Conclusion: Regulation of gut microbiome and lipid metabolism could be one of the potential mechanisms for EA treatment for alleviating the depressive behaviors of PSD.

Effects of Ganoderma lucidum polysaccharide peptide ameliorating cyclophosphamide-induced immune dysfunctions based on metabolomics analysis.

Ganoderma lucidum polysaccharide peptide (GLPP) is one of the most abundant constituents of Ganoderma lucidum (G. lucidum), with a wide range of functional activities. The present study investigated the immunomodulatory effects of GLPP in cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that 100 mg/kg/day of GLPP administration significantly alleviated CTX-induced immune damage by improving immune organ indexes, earlap swelling rate, the index of carbon phagocytosis and clearance value, secretion of cytokines (TNF-α, IFN-γ, and IL-2), and immunoglobulin A(IgA) in the mice. Furthermore, ultra-performance liquid chromatography with mass/mass spectrometry (UPLC-MS/MS) was conducted to identify the metabolites, followed by biomarker and pathway analysis. The results showed that GLPP treatment alleviated CTX-induced alterations in the fecal metabolome profile, including arachidonic acid (AA), leukotriene D4 (LTD4), indole-3-ethanol, and formyltetrahydrofolate (CF), by reversing citric acid, malic acid, cortisol, and oleic acid. These results support the concept that GLPP exhibits immunomodulatory activity via the folate cycle, methionine cycle, TCA cycle, fatty acid biosynthesis and metabolism, glycerophospholipid metabolism, AA metabolism, and cAMP pathways. In conclusion, the results could be helpful to understand the use of GLPP to clarify the immunomodulatory mechanism and be used as immunostimulants to prevent CTX-induced side effects in the immune system.

Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study.

Chronic constipation (CC) is a common gastrointestinal condition associated with intestinal inflammation, and the condition considerably impairs patients' quality of life. We conducted a large-scale 42-day randomized, double-blind, placebo-controlled trial to investigate the effect of probiotics in alleviating CC. 163 patients diagnosed with CC (following Rome IV criteria) were randomly divided into probiotic (n = 78; received Lactiplantibacillus plantarum P9 [P9]; 1 ×1011 CFU/day) and placebo (n = 85; received placebo material) groups. Ingesting P9 significantly improved the weekly mean frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), while significantly reducing the level of worries and concerns (WO; P < 0.05). Comparing with the placebo group, P9 group was significantly enriched in potentially beneficial bacteria (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), while depriving of several bacterial and phage taxa (Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae; P < 0.05). Interesting significant correlations were also observed between some clinical parameters and subjects' gut microbiome, including: negative correlation between Oscillospiraceae sp. and SBMs; positive correlation between WO and Oscillospiraceae sp., Lachnospiraceae sp. Additionally, P9 group had significantly (P < 0.05) more predicted gut microbial bioactive potential involved in the metabolism of amino acids (L-asparagine, L-pipecolinic acid), short-/medium-chain fatty acids (valeric acid and caprylic acid). Furthermore, several metabolites (p-cresol, methylamine, trimethylamine) related to the intestinal barrier and transit decreased significantly after P9 administration (P < 0.05). In short, the constipation relief effect of P9 intervention was accompanied by desirable changes in the fecal metagenome and metabolome. Our findings support the notion of applying probiotics in managing CC.