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The fate of dietary protein in the gut is determined by microbial and host digestion and utilization. Fermentation of proteins generates bioactive molecules that have wide-ranging health effects on the host. The type of protein can affect amino acid absorption, with animal proteins generally being more efficiently absorbed compared with plant proteins. In contrast to animal proteins, most plant proteins, such as pea protein, are incomplete proteins. Pea protein is low in methionine and contains lower amounts of branched-chain amino acids (BCAAs), which play a crucial role in muscle health. We hypothesized that probiotic supplementation results in favorable changes in the gut microbiota, aiding the absorption of amino acids from plant proteins by the host. Fifteen physically active men (24.2 ± 5.0 years; 85.3 ± 12.9 kg; 178.0 ± 7.6 cm; 16.7 ± 5.8% body fat) co-ingested 20 g of pea protein with either AminoAlta™, a multi-strain probiotic (5 billion CFU L. paracasei LP-DG® (CNCM I-1572) plus 5 billion CFU L. paracasei LPC-S01 (DSM 26760), SOFAR S.p.A., Italy) or a placebo for 2 weeks in a randomized, double-blind, crossover design, separated by a 4-week washout period. Blood samples were taken at baseline and at 30-, 60-, 120-, and 180-min post-ingestion and analyzed for amino acid content. Probiotic administration significantly increased methionine, histidine, valine, leucine, isoleucine, tyrosine, total BCAA, and total EAA maximum concentrations (Cmax) and AUC without significantly changing the time to reach maximum concentrations. Probiotic supplementation can be an important nutritional strategy to improve post-prandial changes in blood amino acids and to overcome compositional shortcomings of plant proteins. ClinicalTrials.gov Identifier: ISRCTN38903788

BACKGROUND: The potential health benefits of curcumin are limited by its poor solubility, low absorption from the gut, rapid metabolism and rapid systemic elimination. The purpose of this study was the comparative measurement of the increases in levels of curcuminoids (curcumin, demethoxycurcumin, bisdemethoxycurcumin) and the metabolite tetrahydrocurcumin after oral administration of three different curcumin formulations in comparison to unformulated standard. METHODS: The relative absorption of a curcumin phytosome formulation (CP), a formulation with volatile oils of turmeric rhizome (CTR) and a formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives and natural antioxidants (CHC) in comparison to a standardized curcumin mixture (CS) was investigated in a randomized, double-blind, crossover human study in healthy volunteers. Samples were analyzed by HPLC-MS/MS. RESULTS: Total curcuminoids appearance in the blood was 1.3-fold higher for CTR and 7.9-fold higher for CP in comparison to unformulated CS. CHC showed a 45.9-fold higher absorption over CS and significantly improved absorption over CP (5.8-fold) and CTR (34.9-fold, all p < 0.001). CONCLUSION: A formulation of curcumin with a combination of hydrophilic carrier, cellulosic derivatives and natural antioxidants significantly increases curcuminoid appearance in the blood in comparison to unformulated standard curcumin CS, CTR and CP.

PURPOSE : The original aim of the study was to determine, in a double-blind 3-arm crossover human trial (n = 7), the effect of supplemental levels of iron (25 mg) and zinc (30 mg) on β-carotene (synthetic) bioavailability (10 h postprandial). However, despite the high dose of supplemental β-carotene (15 mg) consumed with the high fat (18 g), dairy-based breakfast test meal, there was a negligible postprandial response in plasma and triglyceride rich fraction β-carotene concentrations. We then systematically investigated the possible reasons for this low bioavailability of β-carotene. METHODS : We determined (1) if the supplemental β-carotene could be micellised and absorbed by epithelial cells, using a Caco-2 cell model, (2) if the fat from the test meal was sufficiently bioavailable to facilitate β-carotene bioavailability, (3) the extent to which the β-carotene could have been metabolised and converted to retinoic acid/retinol and (4) the effect of the test meal matrix on the β-carotene bioaccessibility (in vitro digestion) and Caco-2 cellular uptake. RESULTS : We found that (1) The supplemental β-carotene could be micellised and absorbed by epithelial cells, (2) the postprandial plasma triacylglycerol response was substantial (approximately 75–100 mg dL−1 over 10 h), indicating sufficient lipid bioavailability to ensure β-carotene absorption, (3) the high fat content of the meal (approximately 18 g) could have resulted in increased β-carotene metabolism, (4) β-carotene bioaccessibility from the dairy-based test meal was sixfold lower (p < 0.05) than when digested with olive oil. CONCLUSION : The low β-carotene bioavailability is probably due to a combination of the metabolism of β-carotene to retinol by BCMO1 and interactions of β-carotene with the food matrix, decreasing the bioaccessibility. TRAIL REGISTRATION : The human trail was retrospectively registered (ClinicalTrail.gov ID: NCT05840848).

Background: Immune activation contributes to the persistent state of inflammation associated with metabolic dysfunction in obesity. The specific immune receptors that sense metabolic stress signals and trigger inflammation are nevertheless largely unknown, and little is known on inflammatory and immune gene regulation in obesity. Methods: The study includes a cross-sectional and a longitudinal arm. Forty children and adolescents were enrolled: 22 obese subjects and 18 age-matched normal weight controls. Obese subjects participated in an 18-month therapeutic protocol, based on intensive lifestyle modification (dietary regimen, physical activity and behavioral interventions). Expression of genes involved in the inflammasome pathway, plasma concentration of the inflammasome-associated pro-inflammatory cytokines (interleukin (IL)-1β and IL-18) and indexes of microbial translocation (lipopolysaccharide (LPS), soluble CD14 (sCD14) and intestinal fatty acid-binding protein) were analyzed at baseline in obese subjects compared with controls, and after 18 months in obese subjects. Results: Cross-sectional analyses showed that the LPS-induced expression of genes involved in inflammasome (NLRP3, caspase 5 and NAIP), Nod-like receptors (NLRX1 and NOD1), downstream signaling (P2RX7, RAGE, RIPk2, TIRAP and BIRC2) and effector molecules (IFN-γ, IL-12β, IL-1β, CCL2, CCL5, IL-6 and TNFα) was significantly increased in obese subjects at baseline as compared with normal weight controls. The baseline plasma concentration of inflammasome-related cytokines (IL-1β and IL-18) and of microbial translocation markers (LPS and sCD14) was augmented in obese subjects as compared with controls as well. Longitudinal analyses indicated that intensive lifestyle modification resulted in a normalization of parameters in subjects with a significant reduction of BMI after 18 months. Conclusions: In children and adolescents, obesity is characterized by the activation of the inflammasome and by an alteration of gut permeability. Successful lifestyle modification is effective in reducing inflammation, suggesting that inhibition of the inflammasome may be a potential therapeutic strategy in obesity.

Upgrading the nutritive value of rice straw (RS) is necessary to increase its contribution to enhancing meat and milk production. Present work verified whether novel Crabtree negative yeast inoculant could promote RS utilization, rumen fermentation, and milk quality in tropical crossbred lactating Holstein cows. The new stain of Crabtree negative yeasts ( Pichia kudriavzevii KKU20 and Candida tropicalis KKU20) was isolated from the rumen of dairy cattle. This study used 6 multiparous crossbreds between Holstein Frisian × Zebu dairy cows in their mid-lactation period. Dairy cows were randomly allocated to three ensiled RS with various yeast stains including Saccharomyces cerevisiae , P. kudriavzevii KKU20, and C. tropicalis KKU20 according to a 3 × 3 replicated Latin square design. Crabtree-negative yeast ( P. kudriavzevii and C. tropicalis ) increased the apparent digestibility of dry matter by about 6.9% when compared with Crabtree-positive yeast ( S. cerevisiae ). Bacterial populations were highest with ensiled RS by C. tropicalis KKU20. Ensiled RS with Crabtree-negative yeasts were significantly increased with total volatile fatty acids, but they did not affect volatile fatty acid profiles. Milk protein precentage was highest at 35.6 g/kg when C. tropicalis  was fed, and lowest when applied with S. cerevisiae and P. kudriavzevii KKU20 in ensiled RS at 34.5 and 34.1 g/kg, respectively. Thus, feeding ensiled RS with novel Crabtree negative yeast could improve RS digestion, rumen fermentation, and milk protein content in dairy cows.

Dysregulation of gut microbiota and intestinal barrier function has emerged as potential mechanisms underlying digestive diseases, yet targeted therapies are lacking The purpose of this investigation was to assess the efficacy of UCC118, a characterized probiotic strain, on exercise‐induced GI permeability in healthy humans. In a randomized, double‐blind, placebo‐controlled crossover study, seven healthy adults received 4 weeks of daily UCC118 or placebo supplementation. GI hyperpermeability was induced by strenuous treadmill running performed before and after each supplementation period. While running, participants ingested 5 g of lactulose, rhamnose, and sucrose. Urine was collected before, immediately after, and every hour for 5 h after exercise to assess GI permeability. Metagenomic sequencing was performed on fecal homogenates collected prior to exercise to identify changes in microbial diversity and taxon abundances. Inflammatory biomarkers were assessed from blood and fecal homogenates collected prior to and immediately following the cessation of exercise. Exercise significantly induced intestinal permeability of lactulose, rhamnose, and sucrose (P < 0.001). UCC118 significantly reduced sucrose (Δ = −0.38 ± 0.13 vs. 1.69 ± 0.79; P < 0.05) recovery, with no substantial change in lactulose (Δ = −0.07 ± 0.23 vs. 0.35 ± 0.15; P = 0.16) or rhamnose (Δ = −0.06 ± 0.22 vs. 0.48 ± 0.28; P = 0.22). Taxonomic sequencing revealed 99 differentially regulated bacteria spanning 6 taxonomic ranks (P < 0.05) after UCC118 supplementation. No differences in plasma IL‐6 or fecal zonulin were observed after UCC118 supplementation. The results described herein provide proof of principle that 4 weeks of UCC118 supplementation attenuated exercise‐induced intestinal hyperpermeability. Further research is warranted to investigate the as‐yet‐to‐be defined molecular processes of intestinal hyperpermeability and the effects of probiotic supplementation. Dysregulation of gut microbiota and intestinal barrier function have emerged as potential mechanisms underlying digestive diseases, yet targeted therapies are lacking. In a randomized, double‐blind, placebo‐controlled crossover study, 7 healthy adults 30 received 4 weeks of daily UCC118 or placebo supplementation. UCC118 significantly reduced sucrose recovery. Taxonomic sequencing revealed 99 differentially regulated gut microbes by UCC118. The results herein provide proof of principle that UCC118 supplementation can reduce intestinal hyperpermeability.

Background Absorption of EPA and DHA from Omega-3-acid ethyl ester (EE) concentrate supplements occurs most efficiently when taken in context of a fatty meal; adequate fat intake is required to release bile salts that emulsify and pancreatic enzymes that digest omega-3-containing lipids in the intestine. Current guidelines recommend reduction in fat intake and therefore there is a need to optimize the absorption of Omega-3 in those consuming low-fat or no-fat meals. To this end, BASF has developed an Absorption Acceleration Technology, a novel self-micro-emulsifying delivery system (SMEDS) formulation of highly concentrated Omega-3-acid EE which enables rapid emulsification and microdroplet formation upon entering the aqueous environment of the gut therefore enhances the absorption. Methods Two separate single dose, crossover studies were conducted to determine the relative bioavailability of omega-3-acid EE concentrate, either as a novel SMEDS formulation (PRF-021) or as control, in healthy fasted male and female adults at two dose levels (Study 1 “low dose”: 630 mg EPA + DHA in PRF-021 vs. 840 mg EPA + DHA in control; Study 2 “high dose”: 1680 mg EPA + DHA in PRF-021 vs. 3360 mg EPA + DHA in control). Blood samples were collected immediately before supplementation and at defined time intervals for 48 h. Plasma concentration of total EPA and DHA were determined for pharmacokinetic analysis, area under the curve (AUC) and maximum observed concentration (C max ) was determined. Results Total EPA plus DHA absorption from SMEDS formulation PRF-021 were 6.4 and 11.5 times higher compared to control in low- and high-dose studies respectively, determined as the ratio of baseline corrected, dose normalized AUC 0-24h of PRF-021 over that of control. EPA and DHA individually showed differing levels of enhancement: the AUC 0-24h ratio for EPA was 23.8 and 25.7 in low and high dose studies, respectively, and the AUC 0-24h ratio for DHA was 3.6 and 5.6 in low and high dose studies, respectively. C max was also increased for both EPA and DHA 2.7- to 9.2-fold. Conclusion PRF-021 is a novel SMEDS formulation of Omega-3-acid EE demonstrating a marked improvement in absorption of a single dose of EPA and DHA EE under fasted conditions. This allows adequate absorption of Omega-3 from the supplement without the requirement of a high-fat meal.

Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicory oligofructose and long-chain inulin (Synergy1; SYN1) would increase the absorption of both Ca and Mg and alter markers of bone turnover. Fifteen postmenopausal women (72·2 (sd 6·4) years) were treated with SYN1 or placebo for 6 weeks using a double-blind, placebo-controlled, cross-over design. Fractional Ca and Mg absorption were measured using dual-tracer stable isotopes before and after treatment. Bone turnover markers were measured at baseline, 3 and 6 weeks. Fractional absorption of Ca and Mg increased following SYN1 compared with placebo (P < 0·05). Bone resorption (by urinary deoxypyridinoline cross-links) was greater than baseline at 6 weeks of active treatment (P < 0·05). Bone formation (by serum osteocalcin) showed an upward trend at 3 weeks and an increase following 6 weeks of SYN1 (P < 0·05). Closer examination revealed a variation in response, with two-thirds of the subjects showing increased absorption with SYN1. Post hoc analyses demonstrated that positive responders had significantly lower lumbar spine bone mineral density than non-responders (dual X-ray absorptiometry 0·887 ± 0·102 v. 1·104 ± 0·121 g/cm2; P < 0·01), and changes in bone turnover markers occurred only in responders. These results suggest that 6 weeks of SYN1 can improve mineral absorption and impact markers of bone turnover in postmenopausal women. Further research is needed to determine why a greater response was found in women with lower initial spine bone mineral density.

Oranges are rich sources of flavonoids that are bioactive and may protect against age-related diseases. The absorption of orange flavanones may be affected by factors such as processing and subject anthropometric variables, and the bioactivity of the absorbed phytochemicals depends on how they are metabolised during absorption. In a randomised cross-over study, twenty subjects consumed a single portion of orange fruit (150 g) or juice (300 g) that contained the flavanones narirutin and hesperidin, and an additional 109 subjects across a broad age range (18–80 years) consumed the juice. Flavanone metabolites were measured in regularly collected samples of plasma and urine. After consumption of fruit or juice, flavanone conjugates, but not the aglycones, were detected in plasma and urine. The flavanone conjugates were shown to include the 7- and 4′-O-monoglucuronides of naringenin, the 7- and 3′-O-monoglucuronides of hesperetin, two hesperetin diglucuronides and a hesperetin sulfo-glucuronide, but no aglycones or rutinosides. Analysis of the plasma pharmacokinetic and urinary excretion data on a dose-adjusted basis indicated no difference in absorption or excretion of either flavanone between the fruit and juice matrices. In the extended urinary excretion dataset the individual variation was very large (range 0–59 % urinary yield). There was a small but significant (P < 0·05) decrease in the excretion of hesperetin (but not naringenin) with increasing age (P < 0·05), but the effects of sex, BMI and contraceptive pill use were shown not to be associated with the variation in flavanone excretion.

Lycopene is present mainly as cis-isomers in human serum and tissues whereas all-trans-lycopene predominates in tomato products, suggesting that all-trans-lycopene is isomerised in the body or is less bioavailable. The objectives of the present study were to develop processing conditions for tomatoes to obtain products with different cis-trans-lycopene isomer distribution and to assess their bioavailability. Healthy adult subjects (n 12) were recruited for this randomised cross-over trial. Each intervention was preceded by a 2-week washout period. Two tomato sauces, one rich in all-trans-lycopene (32·5 mg total lycopene/100 g sauce; 5 % cis-isomers), the other high in cis-lycopene (26·4 mg total lycopene/100 g sauce; 45 % cis-isomers), were produced by different heat-processing techniques. Each sauce (150 g) was served in a standardised meal at 08.00 hours after overnight fasting. Plasma TAG-rich lipoprotein fractions over 9.5 h following test-meal consumption as a measure of lycopene absorption were obtained and expressed as baseline-corrected area under the concentration v. time curves (AUC), using HPLC-electrochemical detection. AUC values adjusted for the amount lycopene consumed showed that total, total cis-, and all-trans-lycopene responses were significantly higher from the cis-isomer-rich sauce, compared with the all-trans-rich sauce, being 7·30 (sem 1·45) v. 4·74 (sem 1·08) nmol × h/l (P = 0·002), 3·80 (sem 0·76) v. 1·98 (sem 0·37) nmol × h/l (P = 0·0005) and 3·50 (sem 0·76) v. 2·76 (sem 0·76) nmol × h/l (P = 0·01), respectively. The present study demonstrates significant lycopene bioavailability from cis-lycopene-rich tomato sauce and highlights the importance of considering isomer-distribution for lycopene bioavailability. Furthermore, processing parameters can be controlled to alter isomer patterns of tomato products and influence lycopene bioavailability.