Therapeutic effect of yinchenhao decoction on cholelithiasis via mucin in the gallbladder and intestine.

Cholelithiasis is a common and frequently occurring disease worldwide that belongs to the category of jaundice in traditional Chinese medicine. Yinchenhao decoction (YD) consists of Artemisia capillaris Thunb., Gardenia jasminoides J.Ellis, and Rheum palmatum L., and is traditionally used to treat jaundice, which has a significant therapeutic effect on cholelithiasis. Our study aimed to investigate the pathological mechanism of cholelithiasis and the therapeutic mechanism of YD via mucin in the gallbladder and intestine. YD was prepared and analyzed using HPLC. The supersaturation stability experiment was designed by the solvent-shift method. The cell transport experiment was conducted by coculture monolayers. The animal experiment was performed using a cholelithiasis model with a high-cholesterol diet. The related indicators were detected by automatic biochemical analyzer, PCR, western blot, or ELISA. Statistics were analyzed using χ2-tests and t-tests. As the results, in cholelithiasis, MUC5AC highly expressed in the gallbladder shortened cholesterol supersaturation and promoted cholesterol crystallization via the inflammatory cytokine signaling pathway; MUC2 highly expressed in the small intestine prolonged cholesterol supersaturation and promoted cholesterol absorption via the inflammatory cytokine signaling pathway. YD inhibited mucin expression in the gallbladder and intestine in a concentration-dependent manner for cholelithiasis treatment by inhibiting the inflammatory cytokine signaling pathway, which was attributed to the active components, including chlorogenic acid, geniposide, and rhein.

Multi-omics approach to study the dual effects of novel proteins on the intestinal health of juvenile largemouth bass (Micropterus salmoides) under an alternate feeding strategy.

Introduction: In an effort to minimize the usage of fishmeal in aquaculture, novel protein diets, including Tenebrio molitor, cottonseed protein concentrate, Clostridium autoethanogenum, and Chlorella vulgaris were evaluated for their potential to replace fishmeal. Nevertheless, comprehensive examinations on the gut health of aquatic animals under an alternate feeding strategy when fed novel protein diets are vacant. Methods: Five isonitrogenous and isolipidic diets containing various proteins were manufactured, with a diet consisting of whole fishmeal serving as the control and diets containing novel proteins serving as the experimental diets. Largemouth bass (Micropterus salmoides) with an initial body weight of 4.73 ± 0.04g employed as an experimental animal and given these five diets for the first 29 days followed by a fishmeal diet for the next 29 days. Results: The results of this study demonstrated that the growth performance of novel protein diets in the second stage was better than in the first stage, even though only the C. vulgaris diet increased antioxidant capacity and the cottonseed protein concentrate diet decreased it. Concerning the intestinal barriers, the C. autoethanogenum diet lowered intestinal permeability and plasma IL-1ß/TNF-α. In addition, the contents of intestinal immunological factors, namely LYS and sIgA-like, were greater in C. vulgaris than in fishmeal. From the data analysis of microbiome and metabolome, the levels of short chain fatty acids (SCFAs), anaerobic bacteria, Lactococcus, and Firmicutes were significantly higher in the C. autoethanogenum diet than in the whole fishmeal diet, while the abundance of Pseudomonas, aerobic bacteria, Streptococcus, and Proteobacteria was lowest. However, no extremely large differences in microbiota or short chain fatty acids were observed between the other novel protein diets and the whole fishmeal diet. In addition, the microbiota were strongly connected with intestinal SCFAs, lipase activity, and tight junctions, as shown by the Mantel test and Pearson's correlation. Discussion: Taken together, according to Z-score, the ranking of advantageous functions among these protein diets was C. autoethanogenum diet > C. vulgaris diet > whole fishmeal diet > cottonseed protein concentrate > T. molitor diet. This study provides comprehensive data illustrating a mixed blessing effect of novel protein diets on the gut health of juvenile largemouth bass under an alternate feeding strategy.

Dietary Zinc Glycine Supplementation Improves Tibia Quality of Meat Ducks by Modulating the Intestinal Barrier and Bone Resorption.

Leg problems characterized by gait abnormity and bone structure destruction are associated with a high risk of fractures and continuous pain in poultry. Zinc (Zn) acts a pivotal part in normal bone homeostasis and has proven to be highly effective in alleviating leg problems. Therefore, the effects of graded concentration of Zn on bone quality were evaluated in this study. A total of 512 1-d-old male ducks were fed 4 basal diets added 30 mg/kg Zn, 60 mg/kg Zn, 90 mg/kg Zn, and 120 mg/kg Zn as Zn glycine for 35 d. Tibia Zn content, ash percentage, and breaking strength linearly increased with dietary elevated Zn level (P < 0.05). Broken-line analysis revealed that the recommended level of Zn from Zn glycine was 55.13 mg/kg and 64.48 mg/kg based on tibia ash and strength, respectively. To further confirm the role of dietary Zn glycine addition on bone characteristics, data from birds fed either 60 mg/kg Zn as Zn sulfate (ZnSO4), 30 mg/kg Zn, or 60 mg/kg Zn in the form of Zn glycine indicated that birds given 60 mg/kg Zn from Zn glycine diet exhibited higher tibia ash, strength, and trabecular volume compared to those fed the 30 mg/kg Zn diet (P < 0.05). Dietary 60 mg/kg Zn as Zn glycine addition decreased intestinal permeability, upregulated the mRNA expression of tight junction protein, and increased the abundance of Lactobacillus and Bifidobacterium, which was companied by declined the level of inflammatory cytokines in both the ileum and bone marrow. Regarding bone turnover, the diet with 60 mg/kg Zn from Zn glycine induced osteoprotegerin expression and thus decreased osteoclast number and serum bone resorption biomarker levels including serum tartrate-resistant acid phosphatase activity and C-terminal cross-linked telopeptide of type I collagen level when compared to 30 mg/kg Zn diet (P < 0.05). Except for the upregulation in runt-related transcription factor 2 transcription, the experimental treatments did not apparently change the bone formation biomarker contents in serum. Additionally, Zn glycine displayed a more efficient absorption rate, evidenced by higher serum Zn level, and thus had potentially greater a protective role in the intestine barrier and tibia mass as compared to ZnSO4. Collectively, the dietary supplementation of 60 mg/kg in the form of Zn glycine could suppress bone resorption mediated by osteoclast and consequently improve tibial quality of meat ducks, in which enhanced intestinal integrity and optimized gut microbiota might be involved.

Potential of Nutraceutical Supplementation in the Modulation of White and Brown Fat Tissues in Obesity-Associated Disorders: Role of Inflammatory Signalling.

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.

Dietary supplementation with Bacillus subtilis DSM 32315 alters the intestinal microbiota and metabolites in weaned piglets.

AIM: The study was conducted to investigate the effects of dietary Bacillus subtilis (BS) DSM 32315 on the intestinal microbiota composition and metabolites of weaned pigs. METHODS AND RESULTS: Sixty-four piglets were allocated to two groups (control and BS), each group including eight replicates with four piglets. Dietary BS DSM 32315 increased (P < 0·05) the abundances of jejunal Leucobacter and Cupriavidus, ileal Thermus, Coprococcus and Bifidobacterium, as well as colonic Succiniclasticum; and increased the concentrations of ileal straight-chain fatty acids, colonic propionate, branched-chain fatty acids (BCFAs), and tyramine, but decreased (P < .05) the colonic indole concentration. The ileal and colonic microbial community structure tended to cluster into two groups. LEfSe analysis identified five microbial biomarkers in jejunum and eight biomarkers in ileum in the BS group, and three biomarkers in colon in the control group. The ileal Bifidobacterium abundance was positively correlated (P < 0·05) with isovalerate concentration, while the colonic Actinobacteria and Lactobacillus abundances were negatively correlated (P < 0·05) with indole concentration. CONCLUSION: These findings suggest that dietary supplementation with BS DSM 32315 could alter the diversity, composition, and metabolites of intestinal microbiota in weaned piglets. SIGNIFICANCE AND IMPACT OF THE STUDY: Weaned piglets are often accompanied with impaired gastrointestinal tract and intestinal disorder affecting their growth. This study demonstrated that dietary BS DSM 32315 presented a beneficial role in gut health via regulating intestinal microbiota composition and metabolites.

DNA damage and health effects in juvenile haddock (Melanogrammus aeglefinus) exposed to PAHs associated with oil-polluted sediment or produced water.

The research objective was to study the presence of DNA damages in haddock exposed to petrogenic or pyrogenic polyaromatic hydrocarbons (PAHs) from different sources: 1) extracts of oil produced water (PW), dominated by 2-ring PAHs; 2) distillation fractions of crude oil (representing oil-based drilling mud), dominated by 3-ring PAHs; 3) heavy pyrogenic PAHs, mixture of 4/5/6-ring PAHs. The biological effect of the different PAH sources was studied by feeding juvenile haddock with low doses of PAHs (0.3-0.7 mg PAH/kg fish/day) for two months, followed by a two-months recovery. In addition to the oral exposure, a group of fish was exposed to 12 single compounds of PAHs (4/5/6-ring) via intraperitoneal injection. The main endpoint was the analysis of hepatic and intestinal DNA adducts. In addition, PAH burden in liver, bile metabolites, gene and protein expression of CYP1A, GST activity, lipid peroxidation, skeletal deformities and histopathology of livers were evaluated. Juvenile haddock responded quickly to both intraperitoneal injection and oral exposure of 4/5/6-ring PAHs. High levels of DNA adducts were detected in livers three days after the dose of the single compound exposure. Fish had also high levels of DNA adducts in liver after being fed with extracts dominated by 2-ring PAHs (a PW exposure scenario) and 3-ring PAHs (simulating an oil exposure scenario). Elevated levels of DNA adducts were observed in the liver of all exposed groups after the 2 months of recovery. High levels of DNA adduct were found also in the intestines of individuals exposed to oil or heavy PAHs, but not in the PW or control groups. This suggests that the intestinal barrier is very important for detoxification of orally exposures of PAHs.

Structural features of bovine colostral immunoglobulin that confer proteolytic stability in a simulated intestinal fluid.

Bovine colostral antibodies, purified from cow's milk produced immediately after calving, have enhanced resistance to degradation by intestinal proteases relative to antibodies from human or bovine serum, making them of particular interest as orally administered therapeutic agents. However, the basis of this resistance is not well defined. We evaluated the stability of AVX-470, a bovine colostral anti-tumor necrosis factor (TNF) polyclonal antibody used in early clinical studies for treatment of ulcerative colitis, using conditions that mimic the human small intestine. AVX-470 was degraded ∼3 times more slowly than human IgG antibodies or infliximab (a monoclonal mouse-human chimeric IgG). Bovine IgG1 antibodies, the primary component of AVX-470, were slowly cleaved to F(ab')2 fragments. In contrast, bovine IgG2 and human IgG1 antibodies were cleaved rapidly into Fab and smaller fragments, pointing to specific regions where additional stability might be gained. Infliximab was modified to incorporate the sequences from these regions, including the bovine IgG1 hinge region and a predicted disulfide bonding motif linking the upper hinge region, the CH1 domain, and the light chain. This infliximab-bovine IgG1 chimera (bovinized infliximab) retained the antigen binding and neutralization activity of the WT sequence but was degraded 9-fold more slowly than the unmodified infliximab. This remarkable increase in stability with as few as 18 amino acid substitutions suggests that this bovinization process is a means to enable oral delivery of proven therapeutic antibodies as well as novel antibodies to targets that have been previously inaccessible to therapies delivered by injection.

Physicochemical and swelling properties of composite gel microparticles based on alginate and callus cultures pectins with low and high degrees of methylesterification.

Composite gel microparticles based on alginate and callus culture pectins with low and high degrees of methylesterification or apple pectin were produced. By varying the chemical composition of the pectic samples and the ratio of alginate to pectin, the gel strength, morphology, and swelling properties of composite microparticles can be altered. The inclusion of increasing concentrations of alginate in gel formulations promoted an increase in the microparticle gel strength and the formation of a smoother surface microrelief independently of the pectin chemical composition. Microparticles based on the pectin with a low degree of methylesterification (DM) and a higher concentration of alginate exhibited an increased swelling degree in the simulated digestive fluids. Microparticles based on the pectin with high DM and low alginate concentration were destroyed in the simulated intestinal fluid within 1 h due to the low Ca2+ content, gel strength, and grooved and rough surface of these microparticles. An increase in alginate concentration of gel formulations based on pectin with high DM led to increased stability of the microparticles in the simulated intestinal and colonic fluids due to increased Ca2+ content, microparticle gel strength and degree of crosslinking.

DHA and its derived lipid mediators MaR1, RvD1 and RvD2 block TNF-α inhibition of intestinal sugar and glutamine uptake in Caco-2 cells.

Tumor necrosis factor-alfa (TNF-α) is a pro-inflammatory cytokine highly-involved in intestinal inflammation. Omega-3 polyunsaturated fatty acids (n3-PUFAs) show anti-inflammatory actions. We previously demonstrated that the n3-PUFA EPA prevents TNF-α inhibition of sugar uptake in Caco-2 cells. Here, we investigated whether the n3-PUFA DHA and its derived specialized pro-resolving lipid mediators (SPMs) MaR1, RvD1 and RvD2, could block TNF-α inhibition of intestinal sugar and glutamine uptake. DHA blocked TNF-α-induced inhibition of α-methyl-D-glucose (αMG) uptake and SGLT1 expression in the apical membrane of Caco-2 cells, through a pathway independent of GPR120. SPMs showed the same preventive effect but acting at concentrations 1000 times lower. In diet-induced obese (DIO) mice, oral gavage of MaR1 reversed the up-regulation of pro-inflammatory cytokines found in intestinal mucosa of these mice. However, MaR1 treatment was not able to counteract the reduced intestinal transport of αMG and SGLT1 expression in the DIO mice. In Caco-2 cells, TNF-α also inhibited glutamine uptake being this inhibition prevented by EPA, DHA and the DHA-derived SPMs. Interestingly, TNF-α increased the expression in the apical membrane of the glutamine transporter B0AT1. This increase was partially blocked by the n-3 PUFAs. These data reveal DHA and its SPMs as promising biomolecules to restore intestinal nutrients transport during intestinal inflammation.

Study of Metal-Metal Interactions and Their Biomarkers Using an Intestinal Human Cell Line.

From the time of dietary intake to their utilization, the number of important interactions occurs among mineral elements, which can affect their bioavailability because of similarity in physicochemical properties and common absorptive pathways. However, the studies that have analyzed the interactions among copper, iron, and zinc have conflicting results and need further exploration. HT-29 cells grown to confluence in 6-well plates were incubated with increasing concentrations (0 to 200 µM) of Cu, Fe, and Zn for 3 and 6 h for uptake studies. Interaction studies involved measuring the uptake of metal in the presence of 0:1-4:1 ratio of the other metal for 3 h using atomic absorption spectrophotometer. The concentration of metal biomarkers and cytokines was also measured in the cell lysate following extracellular supplementation. The presence of 50 µM Zn significantly decreased (P < 0.05) cellular Cu uptake in HT-29 cells at 0.5:1 Cu:Zn ratio and also the cellular Fe uptake at the ratios 0.5:1, 2:1, and 4:1 Fe:Zn. The presence of 50 µM Fe significantly (P < 0.05) decreased cellular Cu uptake at the ratios 1:1, 2:1, and 4:1 Cu:Fe. The concentration of metallothionein responded significantly (P < 0.05) to changes in extracellular Zn concentration (supplementation and depletion). There was a decrease in concentration of IL-1ß and TNF-α (P < 0.05) with an increasing extracellular concentration of Cu and Fe. The results of the study indicated that the presence of one mineral in the diet and multi mineral supplement may influence the bioavailability of the other mineral. Copper and iron may find application in promoting gut health.

MALDI-Mass Spectrometry Imaging to Investigate Lipid and Bile Acid Modifications Caused by Lentil Extract Used as a Potential Hypocholesterolemic Treatment.

This paper reports matrix-assisted laser desorption/ionization mass spectrometry imaging to investigate systematic effects of a lentil extract treatment to lower cholesterol levels. For this purpose, mass spectrometry imaging was used to spatially investigate modifications in the lipid composition and cholesterol levels in the brain, liver, and intestines as well as bile acids in the liver and intestine of rats treated with lentil extract. Neither the lipid composition nor cholesterol levels in the brain samples were found to be significantly different between the treated and not-treated animal groups. The hypercholesterolemic livers showed signs of steatosis (lipid marker PG 36:4), but no modifications in bile acid, cholesterol, and lipid composition. We found significant differences (AUC > 0.75) in the intestines regarding bile acid and lipid composition after treatment with the lentil extract. The treated rats showed a decreased reabsorption (increased excretion) of ursodeoxycholic acid, deoxycholic acid, and chenodeoxycholic acid and an increased deconjugation of taurine-conjugated bile acids (taurochenodeoxycholic acid, taurodeoxycholic acid, taurocholic acid, and 3-keto-taurocholic acid). This indicates that the lentil extract lowers the total cholesterol level in two synergic ways: (i) it increases the excretion of bile acids; hence, new bile acids are produced in the liver from serum cholesterol and (ii) the prebiotic effect leads to free taurine which upregulates the de novo synthesis of bile acid from cholesterol while activating LDL receptors. We demonstrate here that mass spectrometry imaging is a valuable tool for a better understanding of the effects of treatments such as for the synergistic cholesterol-lowering effect of the lentil extract.

Inclusion of IgY in a dog's diet has moderate impact on the intestinal microbial fermentation.

AIMS: This study aimed to evaluate the impact of immunoglobulin Y (IgY) in a diet on the systemic health and the gastrointestinal tract (GIT) of dogs. METHODS AND RESULTS: Sixteen healthy 11-month-old Beagle dogs were distributed at random (eight animals per treatment) in two treatments groups: control (0 g kg-1 IgY) and test (2 g IgY per day). The animals were evaluated on days 0 and 40 for a complete blood count (CBC) and biochemical profiles (ALT, ALP, creatinine and urea). Faecal samples were collected from days 35 to 40 to measure nutrient digestibility, faecal characteristics, sialic acid, intestinal microbiota composition and microbial metabolites. The CBC, biochemical profiles, apparent nutrient digestibility and faecal characteristics did not differ between the two treatment groups (P > 0·05). Dog faeces that received IgY were characterized by lower sialic acid and n-valeric concentration, as well as an increase in n-butyric concentration, in contrast to dogs fed a diet without IgY (P < 0·05). The other microbial faecal metabolites did not differ between the two treatment groups (P > 0·05). There tended to be an increase in the copy number of Clostridium cluster XIVa (Clostridium coccoides group) in the IgY group in contrast to the control group (P = 0·07). The other bacteria analysed did not differ between the treatment groups (P > 0·05). The colonic pH in the IgY group was lower than in control group (P < 0·05). CONCLUSIONS: The addition of IgY in the diet of healthy dogs maintains the microbial balance and has an interesting effect on microbial metabolites. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of IgY, antibodies produced by laying hens, in animal feed is an alternative for the prevention and treatment of intestinal diseases in companion animals.

Reduced intestinal FADS1 gene expression and plasma omega-3 fatty acids following Roux-en-Y gastric bypass.

BACKGROUND & AIMS: Roux-en-Y gastric bypass (RYGB) limits food ingestion and may alter the intestinal expression of genes involved in the endogenous synthesis of polyunsaturated fatty acids (PUFAs). These changes may decrease the systemic availability of bioactive PUFAs after RYGB. To study the impact of RYGB on the dietary ingestion and plasma concentration of PUFAs and on the intestinal expression of genes involved in their endogenous biosynthesis in severely obese women with type 2 diabetes. METHODS: Before, and 3 and 12 months after RYGB, obese women (n = 20) self-reported a seven-day dietary record, answered a food frequency query and provided plasma samples for alpha-linolenic (ALA), eicosapentaenoic (EPA), docosahexaenoic (DHA) and arachidonic (ARA) acid assessment by gas chromatography. Intestinal biopsies (duodenum, jejunum and ileum) were collected through double-balloon endoscopy before and 3 months after RYGB for gene expression analysis by microarray (Human GeneChip 1.0 ST array) and RT-qPCR validation. RESULTS: Compared to the preoperative period, patients had decreased intakes of PUFAs, fish and soybean oil (p < 0.05) and lower plasma concentrations of ALA and EPA (p < 0.001) 3 and 12 months after RYGB. FADS1 gene expression was lower in duodenum (RT-qPCR fold change = -1.620, p < 0.05) and jejunum (RT-qPCR fold change = -1.549, p < 0.05) 3 months following RYGB, compared to before surgery. CONCLUSION: RYGB decreased PUFA ingestion, plasma ALA and EPA levels, and intestinal expression of FADS1 gene. The latter encodes a key enzyme involved in endogenous biosynthesis of PUFAs. These data suggest that supplementation of omega-3 PUFAs may be required for obese patients undergoing RYGB. Clinical Trial Registry number and website: www.clinicaltrials.gov - NCT01251016; Plataforma Brasil - 19339913.0.0000.0068.

Stability of Vegetal Diamine Oxidase in Simulated Intestinal Media: Protective Role of Cholic Acids.

Food biogenic amines, in particular, histamine, are often responsible for various enteric and vascular dysfunctions. Several years ago, the oral administration of copper-containing diamine oxidase (DAO), also called histaminase, able to oxidatively deaminate biogenic amines, had been suggested as a food supplement to control food allergy and enteric dysfunctions. This report is aimed to generate a global image on the behavior of orally administrated DAO dosage forms in the intestinal tract. The catalytic stability of DAO from Lathyrus sativus seedlings in various simulated intestinal media with different pH and containing different association of cholic acids, pancreatic proteases, bicarbonate, lipids, or alcohol was investigated. Cholic acids and lipids protected the enzyme in the simulated intestinal fluids. However, they were not able to protect against the inhibitory effect of 24-36% (v/v) ethanol. These observations may be relevant for oral administration of enzymes as food supplements or therapeutic bioactive agents.

Supplemental Bacillus subtilis DSM 32315 manipulates intestinal structure and microbial composition in broiler chickens.

Knowledge about the modulation of gut microbiota improves our understanding of the underlying mechanism by which probiotic treatment benefits the chickens. This study examined the effects of Bacillus subtilis DSM 32315 on intestinal structure and microbial composition in broilers. Broiler chicks were fed basal diets without or with B. subtilis supplementation (1.0 × 109 spores/kg of diet). Supplemental B. subtilis increased average body weight and average daily gain, as well as elevated villus height and villus height to crypt depth ratio of ileum in broilers. Multi-dimension analysis showed a certain degree of separation between the cecal microbiota from treatment and control groups. Increased Firmicutes abundance and reduced Bacteroidetes abundance in cecum were observed responded to B. subtilis addition, which also increased the abundances of Christensenellaceae and Caulobacteraceae, and simultaneously decreased the abundances of potentially harmful bacteria such as Vampirovibrio, Escherichia/Shigella and Parabacteroides. Network analysis signified that B. subtilis addition improved the interaction pattern within cecal microbiota of broilers, however, it exerted little influence on the metabolic pathways of cecal microbiota by comparison of the functional prediction of metagenomes. In conclusion, supplemental B. subtilis DSM 32315 improved growth performance and intestinal structure of broilers, which could be at least partially responsible by the manipulation of cecal microbial composition.

Metabolomics and Lipidomics Approaches in the Science of Probiotics: A Review.

The intestinal microflora plays important roles in the health of the host, such as nutrient processing and the modulation of intestinal immune responses. The constituents of the diet greatly affect the composition of the microbiota and its metabolites. The human intestinal microbiota is made up of around 100 trillion microbial cells encompassing at least 300 species. Consuming probiotics may lead to changes in the intestinal microflora that influence host health. Metabolomics is a powerful tool for revealing metabolic changes in biofluids, tissues, and organs of hosts induced by the consumption of probiotics, and lipidomics in particular is a technical approach that focuses on the analysis of lipids in various cells and biofluids. Metabolomics and lipidomics have been used to investigate intracellular and extracellular metabolites as well as for the nontargeted profiling and fingerprinting of metabolites. Based on metabolomics and lipidomics investigations, we reviewed the effects of consuming probiotics on metabolic profiles in controlled intestinal environments. We also discuss the associations between metabolic changes and human diseases after consuming probiotics in uncontrolled intestinal environments. In addition, we review the metabolic changes that take place within the food matrix during probiotic fermentation.

Pharmacokinetics and Bioavailability of the Isoflavones Formononetin and Ononin and Their in Vitro Absorption in Ussing Chamber and Caco-2 Cell Models.

Formononetin and its glycoside ononin are bioactive isoflavones widely present in legumes. The present study investigated the pharmacokinetics, bioavailability, and in vitro absorption of formononetin and ononin. After an oral administration to rats, formononetin showed a higher systemic exposure over ononin. The oral bioavailability of formononetin and ononin were 21.8% and 7.3%, respectively. Ononin was more bioavailable than perceived, and its bioavailability reached 21.7% when its metabolite formononetin was taken into account. Both formononetin and ononin exhibited better absorption in large intestine segments than that in small intestine segments. Formononetin displayed a better permeability in all intestinal segments over ononin. Transport of formononetin across Caco-2 cell monolayer was mainly through passive diffusion, while ononin was actively pumped out by MRP2 but not P-gp. The results provide evidence for better understanding of the pharmacological actions of formononetin and ononin, which advocates more in vivo evaluations or human trials.

Inhibitory Influence of Panax notoginseng Saponins on Aspirin Hydrolysis in Human Intestinal Caco-2 Cells.

Herb-drug interactions are important safety concerns in clinical practice. The interactions occur firstly in the intestinal absorption for orally administered drugs. Aspirin and Panax notoginseng saponins (PNS)-based drugs are often combined in China to prevent larger-artery atherosclerosis. Here, we aimed to characterize the aspirin transport across Caco-2 cell monolayers, a model of the intestinal absorption, and further to evaluate the influence of PNS on aspirin hydrolysis and the relating mechanisms. Transcellular transport of aspirin and the influence of PNS were explored using Caco-2 cell monolayers. The protein expression of human carboxylesterase 1 (hCE1) and hCE2 in Caco-2 cells after PNS treatment was analyzed by ELISA, and the mRNA level were determined by qRT-PCR. In the study, Caco-2 cells showed high level of hydrolase activity, and most aspirin was hydrolyzed inside the cells during the transport process. Interestingly, PNS were demonstrated to inhibit the esterase activities responsible for aspirin hydrolysis in Caco-2 cells. PNS could also decrease the protein expression of hCE1 and hCE2, whereas exhibited minor effect on the mRNA expression. These results indicated that oral administration of PNS-based drugs might inhibit the hydrolysis of aspirin during intestinal absorption thus promoting its bioavailability.

Bioavailability and metabolism of rosemary infusion polyphenols using Caco-2 and HepG2 cell model systems.

BACKGROUND: Rosmarinus officinalis is an aromatic plant used in folk medicine as a result of the therapeutic properties associated with its phenolic composition, being rich in rosmarinic acid (RA) and caffeic acid (CA). To better understand the bioactivity of these compounds, their absorption and metabolism were assessed in human Caco-2 and HepG2 cells, as small intestine and liver models, respectively, using RA and CA standards, as well as a rosemary infusion and ferulic acid (FA). RESULTS: Test compounds were partially up-taken and metabolized by Caco-2 and HepG2 cells, although a higher metabolization rate was observed after hepatic incubation compared to intestinal incubation. CA was the compound best absorbed followed by RA and FA, showing metabolites percentages of 30.4%, 11.8% and 4.4% in Caco-2 and 34.3%, 10.3% and 3.2% in HepG2 cells, respectively. RA in the rosemary infusion showed improved bioavailability compared to pure RA. Methyl derivatives were the main metabolites detected for CA and RA after intestinal and hepatic metabolism, followed by methyl-glucuronidates and glucuronidates. RA was also minimally hydrolyzed into CA, whereas FA only was glucuronidated. Rosemary polyphenols followed the same biotransformation pathways as the standards. In addition, phase II derivatives of luteolin were observed. CONCLUSION: Rosemary polyphenols are partially metabolized in both the intestine and liver. © 2018 Society of Chemical Industry.

Effects of lysolecithin supplementation in low-energy diets on growth performance, nutrient digestibility, viscosity and intestinal morphology of broilers.

1. The study aimed to investigate the effect of lysolecithin supplementation in low-energy diets on growth, nutrient digestibility and intestinal mucosa characteristics of broilers. 2. A total of 800 one-d-old Ross 308 broiler chickens were assigned to 4 dietary treatments consisting of 10 replicates of 20 broilers each. Broilers were fed with 4 different diets: (i) HE: positive control group broilers received a diet with unaltered energy; (ii) LE: negative control group broilers received a diet with lower energy of about 0.27 MJ/kg; (iii) LElys500: broilers received a diet similar to LE supplemented with 500 g/tn lysolecithin product (Lysoforte Booster DryTM); and (iv) LElys300: broilers received a diet similar to LE supplemented with 300 g/tn lysolecithin product. The experimental period was 42 d. 3. Body weight gain in treatments HE was higher than LE during the overall experimental period, while LElys500 and LElys300 had intermediate values. Feed conversion ratio was lower in HE and LElys500 than LE group, while the LElys300 had intermediate values. Fat digestibility was improved in both LElys 500 and LElys300 compared to the HE group. Apparent metabolisable energy (AMEn) was higher in HE, LElys500 and LElys300 than LE. Ileum viscosity at 42 d was also affected, being higher in LE group compared to HE. At 28 d mucosal thickness was lower both in LElys500 and LElys300 compared to HE and LE, while no difference occurred between treatment proliferation patterns of duodenal epithelial cells. 4. These findings indicated that lysolecithin supplementation at 500 g/tn of feed in low-energy diets maintained broiler performance. Supplementation of reformulated low-energy diets induced an increase in digesta viscosity. Lysolecithin supplementation resulted in variable alterations in the duodenum mucosal morphology.