Effects of dietary supplementation of fish oil plus vitamin D3 on gut microbiota and fecal metabolites, and their correlation with nonalcoholic fatty liver disease risk factors: a randomized controlled trial.

We previously reported that fish oil plus vitamin D3 (FO + D) could ameliorate nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether the beneficial effects of FO + D on NAFLD are associated with gut microbiota and fecal metabolites. In this study, we investigated the effects of dietary supplementation of FO + D on gut microbiota and fecal metabolites and their correlation with NAFLD risk factors. Methods: A total of 61 subjects were randomly divided into three groups: FO + D group (2.34 g day-1 of eicosatetraenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3), FO group (2.34 g day-1 of EPA + DHA), and corn oil (CO) group (1.70 g d-1 linoleic acid). Blood and fecal samples were collected at the baseline and day 90. Gut microbiota were analyzed through 16S rRNA PCR analysis, and fecal co-metabolites were determined via untargeted ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results: The relative abundance of Eubacterium (p = 0.03) and Lactobacillus (p = 0.05) increased, whereas that of Streptococcus (p = 0.02) and Dialister (p = 0.04) decreased in the FO + D group compared with the CO group. Besides, changes in tetracosahexaenoic acid (THA, C24:6 n-3) (p = 0.03) levels were significantly enhanced, whereas 8,9-DiHETrE levels (p < 0.05) were reduced in the FO + D group compared with the CO group. The changes in 1,25-dihydroxyvitamin D3 levels in the fecal samples were inversely associated with insulin resistance, which was determined using the homeostatic model assessment model (HOMA-IR, r = -0.29, p = 0.02), and changes in 8,9-DiHETrE levels were positively associated with adiponectin levels (r = -0.43, p < 0.05). Conclusion: The present results indicate that the beneficial effects of FO + D on NAFLD may be partially attributed to the impact on gut microbiota and fecal metabolites.

Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.

Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation. Intervention: A: polydextrose; B: psyllium husk; C: wheat bran + psyllium husk; D: Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001; Placebo: maltodextrin. Oligosaccharides were also included in group A to D. 16S rRNA sequencing was used to assess the gut microbiota at weeks 0, 2, and 4. A total of 242 participants completed the study. No time-by-group effect was observed for bowel movement frequency (BMF), Bristol stool scale score (BSS), and degree of defecation straining (DDS), while BSS showed mean increases of 0.95-1.05 in group A to D (all P < 0.05), but not significantly changed in placebo (P = 0.170), and 4-week change of BSS showed similarly superior effects of the interventions as compared placebo. Group D showed a marginal reduction in plasma 5-hydroxytryptamine. Group A resulted in a higher Bifidobacterium abundance than placebo at week 2 and 4. Fourteen genera showed intervention-specific increasing or decreasing trends continuously, among which Anaerostipes showed increasing trends in groups B and C, associated with BMF increase. Random forest models identified specific baseline microbial genera panels predicting intervention responders. In conclusion, we found that the dietary fibers or probiotics may relieve hard stool, with intervention-specific changes in gut microbiota relevant to constipation relief. Baseline gut microbiota may predispose the intervention responsiveness. ClincialTrials.gov number, NCT04667884.

What is the context?Supplementation of dietary fibers, such as psyllium husk or wheat bran (10 ~ 15 g/day) may relieve constipation symptoms, but bloating and flatulence are major concerns on a high fiber intake.Functional constipation patients had alternated gut microbiota profiles, while meta-analysis suggested that multispecies probiotics may increase bowel movement frequency and relieve hard stool in functional constipation.Dietary fibers or probiotics may lead to before-after changes of gut microbiota in patients with functional constipation, but time-series continued changes of gut microbiota during the intervention are unknown.Elevation of 5-hydroxytryptamine synthesis in enterochromaffin cells may affect bowel movement. And the elevated plasma 5-hydroxytryptamine was observed in functional constipation patients.What is new? Daily supplement of three prebiotic formulas with dietary fibers (polydextrose, psyllium husk, wheat bran, together with oligosaccharides), or a probiotic formula with Bifidobacterium animalis subsp. lactis HN019 + Lacticaseibacillus rhamnosus HN001 effectively relieved hard stool in functional constipation patients after 4 weeks intervention.We identified continued increasing or decreasing gut microbial genera over the intervention. Dietary fiber ­ gut microbiota (Anaerostipes)­constipation relieve (bowel movement frequency) evidence axis was identified in this human trial.Probiotic supplementation marginally reduced plasma 5-hydroxytryptamine, possibly associated with changes in BMF-related gut microbial genera.Intervention-specific baseline gut microbiota well predicted the responsiveness of constipation symptom relief.What is the impact? We provided references for the dosage and duration of dietary fiber/probiotics recommendations for adults with functional constipation, and advanced the microbial genera evidences of the fibers/probiotics-microbiota-laxation theory in humans.

Arabinoxylan from rice bran protects mice against high-fat diet-induced obesity and metabolic inflammation by modulating gut microbiota and short-chain fatty acids.

Rice bran is an important by-product of the milling industry. Arabinoxylan extracted from rice bran (RAX) is available in large quantities and is structurally different from other arabinoxylans from cereals. The anti-obesity effects of RAX and the role of microbiota have not been studied. In this work, we investigated the beneficial effects of RAX in C57BL/6J mice fed a high-fat diet (HFD). We found that supplementation of RAX significantly ameliorated HFD-induced obesity. RAX decreased HFD induced lipid accumulation and regulated genes related to hepatic fatty acid metabolism. Regulated lipid metabolism is associated with reduced systemic inflammation as indicated by TNF-α and IL-6. RAX normalized the gut microbiota and its major metabolites short-chain fatty acids (SCFAs). RAX restored the alpha diversity of the gut microbiota and increased the relative abundance of anti-inflammatory bacteria including Bifidobacterium and Akkermansia. RAX decreased pro-inflammatory bacteria including Anaerotruncus, Helicobacter, Coprococcus, and Desulfovibrio. Our results suggest that systemic inflammation bridges to the gut microbiota through LPS and SCFAs. RAX modulates the gut microbiota and SCFA production in the large intestine, thereby reducing systemic inflammation and ameliorating obesity. In brief, RAX prevented obesity through a mechanism related to the modulation of the microbiota and its metabolites.

Dietary n-3 polyunsaturated fatty acid intakes modify the effect of genetic variation in fatty acid desaturase 1 on coronary artery disease.

BACKGROUND: Previous studies suggested that dietary fatty acids could affect blood lipids by interacting with genetic variations in fatty acid desaturase 1 (FADS1). However, little is known about their direct effects on coronary artery disease (CAD). The aim of this study was to evaluate whether dietary n-3 long-chain polyunsaturated fatty acids (LCPUFAs)-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) could modulate the effect of FADS1 rs174547 polymorphism on CAD. METHODS: FADS1 single-nucleotide polymorphisms rs174547 genotypes were measured in 440 CAD patients and 838 healthy controls. Dietary EPA and DHA intakes were assessed with a validated quantitative frequency food questionnaire. The association between FADS1 rs174547 and CAD was estimated using logistic regression under both dominant and additive genetic models. The interactions between rs174547 polymorphism and LCPUFAs were analyzed by using multiple logistic regression and the "genotype × n-3 LCPUFAs" interaction term was included into the model. RESULTS: We found that the minor T allele of FADS1 rs174547 increased CAD risk (OR = 1.36, 95%CIs 1.03-1.80), and observed significant interaction between rs174547 and dietary EPA intakes on CAD (P-interaction = 0.028). The T-allele was only associated with higher CAD risk among individuals with lower dietary EPA intakes, but not in those with higher EPA intakes. Similarly, significant interaction was also observed between rs174547 and dietary DHA intakes on CAD (P-interaction = 0.020). CONCLUSIONS: Dietary n-3 LCPUFA intakes could modulate the association between FADS1 rs174547 polymorphism and CAD. High dietary n-3 LCPUFA intakes could negate the unfavorable effect of genetic variation in FADS1 on CAD in middle-aged and elderly Chinese population.

Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals.

BACKGROUND: Anthocyanins have been shown to improve endothelial function in animal models. However, whether these compounds have similar beneficial effects in humans is largely unknown. METHODS: In a short-term crossover study, 12 hypercholesterolemic individuals were given oral anthocyanins (320 mg) isolated from berries or placebo. Brachial artery flow-mediated dilation (FMD) was assessed before and after the intervention. In a long-term intervention trial (12 weeks), 150 hypercholesterolemic individuals were given anthocyanins (320 mg/day, n = 75) or placebo (n = 75), after which we measured FMD, plasma cGMP, and other serum biomarkers. Another short-term intervention was conducted in the presence of NO-cGMP inhibitors in 6 people and in a rat aortic ring model (n = 8). RESULTS: Significant increases of FMD from 8.3% (0.6%) at baseline to 11.0% (0.8%) at 1 h and 10.1% (0.9%) at 2 h were observed after short-term anthocyanin consumption, concomitantly with increases of plasma anthocyanin concentrations (P < 0.05). In the study participants who received long-term anthocyanin intervention, compared with the control group, we observed significant increases in the FMD (28.4% vs 2.2%), cGMP (12.6% vs -1.2%), and HDL-cholesterol concentrations, but decreases in the serum soluble vascular adhesion molecule-1 and LDL cholesterol concentrations (P < 0.05). The changes in the cGMP and HDL cholesterol concentrations positively correlated with FMD in the anthocyanin group (P < 0.05). In the presence of NO-cGMP inhibitors, the effects of anthocyanin on endothelial function were abolished in human participants and in a rat aortic ring model. CONCLUSIONS: Anthocyanin supplementation improves endothelium-dependent vasodilation in hypercholesterolemic individuals. This effect involves activation of the NO-cGMP signaling pathway, improvements in the serum lipid profile, and decreased inflammation.