On the effect of flavonoids and dietary fibre in lingonberries on atherosclerotic plaques, lipid profiles and gut microbiota composition in Apoe-/- mice.

It has not been clarified whether the anti-atherosclerotic effect of lingonberry can be ascribed to its content of flavonoids or dietary fibre or both. The aim of this study was to evaluate the metabolic effects of whole lingonberries compared with isolated flavonoid and fibre fractions on atherosclerotic plaques, plasma lipid profiles, gut microbiota and microbiota-dependent metabolites in an Apoe-/- mouse model. Mice fed whole lingonberries showed the lowest amount of atherosclerotic plaques, while mice fed the fibre fraction had the highest formation of caecal butyric acid. Flavonoids, rather than dietary fibre, were suggested to be the components that favour proliferation of Akkermansia, as judged by the lowest abundance of this bacterium in mice fed the fibre fraction. All groups fed lingonberry diets had both, lower Firmicutes/Bacteroidetes ratios and creatinine concentrations, compared with the control. To conclude, different components in lingonberries are associated with different physiological effects in Apoe-/- mice.

Development of a real-time quantitative PCR method for detection and quantification of Prevotella copri.

BACKGROUND: Since its discovery in 2007, the importance of the human gut bacterium Prevotella copri (P. copri) has been widely recognized with its links to diet and health status and potential as next generation probiotic. Therefore, precise, convenient and cost-effective diagnostic tools for the detection and quantification of P. copri from clinical and environmental samples are needed. RESULTS: In this study, a Sybr Green qPCR protocol for P. copri detection and quantification was developed and tested on P. copri-spiked murine faeces samples targeting both the 16S rRNA gene and P. copri genome specific genes. The use of one 16S rRNA primer pair and 2 genome specific primer pairs resulted in at least 10x higher specificity and sensitivity than the primer-only PCR currently cited in the literature, reaching a sensitivity of 103 CFU/mL. Furthermore, we showed that the new 16S rRNA primer set provided the best balance of detection of a wide range of P. copri strains, while avoiding off-target detection of other Prevotella genus species. The quantification of P. copri in human stool samples using the new 16S rRNA primers also correlated well with 16S rRNA high throughput MiSeq sequencing data (r2 = 0.6604, p = 0.0074). The two genome specific primer pairs on the other hand uniquely detect the DSM18205 reference strain, allowing differential detection of indigenous and experimentally administered P. copri populations. Finally, it was shown that SYBR green qPCR mixes have an influence on sensitivity and specificity, with Biorad SsoAdvanced Universal SYBR Green Supermix performing the best under our test conditions of six commercially available SYBR green master mixes. CONCLUSIONS: This improved qPCR-based method will allow accurate P. copri identification and quantification. Moreover, this methodology can also be applied to identify other bacterial species in complex samples.

Lingonberries and their two separated fractions differently alter the gut microbiota, improve metabolic functions, reduce gut inflammatory properties, and improve brain function in ApoE-/- mice fed high-fat diet.

Lingonberries (LB) have been shown to have beneficial metabolic effects, which is associated with an altered gut microbiota. This study investigated whether the LB-induced improvements were associated with altered gut- and neuroinflammatory markers, as well as cognitive performance in ApoE-/- mice fed high-fat (HF) diets. Whole LB, as well as two separated fractions of LB were investigated. Eight-week-old male ApoE-/- mice were fed HF diets (38% kcal) containing whole LB (wLB), or the insoluble (insLB) and soluble fractions (solLB) of LB for 8 weeks. Inclusion of wLB and insLB fraction reduced weight gain, reduced fat deposition and improved glucose response. Both wLB and insLB fraction also changed the caecal microbiota composition and reduced intestinal S100B protein levels. The solLB fraction mainly induced weight loss in the mice. There were no significant changes in spatial memory, but significant increases in synaptic density in the hippocampus were observed in the brain of mice-fed wLB and insLB. Thus, this study shows that all lingonberry fractions counteracted negative effects of HF feedings on metabolic parameters. Also, wLB and insLB fraction showed to potentially improve brain function in the mice.

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe-/- Mice.

Objective- To investigate the effect of gut microbiota and diet on atherogenesis. Approach and Results- Here, we investigated the interaction between the gut microbiota and diet on atherosclerosis by feeding germ-free or conventionally raised Apoe-/- mice chow or Western diet alone or supplemented with choline (which is metabolized by the gut microbiota and host enzymes to trimethylamine N-oxide) for 12 weeks. We observed smaller aortic lesions and lower plasma cholesterol levels in conventionally raised mice compared with germ-free mice on a chow diet; these differences were not observed in mice on a Western diet. Choline supplementation increased plasma trimethylamine N-oxide levels in conventionally raised mice but not in germ-free mice. However, this treatment did not affect the size of aortic lesions or plasma cholesterol levels. Gut microbiota composition was analyzed by sequencing of 16S rRNA genes. As expected, the global community structure and relative abundance of many taxa differed between mice fed chow or a Western diet. Choline supplementation had minor effects on the community structure although the relative abundance of some taxa belonging to Clostridiales was altered. Conclusions- In conclusion, the impact of the gut microbiota on atherosclerosis is dietary dependent and is associated with plasma cholesterol levels. Furthermore, the microbiota was required for trimethylamine N-oxide production from dietary choline, but this process could not be linked to increased atherosclerosis in this model.

Monovalerin and trivalerin increase brain acetic acid, decrease liver succinic acid, and alter gut microbiota in rats fed high-fat diets.

PURPOSE: Short-chain fatty acids (SCFA) are known for their anti-inflammatory properties and may also prevent against the development of metabolic diseases. This study investigated possible effects of two valeric acid esters, monovalerin (MV) and trivalerin (TV) in rats fed high-fat diets. METHODS: Four groups of rats were given a low-fat diet (LF) or a high-fat control diet (HFC) with or without supplementation of MV or TV (5 g/kg) for 3 weeks (n = 7/group). SCFA (caecum, blood, liver and brain), succinic acid (liver), microbiota (caecum), lipid profile (liver and blood) and the inflammatory biomarker, lipopolysaccharide-binding protein (blood) were analysed at the end of the experiment. RESULTS: Supplementation of MV and TV to a high-fat diet increased 1.5-fold the amounts of acetic acid in the brain and 1.7-fold serum concentration of valeric acid, whereas liver succinic acid was reduced by 1.5-fold. Although liver triglyceride levels were higher in both MV and TV groups compared with the LF group, liver LDL/HDL ratio was lower in the MV group (P < 0.05). The caecal microbiota composition was altered, with threefold higher abundance of Bacteroidetes and higher ratio of Bacteroidetes/Firmicutes in the MV group compared with the HFC and LF groups. Acetic acid in the brain was negatively correlated with TM7, family S24-7 and rc4-4, and positively associated to Tenericutes and Anaeroplasma. CONCLUSIONS: The present study shows that MV and TV in the specified dose can affect caecal microbiota composition and, therefore, bacterial metabolites in the liver, serum and brain as well as the lipid profile in the liver.

Improvement in cardiometabolic risk markers following a multifunctional diet is associated with gut microbial taxa in healthy overweight and obese subjects.

PURPOSE: A multifunctional diet (MFD) targeting subclinical inflammation was developed as a tool to decrease risk factors for cardiometabolic disease in healthy "at-risk" individuals (BMI 25-33 kg/m2). MFD contains several components that are degraded in the colon by the microbiota, such as dietary fibers from rye, barley, oats and berries. It also contains soy beans, oily fish and plant stanols. In previous studies, we have observed improved cardiometabolic markers in healthy at-risk individuals after 4-8 week intake of MFD. However, whether these improvements can be associated with changes in the gut microbiota composition has not been investigated. In the present study, we analyzed the gut microbiota before and after an 8-week dietary intervention with MFD. METHODS: Cardiometabolic at-risk individuals (n = 47), between 51 and 72 years old and with a BMI of 25-33 kg/m2, were given either the MFD or a control diet lacking the functional ("active") components for 8 weeks in a parallel, randomized design. Next-generation sequencing of bacterial 16S rRNA genes was used to analyze the gut microbiota composition. RESULTS: The 8-week intervention with MFD did not significantly alter the gut microbiota composition at phylum or genus taxonomic levels, while LEfSE analysis identified increased abundance of Prevotella copri in the MFD group as compared to the control group. Treponema correlated positively with blood pressure. In contrast, Faecalibacterium showed a negative association with blood pressure, while Bilophila appeared to associate with a negative blood lipid profile. CONCLUSIONS: Taken together, results from the present study may be used in the further development of effective dietary concepts capable of reducing cardiometabolic risk markers in humans through a targeted modulation of the gut microbial community. TRIAL REGISTRATION NUMBER: Clinical Trials.gov NCT02148653.

Long-Term Changes to the Microbiome, Blood Lipid Profiles and IL-6 in Female and Male Swedish Patients in Response to Bariatric Roux-en-Y Gastric Bypass.

Lipid metabolism dysregulation is a critical factor contributing to obesity. To counteract obesity-associated disorders, bariatric surgery is implemented as a very effective method. However, surgery such as Roux-en-Y gastric bypass (RYGB) is irreversible, resulting in life-long changes to the digestive tract. The aim of the present study was to elucidate changes in the fecal microbiota before and after RYGB in relation to blood lipid profiles and proinflammatory IL-6. Here, we studied the long-term effects, up to six years after the RYGB procedure, on 15 patients' gut microbiomes and their post-surgery well-being, emphasizing the biological sex of the patients. The results showed improved health among the patients after surgery, which coincided with weight loss and improved lipid metabolism. Health changes were associated with decreased inflammation and significant alterations in the gut microbiome after surgery that differed between females and males. The Actinobacteriota phylum decreased in females and increased in males. Overall increases in the genera Prevotella, Paraprevotella, Gemella, Streptococcus, and Veillonella_A, and decreases in Bacteroides_H, Anaerostipes, Lachnoclostridium_B, Hydrogeniiclostridium, Lawsonibacter, Paludicola, and Rothia were observed. In conclusion, our findings indicate that there were long-term changes in the gut microbiota after RYGB, and shifts in the microbial taxa appeared to differ depending on sex, which should be investigated further in a larger cohort.

Effects of Whole Brown Bean and Its Isolated Fiber Fraction on Plasma Lipid Profile, Atherosclerosis, Gut Microbiota, and Microbiota-Dependent Metabolites in Apoe-/- Mice.

The health benefits of bean consumption are widely recognized and are largely attributed to the dietary fiber content. This study investigated and compared the effects of whole brown beans and an isolated bean dietary fiber fraction on the plasma lipid profile, atherosclerotic plaque amount, gut microbiota, and microbiota-dependent metabolites (cecal short-chain fatty acids (SCFAs) and plasma methylamines) in Apoe-/- mice fed high fat diets for 10.5 weeks. The results showed that both whole bean and the isolated fiber fraction had a tendency to lower atherosclerotic plaque amount, but not plasma lipid concentration. The whole bean diet led to a significantly higher diversity of gut microbiota compared with the high fat diet. Both bean diets resulted in a lower Firmicutes/Bacteroidetes ratio, higher relative abundance of unclassified S24-7, Prevotella, Bifidobacterium, and unclassified Clostridiales, and lower abundance of Lactobacillus. Both bean diets resulted in higher formation of all cecal SCFAs (higher proportion of propionic acid and lower proportion of acetic acid) and higher plasma trimethylamine N-oxide concentrations compared with the high fat diet. Whole beans and the isolated fiber fraction exerted similar positive effects on atherosclerotic plaque amount, gut microbiota, and cecal SCFAs in Apoe-/- mice compared with the control diets.

Identification of Nordic Berries with Beneficial Effects on Cognitive Outcomes and Gut Microbiota in High-Fat-Fed Middle-Aged C57BL/6J Mice.

High-fat diets are associated with neuronal and memory dysfunction. Berries may be useful in improving age-related memory deficits in humans, as well as in mice receiving high-fat diets. Emerging research has also demonstrated that brain health and cognitive function may be related to the dynamic changes in the gut microbiota. In this study, the impact of Nordic berries on the brain and the gut microbiota was investigated in middle-aged C57BL/6J mice. The mice were fed high-fat diets (60%E fat) supplemented with freeze-dried powder (6% dwb) of bilberry, lingonberry, cloudberry, blueberry, blackcurrant, and sea buckthorn for 4 months. The results suggest that supplementation with bilberry, blackcurrant, blueberry, lingonberry, and (to some extent) cloudberry has beneficial effects on spatial cognition, as seen by the enhanced performance following the T-maze alternation test, as well as a greater proportion of DCX-expressing cells with prolongation in hippocampus. Furthermore, the proportion of the mucosa-associated symbiotic bacteria Akkermansia muciniphila increased by 4-14 times in the cecal microbiota of mice fed diets supplemented with lingonberry, bilberry, sea buckthorn, and blueberry. These findings demonstrate the potential of Nordic berries to preserve memory and cognitive function, and to induce alterations of the gut microbiota composition.

Varying Dietary Component Ratios and Lingonberry Supplementation May Affect the Hippocampal Structure of ApoE-/- Mice.

OBJECTIVE: This study aimed to investigate and compare the morphological and biochemical characteristics of the hippocampus and the spatial memory of young adult ApoE-/- mice on a standard chow diet, a low-fat diet (LFD), a high-fat diet (HFD), and an HFD supplemented with lingonberries. METHODS: Eight-week-old ApoE-/- males were divided into five groups fed standard chow (Control), an LFD (LF), an HFD (HF), and an HFD supplemented with whole lingonberries (HF+WhLB) or the insoluble fraction of lingonberries (HF+InsLB) for 8 weeks. The hippocampal cellular structure was evaluated using light microscopy and immunohistochemistry; biochemical analysis and T-maze test were also performed. Structural synaptic plasticity was assessed using electron microscopy. RESULTS: ApoE-/- mice fed an LFD expressed a reduction in the number of intact CA1 pyramidal neurons compared with HF+InsLB animals and the 1.6-3.8-fold higher density of hyperchromic (damaged) hippocampal neurons relative to other groups. The LF group had also morphological and biochemical indications of astrogliosis. Meanwhile, both LFD- and HFD-fed mice demonstrated moderate microglial activation and a decline in synaptic density. The consumption of lingonberry supplements significantly reduced the microglia cell area, elevated the total number of synapses and multiple synapses, and increased postsynaptic density length in the hippocampus of ApoE-/- mice, as compared to an LFD and an HFD without lingonberries. CONCLUSION: Our results suggest that, in contrast to the inclusion of fats in a diet, increased starch amount (an LFD) and reduction of dietary fiber (an LFD/HFD) might be unfavorable for the hippocampal structure of young adult (16-week-old) male ApoE-/- mice. Lingonberries and their insoluble fraction seem to provide a neuroprotective effect on altered synaptic plasticity in ApoE-/- animals. Observed morphological changes in the hippocampus did not result in notable spatial memory decline.

Effects of Proteases from Pineapple and Papaya on Protein Digestive Capacity and Gut Microbiota in Healthy C57BL/6 Mice and Dose-Manner Response on Mucosal Permeability in Human Reconstructed Intestinal 3D Tissue Model.

Cysteine proteases obtained from the stem of pineapple or papaya latex, bromelain and papain, respectively, exhibit a broad spectrum of beneficial effects on human health. However, their effects on gut microbiota composition or dose-manner effects on the intestinal integrity of healthy tissue have not been evaluated. In this study, C57BL/6 young, healthy mice were fed bromelain or papain in a dose of 1 mg per animal/day for three consecutive days, followed by the assessment of digestive protein capacity, intestinal morphology and gut microbiota composition. Furthermore, a human reconstructed 3D tissue model EpiIntestinal (SMI-100) was used to study the effects of 1, 0.1 and 10 mg/mL doses of each enzyme on tissue integrity and mucosal permeability using TEER measurements and passage of Lucifer Yellow marker from the apical to the basolateral side of the mucosa. The results indicated that fruit proteases have the potential to modulate gut microbiota with decreasing abundance of Proteobacteria and increasing beneficial Akkermansia muciniphila. The enhancement of pancreatic trypsin was observed in bromelain and papain supplementation, while bromelain also increased the thickness of the ileal mucosa. Furthermore, an in vitro study showed a dose-dependent interruption in epithelial integrity, which resulted in increased paracellular permeability by the highest doses of enzymes. These findings define bromelain and papain as promising enzymatic supplementation for controlled enhancement of paracellular uptake when needed, together with beneficial effects on the gut microbiota.

Monobutyrin and monovalerin improve gut-blood-brain biomarkers and alter gut microbiota composition in high-fat fed apolipoprotein-E-knockout rats.

Monobutyrin (MB) and monovalerin (MV), glycerol esters of short-chain fatty acids (SCFAs), have been shown to positively influence lipid profile and biomarkers in the gut and brain. This study examined whether MB and MV in high-fat diets, affected microbiota composition and gut-blood-brain markers in apolipoprotein E deficient (ApoE-/-) rats, a model for studies of lipid-associated disorders, and neurodegenerative processes in Alzheimer's disease (AD). ApoE-/- rats fed MB and MV increased Tenericutes and the brain neurotransmitter γ-aminobutyric acid (GABA), while the blood stress hormone corticosterone decreased compared to control rats. Only rats that received MB showed a significant increase in cholic acid and Adlercreutzia in the caecum. In rats fed MV, the decrease of Proteobacteria was associated with decreased corticosterone levels. Conclusively, dietary supplementation of SCFA glycerol esters can modulate gut-blood-brain markers and alter gut microbiota composition in ApoE-/- rats, suggesting that SCFAs also could counteract lipid disorders-related diseases.

Evaluation of hypoglycemic effect, safety and immunomodulation of Prevotella copri in mice.

The gut bacterium Prevotella copri (P. copri) has been shown to lower blood glucose levels in mice as well as in healthy humans, and is a promising candidate for a next generation probiotic aiming at prevention or treatment of obesity and type 2 diabetes. In this study the hypoglycemic effect of live P. copri was confirmed in mice and pasteurization of P. copri was shown to further enhance its capacity to improve glucose tolerance. The safety of live and pasteurized P. copri was evaluated by a 29-day oral toxicity study in mice. P. copri did not induce any adverse effects on body growth. General examination of the mice, gross pathological and histological analysis showed no abnormalities of the vital organs. Though relative liver weights were lower in the pasteurized (4.574 g ± 0.096) and live (4.347 g ± 0.197) P. copri fed groups than in the control mice (5.005 g ± 0.103) (p = 0.0441 and p = 0.0147 respectively), no liver biochemical marker aberrations were detected. Creatinine serum levels were significantly lower in mice fed with live (p = 0.001) but not pasteurized (p = 0.163) P. copri compared to those of control mice. Haematological parameter analysis and low plasma Lipopolysaccharide Binding Protein (LBP) levels ruled out systemic infection and inflammation. Immunomodulation capacity by P. copri as determined by blood plasma cytokine analysis was limited and gut colonisation occurred in only one of the 10 mice tested. Taken together, no major adverse effects were detected in P. copri treated groups compared to controls.

Xylooligosaccharides Increase Bifidobacteria and Lachnospiraceae in Mice on a High-Fat Diet, with a Concomitant Increase in Short-Chain Fatty Acids, Especially Butyric Acid.

Effects of xylooligosaccharides (XOSs) as well as a mixture of XOS, inulin, oligofructose, and partially hydrolyzed guar gum (MIX) in mice fed a high-fat diet (HFD) were studied. Control groups were fed an HFD or a low-fat diet. Special attention was paid to the cecal composition of the gut microbiota and formation of short-chain fatty acids, but metabolic parameters were also documented. The XOS group had significantly higher cecum levels of acetic, propionic, and butyric acids than the HFD group, and the butyric acid content was higher in the XOS than in the MIX group. The cecum microbiota of the XOS group contained more Bifidobacteria, Lachnospiraceae, and S24-7 bacteria than the HFD group. A tendency of lower body weight gain was observed on comparing the XOS and HFD groups. In conclusion, the XOS was shown to be a promising prebiotic candidate. The fiber diversity in the MIX diet did not provide any advantages compared to the XOS diet.

Monobutyrin and Monovalerin Affect Brain Short-Chain Fatty Acid Profiles and Tight-Junction Protein Expression in ApoE-Knockout Rats Fed High-Fat Diets.

Monobutyrin (MB) and monovalerin (MV), esters of short-chain fatty acids (SCFAs), have previously been shown to reduce liver cholesterol and inflammation in conventional rats fed high-fat diets. This study explored the potential effects of MB and MV in hypercholesterolemic apolipoprotein E-knockout (ApoE-/-) rats. ApoE-/- rats were fed three high-fat (HF) diets, pure or supplemented with MB or MV (1%), for 5 weeks. One group of conventional rats (C) was also fed the pure high-fat diet and another group of ApoE-/- rats a low-fat (LF) diet. Blood and liver lipids, urinary lactulose/mannitol, SCFAs (blood and brain), tight junction proteins (small intestine and brain), and inflammation-related markers (blood, brain, and liver) were analyzed. MV supplementation elevated serum high-density lipoprotein (HDL) cholesterol and valeric acid concentration (p < 0.05), while the amounts of isovaleric acid in the brain were reduced (p < 0.05). MB increased butyric acid amounts in the brain, while the plasma concentration of interleukin 10 (IL-10) was lowered (p < 0.05). Both MV and MB upregulated the expression of occludin and zonula occludens-1 (ZO-1) in the brain (p < 0.05). Supplementation of MB or MV affected HDL cholesterol, the expression of tight junction proteins, and SCFA profiles. MB and MV may therefore be promising supplements to attenuate lipid metabolic disorders caused by high-fat intake and genetic deficiency.

Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson's disease patients has been linked with increased intestinal permeability-leaky gut syndrome. The intestine contains microbiota, most dominant phyla being Bacteroidetes and Firmicutes; in pathogenic or disease conditions the balance between these bacteria might be disrupted. The present study investigated whether there is evidence for an increased intestinal permeability and dysbiosis in the R6/2 mouse model of HD. Our data demonstrate that decreased body weight and body length in R6/2 mice is accompanied by a significant decrease in colon length and increased gut permeability compared to wild type littermates, without any significant changes in the protein levels of the tight junction proteins (occludin, zonula occludens). Moreover, we found an altered gut microbiota in R6/2 mice with increased relative abundance of Bacteroidetes and decreased of Firmicutes. Our results indicate an increased intestinal permeability and dysbiosis in R6/2 mice and further studies investigating the clinical relevance of these findings are warranted.

Correction: Nguyen et al. "Monobutyrin Reduces Liver Cholesterol and Improves Intestinal Barrier Function in Rats Fed High-Fat Diets" Nutrients 2019, 11, 308.

The authors wish to make a correction to the published version of their paper [...].

Monobutyrin Reduces Liver Cholesterol and Improves Intestinal Barrier Function in Rats Fed High-Fat Diets.

Butyric acid has been shown to reduce high-fat diet-related metabolic disturbances and to improve intestinal barrier function due to its potent anti-inflammatory capacity. This study investigates whether a butyric acid ester, monobutyrin (MB) affects lipid profiles and gut barrier function in a dose-response manner in rats fed butter- or lard-based high-fat diets. Four-week-old male Wistar rats were fed butter-based diets containing 0, 0.25, 0.75 and 1.5 MB g/100 g (dry weight basis) or 0.5 glycerol g/100 g, and diets with lard (La) containing 0 and 0.5 MB g/100 g or a low-fat control diet for 3⁻4 weeks. Lipid profiles in blood and liver tissue, intestinal permeability and cecal short-chain fatty acids were examined. The results showed a dose-dependent decrease in liver total cholesterol for 1.5 MB (p < 0.05) and liver triglycerides for 0.75 MB (p < 0.05) and 1.5 MB (p = 0.08) groups compared to the high-fat control group. Furthermore, a lower excretion of mannitol in urine in the 1.5 MB group indicated improved intestinal barrier function. When MB was supplemented in the lard-based diet, serum total cholesterol levels decreased, and total amount of liver high-density lipoprotein-cholesterol increased. Thus, MB dietary supplementation can be effective in counteracting lipid metabolism disturbances and impaired gut barrier function induced by high-fat diets.

Determination of free and conjugated bile acids in serum of Apoe(-/-) mice fed different lingonberry fractions by UHPLC-MS.

Bile acids (BAs) are known to be involved in cholesterol metabolism but interactions between the diet, BA profiles, gut microbiota and lipid metabolism have not been extensively explored. In the present study, primary and secondary BAs including their glycine and taurine-conjugated forms were quantified in serum of Apoe-/- mice by protein precipitation followed by reversed phase ultra-high-performance liquid chromatography and QTOF mass spectrometry. The mice were fed different lingonberry fractions (whole, insoluble and soluble) in a high-fat setting or cellulose in a high and low-fat setting. Serum concentrations of BAs in mice fed cellulose were higher with the high-fat diet compared to the low-fat diet (20-70%). Among the lingonberry diets, the diet containing whole lingonberries had the highest concentration of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), tauro-ursodeoxycholic acid (T-UDCA), α and ω-muricholic acids (MCA) and tauro-α-MCA (T-α-MCA), and the lowest concentration of tauro-cholic acid (T-CA), deoxycholic acid (DCA) and tauro-deoxycholic acid (T-DCA). The glycine-conjugated BAs were very similar with all diets. CDCA, UDCA and α-MCA correlated positively with Bifidobacterium and Prevotella, and T-UDCA, T-α-MCA and ω-MCA with Bacteroides and Parabacteroides.

Postprandial Responses of Serum Bile Acids in Healthy Humans after Ingestion of Turmeric before Medium/High-Fat Breakfasts.

SCOPE: Bile acids (BAs) are known to regulate a number of metabolic activities in the body. However, very little is known about how BAs are affected by diet. This study aims to investigate whether a single dose of turmeric-based beverage (TUR) before ingestion of medium- (MF) or high-fat (HF) breakfasts would improve the BA profile in healthy subjects. METHODS AND RESULTS: Twelve healthy subjects are assigned to a randomized crossover single-blind study. The subjects receive isocaloric MF or HF breakfasts after a drink containing flavored water with or without an extract of turmeric with at least 1-week wash-out period between the treatments. Postprandial BAs are measured using protein precipitation followed by ultra-high-performance liquid chromatography-mass spectrometry analysis. The concentration of BAs is generally higher after HF than MF breakfasts. Ingestion of TUR before MF breakfast increases the serum concentrations of free and conjugated forms of cholic (CA) and ursodeoxycholic acids (UDCA), as well as the concentrations of chenodeoxycholic acid (CDCA) and its taurine-conjugated forms. However, the concentration of conjugated forms of deoxycholic acid (DCA) decreases when TUR is taken before HF breakfast. CONCLUSION: TUR ingestion before MF and HF breakfasts improve BA profiles and may therefore have potential health-promoting effects on BA metabolism.