Search Results (35)

Hypertension is a common cardiovascular disorder, and current pharmacological treatments are often associated with significant side effects, highlighting the need for safer alternatives. Probiotics and their postbiotics have emerged as promising candidates due to their favorable safety profiles. This study evaluated the potential of Lactobacillus plantarum IOB602 and its 602P postbiotic to attenuate hypertension-induced damage. We first assessed their ACE inhibitory activity in vitro. Subsequently, we investigated their protective effects against organ damage and the underlying mechanisms in L-NAME-induced hypertensive rats using biochemical assays, real-time qPCR, histopathological analysis, and 16S rRNA sequencing. In vitro results showed that IOB602 exhibited strong tolerance to simulated gastric acid and bile salts, indicating good gastrointestinal survivability. Both the culture supernatant and the postbiotic displayed significant ACE inhibitory activity, with the postbiotic achieving an inhibition rate of 82.21%. In vivo, treatment with IOB602 or 602P significantly reduced plasma angiotensin II levels, upregulated the PI3K-Akt-eNOS pathway, restored nitric oxide bioavailability, and attenuated oxidative stress and inflammatory responses in hypertensive rats. Histological analysis revealed that both interventions alleviated pathological damage in the thoracic aorta, heart, and kidneys. Furthermore, IOB602 and its postbiotic reshaped the gut microbiota composition by decreasing harmful genera such as Ruminococcus and enriching beneficial taxa including Akkermansia and Christensenellaceae. In conclusion, L. plantarum IOB602 and its 602P postbiotic show potential for development as functional foods or pharmaceutical adjuvants for the treatment of hypertension-induced organ damage.: Full article

Older age is a well-established risk factor for many chronic diseases, yet the biological mechanisms underlying this increased risk are not fully understood. Both gut microbiome composition and the plasma metabolome change with age and may help explain how aging influences disease susceptibility. In this study, we examined the associations between age-related gut microbiota and metabolomic biomarkers in participants of the Baltimore Longitudinal Study of Aging (BLSA), covering a broad age range (27–98 years; 55% female). At the phylum level, we identified four age-associated phyla: Firmicutes, which was negatively associated with age, and Proteobacteria, Euryarchaeota, and Verrucomicrobia, which were positively associated with age. At the genus level, six genera—Akkermansia, Escherichia, Klebsiella, Methanobrevibacter, Oscillibacter, and Ruthenibacterium—were positively associated with age, whereas Faecalibacterium and Longibaculum were negatively associated with age. Many of these microbial taxa were found to influence one or more aging-related metabolites, mediating their effects across various metabolite classes, including bile acids, amino acids, triglycerides, cholesteryl esters, and phosphatidylcholines. Notably, three metabolites, Asparagine, Sphingomyelin C26:0, and Dihydroceramide (d18:0/24:1), were associated with a decreased risk of mortality, whereas six metabolites—Glycoursodeoxycholic acid, Triacylglyceride (16:1_34:3), Triacylglyceride (18:0_34:3), Phosphatidylcholine aa C32:1, Phosphatidylcholine aa C32:2, and Cholesteryl ester 16:1—were linked to an increased risk of mortality. This study highlights connections between age-associated gut microbial taxa at both the phylum and genus levels as potential mediators of circulating metabolites that are linked to mortality risk. Full article

Background: COVID-19, caused by SARS-CoV-2, exhibits highly variable severity, from mild symptoms to respiratory failure and multiorgan dysfunction. Traditional risk factors incompletely explain this heterogeneity, highlighting the potential role of gut microbiota and host metabolomics in modulating immune responses. Methods: Thus, this study investigates how gut microbiota variations are associated with plasma metabolite profiles in COVID-19, exploring relationships between microbial and metabolic signatures and disease severity and potential therapeutic targets. In a prospective cohort of 55 patients, stool and plasma samples were analyzed using 16S rRNA sequencing and untargeted LC-HRMS metabolomics. Results: Severe COVID-19 was associated with reduced microbial diversity and enrichment of pro-inflammatory taxa, including Prevotella, Alistipes, Dialister, and Lachnoclostridium, whereas mild cases showed higher abundance of protective commensals such as Bacteroides, Faecalibacterium, and Blautia. Metabolomic profiling revealed alterations in bile acids, unsaturated fatty acids, tryptophan, and inositol phosphate pathways. Notably, linoleate levels were elevated in severe cases, showing correlations with pro-inflammatory microbes, while acylcarnitines and inositol derivatives were enriched in mild disease. Predictive functional analysis suggested that severe-associated microbes showed enhanced amino acid catabolism, oxidative glucose metabolism, and xenobiotic degradation, which may be linked to host inflammation. Conclusions: These findings highlight associations between gut microbiota composition, microbial metabolism, and circulating metabolites in COVID-19 severity. Identified microbial and metabolomic signatures may represent potential candidates to be considered biomarkers and therapeutic targets to modulate disease progression. Full article

The replacement of fishmeal with plant-based proteins in aquafeeds is key for sustainable aquaculture but may compromise filet pigmentation in rainbow trout (Oncorhynchus mykiss), a quality trait dependent on astaxanthin (Ax) deposition and metabolism. This study aimed to assess the effects of graded fishmeal replacement with a plant protein blend on Ax retention, pigmentation, lipid metabolism, and gut microbiota composition. Rainbow trout were fed three isoenergetic diets containing 60%, 36%, or 12% fishmeal, each supplemented with equal amounts of natural Ax from Haematococcus pluvialis, for 12 weeks. Ax retention, pigmentation, plasma metabolites, lipid digestibility, and distal intestinal microbiota were evaluated. The high plant protein diet (12% fishmeal) significantly reduced Ax concentrations in filet and plasma and decreased dorsal and belly pigmentation scores (p < 0.05). It also lowered plasma cholesterol and bile acid levels by 18–30%, reduced di-esterified Ax digestibility by 15%, and lipid absorption efficiency by 12%. The gut microbiota shifted significantly, with a marked reduction in Bacillaceae, positively correlated with Ax retention and pigmentation. Fish fed High Plant Meal diets exhibited impaired performance parameters, along with reduced lipid accumulation in the liver. High plant meal compromises Ax bioavailability by altering cholesterol–bile acid metabolism and gut microbiota, impairing Ax absorption. However, moderate inclusion of plant meal preserved pigmentation, underscoring the need for dietary cholesterol management and microbiota modulation in plant-based aquafeeds. Full article

Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive malignancies, with dismal survival rates. Cannabinoids have shown anticancer properties in various cancers, including PDAC. This study aimed to evaluate the anticancer effects of cannabinoids, individually and in combination, and to elucidate their mechanisms of action in a murine PDAC model (KPC mice, KRASWT/G12D/TP53WT/R172H/Pdx1-Cre+/+) that mimics human disease. Additionally, the study explored the potential link between cannabinoid action, gut microbiota modulation, and bile acid (BA) metabolism. PDAC cell lines and KPC mice were treated with delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), either as monotherapy or in combination. Faecal pellets, caecal contents, plasma, and tissues were collected at the survival endpoint for analysis. BA profiling was performed using mass spectrometry, and the faecal microbiota was characterised by sequencing the V3-V4 region of the 16S rRNA gene. While CBD and THC synergistically reduced cell viability in PDAC cell lines, only CBD monotherapy improved survival in KPC mice. Extended survival with CBD was accompanied by changes in gut microbiota composition and BA metabolism, suggesting a possible association. Notably, the effects of CBD were different from those observed with THC alone or in combination with CBD. The study highlights a distinct role for CBD in altering BA profiles, suggesting these changes may predict responses to cannabidiol in PDAC models. Furthermore, the findings propose that targeting BA metabolism could offer a novel therapeutic strategy for PDAC. Full article

Background: Dyslipidemia and distorted fatty acid (FA) metabolism are frequent biochemical abnormalities associated with anorexia nervosa (AN). Gut microbiota is supposed to play an important role in the etiopathogenesis of AN. Apart from the digestive function of bile acids (BAs), these compounds have multiple metabolic functions due to the activation of specific receptors. Objective/aims: The aims of the study were to investigate biochemical measures, including plasma lipids (lipoproteins, respectively), fatty acid (FA) patterns, and the profile of plasma Bas, in AN patients and healthy controls (CON). Methods: Plasma phospholipid FA and BAs profiles were analyzed in 39 women with a restrictive type of AN (AN-R; median age 17 years) and in 35 CON women (median age 20 years). Results: Compared to CON, AN had an increased concentration of HDL-C, increased content of palmitic acid, and decreased proportion of linoleic acid. Moreover, AN had a drop in the level of the sum of PUFAn-6 and increased delta 9 desaturase activity for stearic acid. In AN, we found decreased levels of plasma tauroursodeoxycholic acid (TUDCA). In AN, concentrations of 22:5n-6, 16:0, 20:3n-6 and fat mass index were predic-tors of HDL-C levels (R² = 0.43). Conclusions: Patients with AN-R had an increased concentration of HDL-C, decreased levels of total PUFA n-6, and increased activity of D9D for stearic acid. Furthermore, AN exerted decreased levels of TUDCA. Therefore, a decreased level of TUDCA could potentially serve as a marker of AN. Full article

Background/Objectives: Metabolic dysregulation underlies a myriad of chronic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity, and bile acids emerge as an important mediator in their etiology. Weight control by improving diet quality is the standard of care in prevention and control of these metabolic diseases. Inclusion of pulses, such as common bean, is an affordable yet neglected approach to improving diet quality and metabolic outcomes. Thus, this study evaluated the possibility that common bean alters bile acid metabolism in a health-beneficial manner. Methods: Using biospecimens from several similarly designed studies, cecal content, feces, liver tissue, and plasma samples from C57BL/6 mice fed an obesogenic diet lacking (control) or containing cooked common bean were subjected to total bile acid analysis and untargeted metabolomics. RNA-seq, qPCR, and Western blot assays of liver tissue complemented the bile acid analyses. Microbial composition and predicted function in the cecal contents were evaluated using 16S rRNA gene amplicon and shotgun metagenomic sequencing. Results: Bean-fed mice had increased cecal bile acid content and excreted more bile acids per gram of feces. Consistent with these effects, increased synthesis of bile acids in the liver was observed. Microbial composition and capacity to metabolize bile acids were markedly altered by bean, with greater prominence of secondary bile acid metabolites in bean-fed mice, i.e., microbial metabolites of chenodeoxycholate/lithocholate increased while metabolites of hyocholate were reduced. Conclusions: In rendering mice resistant to obesogenic diet-induced MASLD and obesity, cooked bean consumption sequesters bile acids, increasing their hepatic synthesis and enhancing their diversity through microbial metabolism. Bean-induced changes in bile acid metabolism have potential to improve dyslipidemia. Full article

A high-fat diet leads to metabolic disturbances, which are important factors in the development of obesity. Gut microbial composition and diversity are altered by a high-fat diet. In general, a high-fat diet resulted in increased Firmicutes abundance and decreased alpha diversity. Bile acids (BAs) are involved in the digestion and absorption of fats in the small intestine and are also the metabolic substrates of microorganisms with bile salt hydrolase (BSH) activity. High-fat diets (HFDs) have been shown to alter gut microbiota composition and BA profiles in murine models. Similarly, probiotic supplementation reverses HFD-induced adverse effects. This review focuses on the energy composition characteristics of a high-fat diet and its effects on body weight, plasma lipid-related biochemical markers, changes in gut microbiome characteristics, and the important role of BAs. The regular mechanism by which a high-fat diet affects the intestinal microenvironment was attempted to be found. Full article

Objectives: Hyperlipidemia is a risk factor for various diseases. Identifying food components that can help reduce the levels of blood lipids, such as cholesterol and triglycerides, is a global research priority. It has been reported that 1-Kestose, a fructooligosaccharide, can reduce blood cholesterol and triglyceride levels in rats; however, the underlying mechanisms remain unclear. Therefore, we aimed to elucidate the effects of 1-kestose supplementation on lipid metabolism and the gut environment in rats. Methods: Twenty male Sprague–Dawley rats (age 8 weeks) were provided 1-kestose-containing water and were maintained for two weeks. After dissection, the blood components, hepatic gene expression, gut microbiota, and bile acid composition in the cecal contents of the rats were analyzed. Results: The 1-Kestose intake reduced plasma cholesterol and triglyceride levels. Additionally, an increase in cytochrome P450 family 7 subfamily A member 1 mRNA expression, a key gene for bile acid synthesis in the liver, and a decrease in lipid synthesis-related mRNA expression were observed. In the cecum, the levels of deconjugated bile acids, which are involved in the regulation of lipid synthesis, were increased. Furthermore, the 1-kestose intake altered the gut microbiota in the cecum, leading to an increase in the abundance of specific bacteria, such as Bifidobacterium, which are involved in the deconjugation of conjugated bile acids. Conclusions: The intake of 1-kestose alters the gut microbiota and bile acid metabolism in the cecum, potentially influencing lipid metabolism in the host. Full article

Background/Objectives: The transition from a non-lactating to a lactating state is a critical period for lipid metabolism in dairy cows. Danggui Buxue Tang (DBT), stimulating energy metabolism, ameliorates diseases related to lipid metabolism disorders and is expected to be an effective supplement for alleviating excessive lipid mobilisation in periparturient dairy cows. This study aimed to investigate the effects of supplemental DBT on serum biochemical indices, faecal microbial communities, and plasma metabolites in dairy cows. Methods: Thirty cows were randomly divided into three groups: H-DBT group, L-DBT group, and control group. DBT administration was started on the day of calving and continued once daily for seven days. Faecal and blood samples were collected on calving day, 7 days after calving, and 14 days after calving. The levels of serum biochemical indices were measured at three time points in the three groups using commercial kits. Cows in the H-DBT group and control group were selected for metabolome and 16S rRNA amplicon sequencing. Results: Our research shows that, in dairy cows 7 days postpartum, DBT significantly reduced serum 3-hydroxybutyric acid (BHB) concentrations and the number of cows with BHB concentrations ≥ 1 mmol/L. Additionally, DBT increased serum total cholesterol contents at both 7 and 14 days postpartum. Analysis of the microbiota community showed that DBT modulated the composition and structure of the hindgut microbiota. Metabolomic analysis revealed decreased plasma acetylcarnitine, 2-hydroxybutyric acid, and BHB levels 7 days postpartum, whereas the TCA cycle was enhanced. At 14 days postpartum, DBT altered the plasma bile acid profile, especially glycine-conjugated bile acids, including GCDCA, GUDCA, and GDCA. Correlation analyses showed that the relative abundances of Bacillus, Solibacillus, Dorea, and Romboutsia were strongly correlated with the differential metabolites, which is crucial for the beneficial effects of DBT. Conclusions: DBT improves energy status and lipid metabolism in postpartum dairy cows by modulating hindgut microbiota and serum lipid metabolites. Full article

Levodopa is the mainstay of treatments for Parkinson’s disease (PD), but large heterogeneity exists in patient response. Increasing evidence implicates bile acids (BAs) involved in the pathogenesis of PD. Furthermore, BAs have also participated in drug bioavailability. However, the impact of BAs on levodopa response (LR) has not been investigated. This study evaluated the association between fecal BAs and LR. Levodopa challenge test (LCT) was conducted in 92 PD patients to assess LR. A total of 36 fecal BAs and plasma levodopa concentrations were detected using LC-MS/MS. The difference of BAs between subgroups with bottom and top 30% LR were analyzed and fecal samples from the two groups were collected for metagenomic shotgun analysis. No fecal BAs were significantly correlated with LR, except for chenodeoxycholic acid-3-β-D-glucuronide (CDCA-3-β-glucuronide, R = −0.228, p-value = 0.039). We found no significant difference in BAs between subgroups with bottom and top 30% LR. What is more, no significant changes in bacterial species composition related to bile acids metabolism or in the proportional representation of genes encoding known bile acids enzymes were observed between the groups. Overall, our data do not support an association between fecal BAs and levodopa response in PD patients. More precise macro-metabolomic approaches are needed to reveal the potential association between gut microbial interactions and the treatment effect of levodopa. Full article

Pigs stand as a vital cornerstone in the realm of human sustenance, and the intricate composition of their intestinal microbiota wields a commanding influence over their nutritional and metabolic pathways. We employed multi-omic evaluations to identify microbial evidence associated with differential growth performance and metabolites, thereby offering theoretical support for the implementation of efficient farming practices for Tibetan pigs and establishing a robust foundation for enhancing pig growth and health. In this work, six Duroc × landrace × yorkshi (DLY) pigs and six Tibetan pigs were used for the experiment. Following humane euthanasia, a comprehensive analysis was undertaken to detect the presence of short-chain fatty acids (SCFAs), microbial populations, and metabolites within the colonic environment. Additionally, metabolites present within the plasma were also assessed. The outcomes of our analysis unveiled the key variables affecting the microbe changes causing the observed differences in production performance between these two distinct pig breeds. Specifically, noteworthy discrepancies were observed in the microbial compositions of DLY pigs, characterized by markedly higher levels of Alloprevotella and Prevotellaceae_UCG-003 (p < 0.05). These disparities, in turn, resulted in significant variations in the concentrations of acetic acid, propionic acid, and the cumulative SCFAs (p < 0.05). Consequently, the DLY pigs exhibited enhanced growth performance and overall well-being, which could be ascribed to the distinct metabolite profiles they harbored. Conversely, Tibetan pigs exhibited a significantly elevated relative abundance of the NK4A214_group, which consequently led to a pronounced increase in the concentration of L-cysteine. This elevation in L-cysteine content had cascading effects, further manifesting higher levels of taurine within the colon and plasma. It is noteworthy that taurine has the potential to exert multifaceted impacts encompassing microbiota dynamics, protein and lipid metabolism, as well as bile acid metabolism, all of which collectively benefit the pigs. In light of this, Tibetan pigs showcased enhanced capabilities in bile acid metabolism. In summation, our findings suggest that DLY pigs excel in their proficiency in short-chain fatty acid metabolism, whereas Tibetan pigs exhibit a more pronounced competence in the realm of bile acid metabolism. These insights underscore the potential for future studies to leverage these breed-specific differences, thereby contributing to the amelioration of production performance within these two distinct pig breeds. Full article

(1) Background: Probiotics in the form of nutritional supplements are safe and potentially useful for strategic application among endurance athletes. Bifidobacterium animalis lactis BL-99 (BL-99) was isolated from the intestines of healthy Chinese infants. We combined plasma-targeted metabolomics and fecal metagenomics to explore the effect of 8 weeks of BL-99 supplementation on cross-country skiers’ metabolism and sports performance. (2) Methods: Sixteen national top-level male cross-country skiers were recruited and randomly divided into a placebo group (C) and a BL-99 group (E). The participants took the supplements four times/day (with each of three meals and at 21:00) consistently for 8 weeks. The experiment was conducted in a single-blind randomized fashion. The subject’s dietary intake and total daily energy consumption were recorded. Blood and stool samples were collected before and after the 8-week intervention, and body composition, muscle strength, blood biochemical parameters, plasma-targeted metabolomic data, and fecal metagenomic data were then analyzed. (3) Results: The following changes occurred after 8 weeks of BL-99 supplementation: (a) There was no significant difference in the average total daily energy consumption and body composition between the C and E groups. (b) The VO_2max and 60°/s and 180°/s knee joint extensor strength significantly increased in both the C and E groups. By the eighth week, the VO_2max and 60 s knee-joint extensor strength were significantly higher in the E group than in the C group. (c) The triglyceride levels significantly decreased in both the C and E groups. In addition, the LDL-C levels significantly decreased in the E group. (d) The abundance of Bifidobacterium animalis increased two-fold in the C group and forty-fold in the E group. (e) Plasma-targeted metabolomic analysis showed that, after eight weeks of BL-99 supplementation, the increases in DHA, adrenic acid, linoleic acid, and acetic acid and decreases in glycocholic acid and glycodeoxycholic acid in the E group were significantly higher than those in the C group. (f) Spearman correlation analysis showed that there was a significant positive correlation between Bifidobacterium animalis’ abundance and SCFAs, PUFAs, and bile acids. (g) There was a significant correlation between the most significantly regulated metabolites and indicators related to sports performance and lipid metabolism. (4) Conclusions: Eight weeks of BL-99 supplementation combined with training may help to improve lipid metabolism and sports performance by increasing the abundance of Bifidobacterium, which can promote the generation of short-chain fatty acids and unsaturated fatty acids, and inhibit the synthesis of bile acids. Full article

Bile acids (BAs) and their signaling pathways have been identified as therapeutic targets for liver and metabolic diseases. We generated Cyp2c70^−/− (KO) mice that were not able to convert chenodeoxycholic acid into rodent-specific muricholic acids (MCAs) and, hence, possessed a more hydrophobic, human-like BA pool. Recently, we have shown that KO mice display cholangiopathic features with the development of liver fibrosis. The aim of this study was to determine whether BA sequestration modulates liver pathology in Western type-diet (WTD)-fed KO mice. The BA sequestrant colesevelam was mixed into the WTD (2% w/w) of male Cyp2c70^+/+ (WT) and KO mice and the effects were evaluated after 3 weeks of treatment. Colesevelam increased fecal BA excretion in WT and KO mice and reduced the hydrophobicity of biliary BAs in KO mice. Colesevelam ameliorated diet-induced hepatic steatosis in WT mice, whereas KO mice were resistant to diet-induced steatosis and BA sequestration had no additional effects on liver fat content. Total cholesterol concentrations in livers of colesevelam-treated WT and KO mice were significantly lower than those of untreated controls. Of particular note, colesevelam treatment normalized plasma levels of liver damage markers in KO mice and markedly decreased hepatic mRNA levels of fibrogenesis-related genes in KO mice. Lastly, colesevelam did not affect glucose excursions and insulin sensitivity in WT or KO mice. Our data show that BA sequestration ameliorates liver pathology in Cyp2c70^−/− mice with a human-like bile acid composition without affecting insulin sensitivity. Full article

Background: A mechanistic understanding of the effects of dietary treatment in irritable bowel syndrome (IBS) is lacking. Our aim was therefore to investigate how fermentable oligo- di-, monosaccharides, and polyols (FODMAPs) and gluten affected gut microbiota and circulating metabolite profiles, as well as to investigate potential links between gut microbiota, metabolites, and IBS symptoms. Methods: We used data from a double-blind, randomized, crossover study with week-long provocations of FODMAPs, gluten, and placebo in participants with IBS. To study the effects of the provocations on fecal microbiota, fecal and plasma short-chain fatty acids, the untargeted plasma metabolome, and IBS symptoms, we used Random Forest, linear mixed model and Spearman correlation analysis. Results: FODMAPs increased fecal saccharolytic bacteria, plasma phenolic-derived metabolites, 3-indolepropionate, and decreased isobutyrate and bile acids. Gluten decreased fecal isovalerate and altered carnitine derivatives, CoA, and fatty acids in plasma. For FODMAPs, modest correlations were observed between microbiota and phenolic-derived metabolites and 3-indolepropionate, previously associated with improved metabolic health, and reduced inflammation. Correlations between molecular data and IBS symptoms were weak. Conclusions: FODMAPs, but not gluten, altered microbiota composition and correlated with phenolic-derived metabolites and 3-indolepropionate, with only weak associations with IBS symptoms. Thus, the minor effect of FODMAPs on IBS symptoms must be weighed against the effect on microbiota and metabolites related to positive health factors. Full article