Search Results (2,081)

Background: Obesity is a highly prevalent chronic disease characterized by excessive weight gain and fat accumulation. There is growing evidence that Lactiplantibacillus plantarum strains with bile salt hydrolase (BSH) activity are effective in preventing and alleviating obesity. Methods: Initially, we screened bacterial strains with high hydrolytic activity against glycochenodeoxycholic acid (GDCA), and constructed an isogenic bsh1 knockout mutant. Subsequently, male C57BL/6J mice fed a high-fat diet (HFD) were randomly assigned to receive daily gavage of either the wild-type Lp20 (Lp20-WT) or the bsh1-deficient mutant (Lp20-Δbsh1) for 8 weeks. Serum cholesterol levels and histopathological changes in liver sections were monitored. Hepatic gene expression was quantified by RT-qPCR, and fecal bacterial communities were analyzed via 16S rRNA gene sequencing. These comprehensive assessments aimed to evaluate metabolic improvements and uncover the potential mechanisms behind the observed effects. Results:L. plantarum Lp20 hydrolyzed 91.62% of GDCA, exhibiting the highest bile-salt hydrolase (BSH) activity among tested isolates. Whole-genome sequencing and in-silico analyses mapped this activity to bsh1; gene deletion of bsh1 confirmed the role of bsh1 in GDCA hydrolysis. Daily gavage of the wild-type strain (Lp20-WT) to diet-induced obese mice markedly attenuated weight gain, reduced inguinal white adipose tissue and mesenteric fat mass, and lowered serum TC and LDL-C by 20.8% and 33.3%, respectively, while decreasing ALT and AST levels and reversing hepatic steatosis. In contrast, the bsh1-null mutant (Lp20-Δbsh1) failed to elicit any measurable metabolic benefit. Mechanistically, Lp20-WT upregulated rate-limiting bile-acid synthetic enzymes CYP7A1 and CYP27A1, thereby accelerating the catabolism of cholesterol into bile acids. Concurrently, it activated hepatic TGR5 and FXR signaling axes to modulate hepatic metabolism. Moreover, Lp20-WT restructured the gut microbiota by notably enhancing the abundance of beneficial bacteria such as norank_f__Muribaculaceae, Akkermansia, and Alistipes, while reducing the abundance of potentially harmful taxa, including norank_f__Desulfovibrionaceae, Dubosiella, and Mucispirillum. Conclusions: This study provides direct evidence of BSH’s anti-obesity effects through gene deletion. Specifically, BSH lowers cholesterol by modulating hepatic bile-acid metabolism-related gene expression and altering the gut microbiota composition. However, the study is limited by a small sample size (n = 6), the use of male mice only, and its preclinical stage, indicating a need for further validation across diverse strains and human populations. Full article

Background: High-throughput metabolomics studies have promoted the discovery of candidate biomarkers linked to atherosclerosis (AS). This narrative systematic review summarises metabolomics studies conducted in (1) individuals with subclinical AS (assessed by imaging techniques such as carotid intimal media thickness, IMT, and coronary artery calcium, CAC), (2) patients with established atherosclerotic plaques, and (3) individuals with AS risk factors. Methods: The systematic search was conducted in the PubMed database according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were as follows: (i) publication date between 2009 and 2024; (ii) identification of potential biomarkers for AS in subjects with a diagnosis of AS or with one or more traits characteristic of the disease (i.e., CAC or IMT); (iii) identification of potential AS biomarkers in subjects with atherogenic clinical conditions (i.e., Down’s syndrome, DS, polycystic ovarian syndrome, PCOS, and systemic lupus erythematosus, SLE); (iv) metabolomic studies; and (iv) studies in human samples. Exclusion criteria comprised the following: (i) studies on lipid metabolic diseases unrelated to AS, (ii) “omics” results not derived from metabolomics, (iii) reviews and studies in animal models or cell cultures, and (iv) systematic reviews and meta-analyses. Of 90 eligible studies screened, 24 met the inclusion criteria. Results: Across subclinical and overt AS, consistent disturbances were observed in amino acid, lipid, and carbohydrate metabolism. Altered profiles included branched-chain amino acids (BCAAs), aromatic amino acids (AACs) and derivatives (e.g., kynurenine–tryptophan pathway), bile acids (BAs), androgenic steroids, short-chain fatty acids (FAs)/ketone intermediates (e.g., acetate, 3-hydroxybutyrate, 3-HB), and Krebs cycle intermediates (e.g., citrate). Several metabolites (e.g., glutamine, lactate, 3-HB, phosphatidylcholines, PCs/lysophosphatidylcholines, lyso-PCs) showed reproducible associations with vascular phenotypes (IMT/CAC) and/or clinical AS. Conclusions: The identification of low-weight metabolites altered in both subclinical and overt AS suggests their potential as candidate biomarkers for early AS diagnosis. Given the steady increase in deaths from cardiovascular disease, a manifestation of advanced AS, this finding could have significant clinical relevance. Full article

The interaction between the gut microbiota and the host immune system is pivotal in maintaining health or driving disease pathogenesis. The gut microbiota directly or indirectly modulates immune cells activation and inflammatory cytokines secretion through microbial metabolites, including short-chain fatty acids (SCFAs), tryptophan metabolites, bile acids, and polyamines. Conversely, the immune system regulates microbial community composition by maintaining the integrity of the epithelial barrier. In addition, antibiotics and probiotics can further regulate the inflammatory response by altering gut microbiota structure and microbial metabolites levels. This review systematically examines the bidirectional regulatory mechanisms among the gut microbiota, microbial metabolites, and inflammatory cytokines, and explores the impact of antibiotics and probiotics on this interaction network. These insights provide new targets for immune-related diseases. Full article

Background: There are differences in lipid metabolism by sex that are relevant for health, but metabolic pathways are not fully understood. We investigated sex differences in cross-sectional associations between metabolic pathways identified using untargeted metabolomics and clinical lipid measures (total cholesterol [TC], triglycerides [TG], and low- and high-density lipoprotein cholesterol [LDL-c; HDL-c]) from blood plasma in the Coronary Artery Risk Development in Young Adults (CARDIA) study (Year 20; 2005–2006). Our objective was to determine whether associations between metabolic pathways and lipid measures differ by sex and to identify pathways that may underlie sex-specific mechanisms of lipid metabolism. Methods: Using data from 2169 participants, (44% women, mean age = 45, 58% White, 42% Black), we used: (1) Orthogonal partial least squares-regression (OPLS-R) to compare variation in TC, TG, LDL-c, and HDL-c explained by metabolites in men vs. women, (2) linear regression to assess sex-modification of associations between 7255 metabolite peaks and lipid measures using false discovery rate (FDR)-corrected p < 0.1, and (3) pathway enrichment analyses to identify metabolic pathways that differed by sex using Fisher’s exact test (FET) p < 0.05. Results: We found that: (1) untargeted metabolomic data reflected variation in lipid measures better for men compared to women, (2) associations between metabolite peaks and lipid measures differed by sex, and (3) 8 unique pathways differed by sex, particularly primary bile acid biosynthesis, linoleic acid metabolism, and arginine biosynthesis. Conclusions: Our findings suggest distinct lipid-associated metabolic activity by sex that points to potential mechanistic pathways. Full article

Reducing dietary crude protein (CP) while sustaining growth performance and minimizing nitrogen emissions is a critical challenge in swine production. Beyond growth efficiency, the influence of low-protein diets (LPDs) on meat quality traits, gut microbiota, and systemic metabolism in finishing pigs remains insufficiently understood. In this study, 180 healthy crossbred finishing pigs (Duroc × Liangguang Small Spotted; initial body weight 85.49 ± 4.90 kg) were assigned to three dietary regimens for 35 days (six replicate pens per treatment, ten pigs per pen, male/female = 1:1): Control (CON, 15.5% CP), Low-Protein 1 (LP1, 14.5% CP), and Low-Protein 2 (LP2, 13.5% CP). Growth performance and nutrient digestibility were not impaired by protein reduction. Notably, LP1 pigs exhibited thicker backfat (p < 0.05), while LP2 pigs showed decreased concentrations of specific fatty acids (C12:0–C22:1n9) and essential amino acids (aspartic acid, glutamic acid, lysine) compared with LP1 (p < 0.05), indicating that dietary protein levels affected muscle composition. Cecal microbiota analysis revealed distinct shifts, with Prevotella spp., Faecalibacterium spp., and Plesiomonas spp. enriched in CON, whereas LP1 promoted Eubacteriaceae spp., Christensenellaceae spp., and Clostridia spp. (p < 0.05). Serum metabolomics further distinguished groups: LP1 reduced bile secretion and cholesterol metabolism pathways (p < 0.05) and LP2 further suppressed cholesterol metabolism and primary bile acid biosynthesis (p < 0.05), with a trend toward reduced phenylalanine metabolism (p = 0.07). Collectively, these findings demonstrate that moderate dietary protein reduction, when balanced with essential amino acids, maintains growth, reduces nitrogen output, and beneficially alters muscle composition, gut microbiota, and host metabolic pathways, offering nutritional strategies to enhance pork quality and promote sustainable pig production. Full article

Chronic cold stress is a severe test that animals in cold regions have to face during winter. However, the lack of precise dietary adjustments for animals in cold regions represents a significant gap in addressing their nutritional needs. Full-fat rice bran is one of the feed materials rich in protein, lipids, dietary fiber, and antioxidant-active substances. Glucose is the most common quick energy supply. We determined dietary full-fat rice bran and glucose can improve the growth and health of cold-exposed pigs. A total of 18 Yorkshire pigs were randomized to one of three treatment groups (basal diet, full-fat rice bran diet (20%), and glucose diet (10%)) for 22 d to evaluate the effects of full-fat rice bran and glucose on growth performance, antioxidants, microbiomes, and bile acid circulation in cold-exposed pigs. The results showed that dietary full-fat rice bran decreased the average daily feed intake (p < 0.05), increased superoxide dismutase (SOD) activity in plasma (p < 0.05), and decreased Rikenellaceae_RC9_gut_group and Campylobacter in the colon microbiota of cold-exposed pigs (p < 0.05). Dietary glucose improved the growth performance of cold-exposed pigs and decreased the abundance of Prevotellaceae_NK3B31_group (p < 0.05) in the colon microbiota of cold-exposed pigs. Dietary full-fat rice bran and glucose both downregulated the abundance of Alloprevotella, Bradymonadales, and Erysipelotrichaceae in colon microbiota (p < 0.05), promoted the production of SCFAs, and activated the FXR-CYP7A1 signaling pathway. Dietary full-fat rice bran or glucose promoted fecal excretion of bile acids. This study demonstrated that dietary supplementation with full-fat rice bran or glucose can improve the colonic microbiota structure and SCFA levels in cold-exposed pigs. When comparing the two dietary strategies, the glucose-supplemented diet is more beneficial to the growth performance of cold-exposed pigs, while the full-fat-rice-bran-supplemented diet is more conducive to enhancing the function of their antioxidant system. Additionally, dietary supplementation with full-fat rice bran or glucose can also regulate the bile acid circulation in pigs, thereby enhancing their cold adaptation ability. Full article

A free-ranging 10-month-old male American black bear (Ursus americanus) was presented to a rehabilitation facility in eastern Tennessee for being orphaned and emaciated, and was diagnosed with bile duct stenosis, leading to euthanasia. On initial intake, liver values including gamma-glutamyl transferase, alanine aminotransferase, and serum bile acids were elevated. The cub was treated for intestinal parasites and discharged to a rehabilitation facility for monitoring. Three weeks later, all liver values markedly increased despite improvements in body condition, appetite, and overall energy level. Abdominal ultrasound and dual phase computed tomography confirmed stenosis of the biliary outflow tract with gallbladder dilation and bile ducts in two locations. Surgical treatment and release were not performed due to the lack of clinical follow-up, likelihood of a genetic anomaly, and risk of it being passed to offspring. Necropsy findings further confirmed the bile duct stenosis with chronic regionally extensive fibrosis. The cause of this lesion is hypothesized to be congenital; however, inflammation secondary to a previous infection was not able to be ruled out. This case report documents the presentation and multidisciplinary approach to diagnosing a juvenile bear with bile duct stenosis, not previously reported in the literature. Full article

Background: Some lactobacilli strains have been documented to cause bacteremia and sepsis in immunocompromised or critically ill hospitalized patients, challenging the universally presumed safety of lactobacilli. Therefore, strain-specific risk assessments are required for the use of Lactobacillus as a probiotic. Lactobacillus xujianguonis, a novel Lactobacillus species isolated from Marmota himalayana, has probiotic potential but lacks safety data. Objective: To evaluate the preclinical safety of L. xujianguonis for food-grade use. Methods: Systematic safety assessment includes in vitro studies and oral toxicity studies. In vitro studies encompassed gastrointestinal tolerance, auto-aggregation and pathogen inhibition, antibiotic susceptibility, and hemolysis/gelatinase activity assays. Oral toxicity studies contained acute single-dose and repeated-dose 28-day oral toxicity studies in mice based on the OECD toxicity study guidelines. Results: L. xujianguonis strains HT111-2 and 06-2 demonstrated certain probiotic traits, including high acid/bile tolerance, strong auto-aggregation, and antimicrobial activity against common human gastrointestinal pathogens. In vitro safety assessments showed susceptibility to nine antibiotics and absence of hemolytic/gelatinase activity. Acute oral exposure (1 × 10¹¹ CFU/kg) induced no mortality, clinical abnormalities, or organ toxicity. Subchronic 28-day administration (multiple doses) showed absence of adverse clinical signs with body weight stability and no hematological, biochemical, or histopathological deviations in C57BL/6 mice. Inflammatory and immunological markers remained unaffected. Histological staining results and transcriptional level validation revealed no evidence of intestinal tissue damage. Conclusions: This study provides preliminary evidence of the safety of L. xujianguonis, supporting its advancement to functional research. Full article

Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive bile duct inflammation and fibrosis. Its strong association with inflammatory bowel disease (IBD) highlights the possible role of the gut–liver axis in disease pathogenesis. Here, we review the mechanisms that may contribute to the disruption of the gut–liver axis, leading to liver injury and the development of PSC. In particular, disruption of the intestinal barrier allows microbial products to enter the portal circulation, stimulating hepatic immune cells and triggering biliary inflammation. Concurrently, gut-primed lymphocytes expressing mucosal homing receptors migrate aberrantly to the liver, where they may contribute to biliary epithelial cell injury. Dysbiosis, characterized by reduced microbial diversity and the expansion of bile-tolerant and pro-inflammatory taxa, amplifies this immune activation and disturbs gut–liver homeostasis. Moreover, bile acids act as signaling molecules, regulating metabolism and immune responses through receptors such as FXR and TGR5. Dysregulation of these pathways may promote cholestasis, inflammation, and fibrosis. By understanding these interactions, we may identify novel therapeutic targets for PSC. Full article

Xanthohumol (XN), a polyphenol from hops (Humulus lupulus), exhibits antioxidant, anti-inflammatory, antihyperlipidemic, and chemo-preventive activity. Preclinical evidence suggests gut microbiota are critical to mediating some of these bioactivities. Nevertheless, its precise impact on human gut microbiota, particularly at supplemental doses, remains poorly characterized. We evaluated 200 mg/day XN for 3 weeks on human gut microbiota in a eubiotic and dysbiotic model using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®). Functional assessments of microbiota included quantification of XN metabolites, short-chain fatty acids (SCFAs), and untargeted metabolomics of the digestive metabolome. Bacterial composition was assessed by 16S rRNA gene sequencing. XN reduced alpha-diversity and short-chain fatty acid production in both models, as well as altered taxa abundance variably between models. XN disrupted bile acid metabolism through inhibition of microbial bile salt hydrolase (BSH). The modulation of bile acid metabolism has important implications for host-level bioactivity of XN. Full article

Clostridioides difficile infection (CDI) is a major complication in inflammatory bowel disease (IBD), due to coexistence of altered microbiota, chronic inflammation, and immune dysregulation. This narrative review summarizes recent evidence on the epidemiology, pathogenesis, risk factors, diagnosis, and management of CDI in IBD. Overall, IBD patients have a four- to five-fold higher risk of CDI than the general population and face more severe courses, higher rates of hospitalization, colectomy, recurrence, and mortality. Pathogenesis involves profound dysbiosis with loss of butyrate-producing Firmicutes and Bacteroidetes, bile acid imbalance that promotes spore germination, and enhanced toxin effects on an already inflamed mucosa. Major risk factors include active colonic disease, broad-spectrum antibiotic exposure, prolonged hospitalization, and corticosteroid or combined immunosuppressive therapy. Diagnosis requires careful integration of stool assays with clinical evaluation, supported by endoscopy or imaging when needed, to distinguish infection from IBD flares. Recommended first-line treatments are fidaxomicin or oral vancomycin, reserving fecal microbiota transplantation for recurrent or high-risk cases. Optimal IBD control is essential to reduce both primary and recurrent infection. CDI and IBD share a mutual pathogenic interplay in which microbial, immune, and therapeutic factors from each condition drive and magnify the other. Early recognition, guideline-based antibiotic therapy, judicious use of immunosuppression, and microbiota-based preventive strategies are crucial to improve patient outcomes and limit recurrence, thus reducing healthcare costs. Full article

Commercial feeds formulated for Larimichthys crocea are commonly used in intensive farming of Larimichthys polyactis; however, their nutritional composition is suboptimal for the latter. The study evaluated the effects of dietary chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) supplementation on mitigating nutritional mismatch-induced growth retardation and hepatopancreatic–intestinal metabolic disorders in L. polyactis. Fish were fed seven feeds: a commercial feed (control) and feeds supplemented with 300, 600, and 1200 mg/kg of CDCA or UDCA. Results showed that both bile acids (BAs) supplementation improved growth, altered thyroid hormone metabolism, with significant changes in hepatopancreatic–intestinal types of deiodination. Both BAs increased hepatopancreatic energy metabolism and cholic acid synthesis, while inducing hepatopancreatic oxidative damage. Notably, 300 mg/kg CDCA and 600 mg/kg UDCA significantly reduced hepatopancreatic vacuolation and lipid accumulation, which was associated with enhanced protease and lipase activities (p < 0.05). Dietary both BAs supplementation enhanced intestinal antioxidant capacity, but contributed to the inflammation, with 300 mg/kg UDCA improving intestinal mucosal morphology (p < 0.05). These findings suggest that supplementation with dietary 300 mg/kg CDCA, 300 and 600 mg/kg UDCA could alleviate growth restriction and liver–intestinal structural damage caused by nutritional mismatch, reduce hepatic fat accumulation, and enhance intestinal antioxidant capacity of L. polyactis. Full article

Mastitis represents one of the most economically devastating diseases in dairy production, causing billions of dollars in annual losses through reduced milk quality and quantity. Recent advances in microbiome research have unveiled a critical gut–mammary axis that fundamentally influences mastitis susceptibility and pathogenesis in dairy cattle. Through comprehensive analysis of microbial communities across multiple anatomical sites, we demonstrate that mastitis development involves systematic disruption of both mammary and gastrointestinal microbiomes, characterized by reduced beneficial bacterial populations and increased pathogenic species. Healthy animals maintain balanced microbial ecosystems dominated by protective taxa including Firmicutes, Bacteroidetes, and beneficial Lactobacillus species, while mastitis-affected animals exhibit dysbiotic shifts toward Proteobacteria dominance, elevated Streptococcus and Staphylococcus populations, and compromised microbial diversity. Mechanistic investigations reveal that gut microbiota disruption compromises systemic immune competence, alters metabolite production including short-chain fatty acids and bile acids, and influences inflammatory mediators that circulate to mammary tissue. Therapeutic interventions targeting this axis, including probiotics, prebiotics, and plant-derived compounds, demonstrate significant efficacy in restoring microbiome homeostasis and reducing mastitis severity. These findings establish the gut–mammary axis as a fundamental regulatory mechanism in mastitis pathogenesis, opening new avenues for microbiome-based prevention and treatment strategies that could significantly enhance dairy health management while addressing antimicrobial resistance concerns. Full article

Bile acids, the primary components of bile, are cholesterol-derived molecules synthesized in the liver and secreted to the small intestine. Besides their primary digestive roles, bile acids have antimicrobial properties and serve as an environmental cue for intestinal pathogens, modulating the expression of virulence factors, e.g., toxins and effector proteins. Whereas timely recognition and neutralization of pathogenic toxin effectors by the host is critical, our understanding of the effects of bile on their structure and function is limited. In this work, we found that bile effectively protected cultured IEC-18 enterocytes from the mixture of Aeromonas hydrophila secreted toxins, containing hemolysin, aerolysin, and RtxA (MARTX). To explore whether these effects have broad specificity, we employed biochemical and biophysical techniques to test the in vitro effects of bile and bile acids on several effector domains of MARTX and VgrG toxins from Vibrio cholerae and Aeromonas hydrophila, and catalytic domains of TcdA and TcdB toxins from Clostridioides difficile. Bile compromised the structural integrity of the tested effectors to various degrees in a protein charge-dependent manner. Bile and bile acids promoted exposure of hydrophobic residues and the unfolding of most, but not all, of the tested effectors, facilitating their precipitation and cleavage by chymotrypsin. Bile also inhibited specific activities of the tested effector enzymes, partially due to imposed oxidation of their catalytic residues. To summarize, this work validated bile as a non-proteinaceous factor of innate immunity, capable of compromising the structural integrity and function of the effector domains of various bacterial toxins. Full article

Phytotherapy is a growing field of modern medicine, offering natural alternatives with multidirectional pharmacological effects. Among plant-derived bioactive compounds, isoquinoline alkaloids exhibit antioxidant, anti-inflammatory, and antimicrobial properties. Our in vitro model of campylobacteriosis confirmed that berberine reduces pathological changes in colonocytes not only through its direct antibacterial (minimum inhibitory concentration for pure berberine against Campylobacter jejuni was 64 μg/mL) and anti-biofilm (fourfold reduction in C. jejuni biomass) effects, but also through its protective effect on the morphostructure and secretory profile of host cells exposed to bacterial components. Furthermore, berberine stabilized intercellular junction proteins, modulated bile acid and arachidonic acid metabolism, and supported host-protective signaling pathways. These findings indicate that berberine acts through a dual mechanism—directly reducing bacterial virulence while enhancing intestinal barrier integrity and metabolic homeostasis. In summary, berberine appears to be a multifunctional phytochemical in the development of new strategies for the prevention and treatment of C. jejuni-induced gastrointestinal infections and epithelial barrier dysfunctions. The protective effect we have demonstrated may contribute to alleviating the phenomenon of “leaky gut,” commonly associated with campylobacteriosis. Full article