Background: Obesity is associated with aggressive prostate cancer, but the links between metabolic dysregulation, inflammation, adipocyte-associated signaling, and tumor growth remain incompletely defined. This study examined whether high-fat diet (HFD)-associated systemic changes and adipocyte-derived paracrine interactions are linked to prostate cancer growth in preclinical models. Methods: An HFD xenograft model and adipocyte co-culture systems were used to evaluate systemic and local tumor-supportive features. Pharmacologic/nutritional modulation was tested using green tea or EGCG, arctigenin, and the CCR2 antagonist RS 504393, alone or in combination. Tumor growth, cell proliferation, angiogenesis-related features, circulating metabolic and cytokine levels, and selected tumor-associated signaling proteins were analyzed. Results: HFD feeding was associated with increased circulating free fatty acids, IGF-1, MCP-1, IL-6, and VEGF, together with increased tumor growth, Ki67 staining, and CD31-positive microvessel density. Adipocyte co-culture systems were used to evaluate treatment-associated changes in prostate cancer cell proliferation under adipocyte-associated conditions. Combined modulation with green tea/EGCG, arctigenin, and RS 504393 was associated with greater reductions in adipocyte-associated proliferation, tumor growth, Ki67 staining, and CD31-positive microvessel density than single or dual interventions. Antibody array analysis showed treatment-associated changes in selected stress- and apoptosis-related proteins, including cleaved caspase-7 and phosphorylated Chk1. Conclusions: HFD-associated metabolic and inflammatory alterations, adipocyte-associated interactions, proliferative activity, angiogenesis-related features, and stress/apoptosis-related signaling changes were linked within a tumor-supportive framework in preclinical prostate cancer models. Combined pharmacologic/nutritional modulation was associated with reduced tumor-supportive features under HFD conditions. Further mechanistic and translational validation is needed.

The authors would like to replace Figure 3B of the following published paper [...]

Kiwifruit is renowned for its benefits to laxation. Livaux (R) is a gold kiwifruit powder retaining whole fruit benefits, including high-methoxy pectin content. Livaux was previously shown to provide laxation support and increased faecal F. prausnitzii. F. prausnitzii is known to use high-methoxy pectin as substrate. We aimed to determine the changes to laxation and faecal F. prausnitzii numbers from 600 mg of Livaux. We used a randomized, double-blinded, placebo-controlled parallel-arm study with 85 participants conducted across four North American sites, comparing 28 days of 600 mg Livaux consumption vs cellulose placebo. The study was powered for the primary outcome Complete Spontaneous Bowel Movements (CSBM). Participants visited at screening, baseline and endpoint. Anthropometric measures, hematology, clinical chemistry and hematology and fecal samples for microbiome assessment were collected at baseline and endpoint. Clinical outcomes (CSBM, Bristol Stool Form Score (BSFS), spontaneous bowel movements (SBM) and participant-assessed constipation symptoms and quality of life), food diaries and adverse events were recorded daily throughout the study. Analysis of the intent-to-treat population assessed differences from baseline to endpoint using ANOVA with post-hoc Tukey's T-test, an assessment of change from baseline to days 7, 14, 21 and 28 using repeated measures ANCOVA. Livaux supplemented participants showed significantly increased fecal F. prausnitzii relative abundance, whilst placebo did not. Participants also showed significantly improved CSBM, SBM, BSFS and constipation symptom and quality of life scores over baseline. Livaux supplementation improved laxation and increased F. prausnitzii at the low dose of 600 mg. This study was registered at https://clinicaltrials.gov/study/NCT03462199.

Constipation is a global issue which impacts quality of life. Kiwifruit promote laxation without the urgency induced by therapeutic laxatives. Actazin (R) is a skinless, seedless, cold-processed green kiwifruit powder previously shown to improve laxation at 2400 mg daily dosages. Here we investigated the laxation support provided by a 600 mg daily dosage of Actazin. A randomized, double-blinded, placebo-controlled parallel study for 28 days across four North American sites (NCT03462199) enrolled 85 participants with non-pathological constipation who had <= 3 complete spontaneous bowel movements (CSBM) per week. Participants consuming Actazin reported improved Bristol stool form scores (BSFS) over placebo (p < 0.05), improving the normality of stool form. Both Actazin and placebo showed improvements of >1 CSBM per week over baseline (p < 0.05). Actazin was safe and well tolerated by participants and resulted in changes (p < 0.05) in the relative abundance of fecal bacterial taxa consistent with consumption of kiwifruit cell wall components. This study demonstrated that once daily supplementation of 600 mg Actazin green kiwifruit powder resulted in clinically significant improvements in stool form and improved participant bowel habits in healthy individuals with occasional constipation. To the best of our knowledge this is the first recorded observation of this BSFS improvement over placebo by a kiwifruit product.

The low bioavailability of most phytochemicals limits their anticancer effects in humans. The present study was designed to test whether combining arctigenin (Arc), a lignan mainly from the seed of Arctium lappa, with green tea (GT) and quercetin (Q) enhances the chemopreventive effect on prostate cancer. We performed in vitro proliferation studies on different cell lines. We observed a strong synergistic anti-proliferative effect of GT+Q+Arc in exposing androgen-sensitive human prostate cancer LNCaP cells. The pre-malignant WPE1-NA22 cell line was more sensitive to this combination. No cytotoxicity was observed in normal prostate epithelial PrEC cells. For an in vivo study, 3-week-old, prostate-specific PTEN (phosphatase and tensin homolog) knockout mice were treated with GT+Q, Arc, GT+Q+Arc, or the control daily until 16 weeks of age. In vivo imaging using prostate-specific membrane antigen (PSMA) probes demonstrated that the prostate tumorigenesis was significantly inhibited by 40% (GT+Q), 60% (Arc at 30 mg/kg bw), and 90% (GT+Q+Arc) compared to the control. A pathological examination showed that all control mice developed invasive prostate adenocarcinoma. In contrast, the primary lesion in the GT+Q and Arc alone groups was high-grade prostatic intraepithelial neoplasia (PIN), with low-grade PIN in the GT+Q+Arc group. The combined effect of GT+Q+Arc was associated with an increased inhibition of the androgen receptor, the PI3K/Akt pathway, Ki67 expression, and angiogenesis. This study demonstrates that combining Arc with GT and Q was highly effective in prostate cancer chemoprevention. These results warrant clinical trials to confirm the efficacy of this combination in humans.

Background: Previous clinical studies showing that cinnamon spice lowers blood glucose concentrations had inconsistent results. Objectives: To determine the effect of daily cinnamon spice supplementation in an amount commonly used for seasoning on glucose concentrations in adults with obesity and prediabetes. Methods: Following a 2-wk run -in period of maintaining a low polyphenol/fiber diet, 18 participants with obesity and prediabetes underwent a 10-wk randomized, controlled, double-blind, crossover trial (mean age 51.1 y; mean fasting plasma glucose 102.9 mg/dL). The participants were randomly assigned to take cinnamon (4 g/d) or placebo for 4-wk, followed by a 2-wk washout period, and then crossed over to the other intervention for an additional 4-wk. Glucose changes were measured with continuous glucose monitoring. Oral glucose tolerance testing immediately following ingestion of cinnamon or placebo was performed at 4-time points to assess their acute effects both at the baseline and end of each intervention phase. Digestive symptom logs were obtained daily. Results: There were 694 follow-up days with 66,624 glucose observations. When compared with placebo, 24-h glucose concentrations were significantly lower when cinnamon was administered [mixed-models; effect size (ES) = 0.96; 95 % confidence interval (CI): -2.9, -1.5; P < 0.001]. Similarly, the mean net-area-under-the-curve (netAUC) for glucose was significantly lower than for placebo when cinnamon was given (over 24 h; ES = -0.66; 95 % CI: 2501.7, 5412.1, P = 0.01). Cinnamon supplementation resulted in lower glucose peaks compared with placebo (Delta peak 9.56 + 9.1 mg/dL compared with 11.73 + 8.0 mg/dL; ES = -0.57; 95 % CI: 0.8, 3.7, P = 0.027). Glucose-dependent-insulinotropic-polypeptide concentrations increased during oral glucose tolerance testing + cinnamon testing (mixed-models; ES = 0.51; 95 % CI: 1.56, 100.1, P = 0.04), whereas triglyceride concentrations decreased (mixed-models; ES = 0.55; 95 % CI: -16.0, -1.6, P = 0.02). Treatment adherence was excellent in both groups (cinnamon: 97.6 + 3.4 % compared with placebo: 97.9 + 3.7 %; ES = -0.15; 95 % CI: -1.8, 0.2, P = 0.5). No differences were found in digestive symptoms (abdominal pain, borborygmi, bloating, excess flatus, and stools/day) between cinnamon and placebo groups. Conclusions: Cinnamon, a widely available and low-cost supplement, may contribute to better glucose control when added to the diet in people who have obesity-related prediabetes.

PURPOSE Men on active surveillance (AS) for prostate cancer are extremely interested in dietary changes or supplements to prevent progression of their disease. We sought to determine whether a high omega-3, low omega-6 fatty acid diet with fish oil capsules (D + FO) decreases proliferation (Ki-67) in prostate biopsies in men with prostate cancer on AS over a 1-year time period. METHODS In this phase II, prospective randomized trial, men (N = 100) with grade group 1 or 2 prostate cancer who elected AS were randomly assigned to the D + FO or a control group. Same-site prostate biopsies were obtained at baseline and 1 year. The primary end point was the change in Ki-67 index from baseline to 1 year from same-site biopsies compared between the groups. RESULTS The Ki-67 index decreased in the D + FO group by approximately 15% from baseline to 1 year (1.34% at baseline, 1.14% at 1 year) and increased in the control group by approximately 24% from baseline to 1 year (1.23% at baseline, 1.52% at 1 year), resulting in a statistically significant difference in the change of Ki-67 index between the groups (95% CI, 2% to 52%, P = .043). There was no significant difference in the secondary outcomes grade group, tumor length, Decipher genomic score, or prostate-specific antigen between the two groups. Four patients in the D + FO group were withdrawn from the trial because of adverse events related to the FO. CONCLUSION A high omega-3, low omega-6 diet with FO for 1 year resulted in a significant reduction in Ki-67 index, a biomarker for prostate cancer progression, metastasis, and death. These findings support future phase III trials incorporating this intervention in men on AS.

Supplementary Table S1 from Effect of Altering Dietary ω-6/ω-3 Fatty Acid Ratios on Prostate Cancer Membrane Composition, Cyclooxygenase-2, and Prostaglandin E2

SCOPE:Four weeks' of concentrated grape powder (GP) consumption reduces circulating cholesterol in healthy free-living subjects consuming a low-fiber/low-polyphenol diet. Here, the study aims to investigate the underlying mechanisms for cholesterol reduction by evaluating biomarkers of cholesterol de novo biosynthesis, intestinal absorption, miRNA involved in transcriptional regulation of cholesterol metabolism, as well as cholesterol oxidation. METHODS AND RESULTS:Fasting plasma samples collected from 19 healthy free-living subjects at baseline and week 4 of GP consumption are used in this study. Gas chromatography-mass (GC-MS) analysis of plasma samples shows that lathosterol, a precursor of cholesterol synthesis, is significantly decreased after GP consumption indicating reduced cholesterol de novo biosynthesis. Markers of intestinal absorption, campesterol, and β-sitosterol are not changed. Realtime PCR shows that plasma exosomal miRNA-1 is increased after GP consumption. GC-MS also shows that GP consumption reduces the plasma cholesterol oxidation product 27-hydroxycholesterol (27-HC). CONCLUSIONS:This study enhances the understanding of the mechanisms of the cholesterol lowering effects of GP, and provides new insights into the potential health benefits of grape consumption.

We recently demonstrated that the consumption of mixed tree nuts (MTNs) during caloric restriction decreased cardiovascular risk factors and increased satiety. Tryptophan (Trp) metabolism has been indicated as a factor in cardiovascular disease. Here, we investigated the effect of MTNs on Trp metabolism and the link to cardiovascular risk markers. Plasma and stool were collected from 95 overweight individuals who consumed either MTNs (or pretzels) daily as part of a hypocaloric weight loss diet for 12 weeks followed by an isocaloric weight maintenance program for an additional 12 weeks. Plasma and fecal samples were evaluated for Trp metabolites by LC–MS and for gut microbiota by 16S rRNA sequencing. Trp–kynurenine metabolism was reduced only in the MTNs group during weight loss (baseline vs. week 12). Changes in Trp–serotonin (week 24) and Trp–indole (week 12) metabolism from baseline were increased in the MTNs group compared to the pretzel group. Intergroup analysis between MTN and pretzel groups does not identify significant microbial changes as indicated by alpha diversity and beta diversity. Changes in the relative abundance of genus Paludicola during intervention are statistically different between the MTNs and pretzel group with p < 0.001 (q = 0.07). Our findings suggest that consumption of MTNs affects Trp host and microbial metabolism in overweight and obese subjects.

Background Preclinical and clinical translational research supports the role of an ω-3 fatty acid diet for prostate cancer prevention and treatment. The anti-prostate cancer effects of an ω-3 diet require a functional host g-protein coupled receptor 120 (GPR120) but the underlying effects on the tumor microenvironment and host immune system are yet to be elucidated. Methods Friend leukemia virus B (FVB) mice received bone marrow from green fluorescent protein (GFP) labeled GPR120 wild-type (WT) or knockout (KO) mice followed by implanting Myc-driven mouse prostate cancer (MycCap) allografts and feeding an ω-3 or ω-6 diet. Tumor associated immune cells were characterized by flow cytometry, and CD206+ tumor infiltrating M2-like macrophages were isolated for gene expression studies. MycCap prostate cancer cell conditioned medium (CM) was used to stimulate murine macrophage cells (RAW264.7) and bone marrow-derived (BMD) macrophages to study the effects of docosahexanoic acid (DHA, fish-derived ω-3 fatty acid) on M2 macrophage function and cholesterol metabolism. Results The bone marrow transplantation study showed that an ω-3 as compared to an ω-6 diet inhibited MycCaP allograft tumor growth only in mice receiving GPR120 WT but not GPR120 KO bone marrow. In the ω-3 group, GPR120 WT BMD M2-like macrophages infiltrating the tumor were significantly reduced in number and gene expression of cholesterol transporters Abca1, Abca6, and Abcg1. RAW264.7 murine macrophages and BMDMs exposed to MycCaP cell CM had increased gene expression of cholesterol transporters, depleted cholesterol levels, and were converted to the M2 phenotype. These effects were inhibited by DHA through the GPR120 receptor. Conclusion Host bone marrow cells with functional GPR120 are essential for the anticancer effects of dietary ω-3 fatty acids, and a key target of the ω-3 diet are the M2-like CD206+ macrophages. Our preclinical findings provide rationale for clinical trials evaluating ω-3 fatty acids as a potential therapy for prostate cancer through inhibition of GPR120 functional M2-like macrophages.

Background The antiprostate cancer effects of dietary ω-3 fatty acids (FAs) were previously found to be dependent on host G-protein coupled receptor 120 (GPR120). Using an orthotopic tumor model and an ex-vivo model of bone marrow derived M2-like macrophages, we sought to determine if ω-3 FAs inhibit angiogenesis and activate T-cells, and if these effects are dependent on GPR120. Methods Gausia luciferase labeled MycCaP prostate cancer cells (MycCaP-Gluc) were injected into the anterior prostate lobe of FVB mice. After established tumors were confirmed by blood luminescence, mice were fed an ω-3 or ω-6 diet. Five weeks after tumor injection, tumor weight, immune cell infiltration and markers of angiogenesis were determined. An ex-vivo co-culture model of bone marrow derived M2-like macrophages from wild-type or GPR120 knockout mice with MycCap prostate cancer cells was used to determine if docosahexanoic acid (DHA, ω-3 FA) inhibition of angiogenesis and T-cell activation is dependent on macrophage GPR120. Results Feeding an ω-3 diet significantly reduced orthotopic MycCaP-Gluc tumor growth relative to an ω-6 diet. Tumors from the ω-3 group had decreased M2-like macrophage infiltration and decreased expression of angiogenesis factors. DHA significantly inhibited M2 macrophage-induced endothelial tube formation and reversed M2 macrophage-induced T-cell suppression, and these DHA effects were mediated, in part, by M2 macrophage GPR120. Conclusion Omega-3 FAs delayed orthotopic tumor growth, inhibited M2-like macrophage tumor infiltration, and inhibited M2-like macrophage-induced angiogenesis and T-cell suppression. Given the central role of M2-like macrophages in prostate cancer progression, GPR120-dependent ω-3 FA inhibition of M2-like macrophages may play an important role in prostate cancer therapeutics.

Background Avocados are a rich dietary source of monounsaturated fatty acids, carotenoids, and phenolic compounds. Clinical studies have demonstrated that oral consumption of carotenoids improved skin aging. However, no studies have investigated whether oral intake of avocado will reduce skin aging. Objectives We therefore performed this pilot study to assess whether oral consumption of one avocado daily for 8 weeks can reduce skin aging in healthy overweight women assessing skin physical characteristics and resistance to UVB radiation. Methods Thirty-nine female participants (age 27-73 years) with Fitzpatrick skin type II-IV were randomly assigned to consume either one avocado daily or continue habitual diet for 8 weeks. Facial skin elasticity, firmness, pigmentation, sebum, and hydration were determined using a cutometer on the forehead and under eye. Minimal erythema dose (MED) was determined by standardized protocol at inner arm. Results Elasticity and firmness were increased at forehead comparing 8 weeks to baseline in the avocado group. Comparing avocado to control, change in firmness marker from baseline to week 8 indicated a significant increase in forehead skin firmness in the avocado group. We did not observe any change in hydration, pigmentation, sebum, and UVB resistance between the avocado and control group, although changes in melanin and erythema were observed in both groups over time. Conclusions Our findings suggest that daily oral avocado consumption may lead to enhanced elasticity and firmness of the facial skin in healthy women. Further studies of other skin locations are required to establish the connection between avocado consumption and skin aging.

SCOPE:The study tests the hypothesis that dietary pomegranate extract (PomX) supplementation attenuates colitis in a Western diet feed IL-10 deficient (IL-10-/-) murine model. METHODS AND RESULTS:Four-week-old male IL-10-/- mice are randomly assigned to a high fat high sucrose (HFHS) diet or a HFHS diet supplement with 0.25% PomX for 8 weeks. PomX supplementation lead to significantly lower histological score for colitis (2.6 ± 0.5 vs 3.9 ± 1.0), lower spleen weight (0.11 ± 0.01 vs 0.15 ± 0.02), and lower circulating Interleukin 6(IL-6) levels (15.8±2.2 vs 29.5±5.5) compared with HFHS fed controls. RNAseq analysis of colonic tissues showed 483 downregulated and 263 upregulated genes with PomX supplementation, which are mainly associated with inflammatory responses, defenses, and neutrophil degranulation. In addition, PomX treatment affects the cecal microbiome with increased alpha diversity, altered microbial composition, and increased levels of the tryptophan-related microbial metabolite indole propionate. CONCLUSION:The data demonstrate that dietary PomX supplementation ameliorated colitis and lowered inflammatory markers in HFHS fed IL-10-/- mice. These data support the anti-inflammatory effects of dietary PomX supplementation for IBD and a potential mediating role of gut microbiome, suggesting the need for future clinical studies to explore the use of PomX dietary supplementation in IBD patients.

Pomegranate juice (PomJ) contains ellagitannins (ETs) that are metabolized to ellagic acid (EA). Intestinal bacteria convert EA further to urolithins that are absorbed into the circulation and may provide health benefits. PomJ consumption by pregnant women was reported to be neuroprotective for their infants. In order to determine whether EA and metabolites are transferred from breast milk of mothers consuming PomJ to nursing infants, we performed an interventional pilot study and enrolled ten healthy women with full-term, exclusively breast-fed infants, consuming 8 oz. of PomJ daily for two weeks. Breast milk, plasma, urine and stool samples were collected from the mothers and the urine and stool samples from the infants before and after two weeks of PomJ consumption. Samples were analyzed using liquid chromatography-mass spectrometry to identify EA metabolites and 16S rRNA sequencing to determine changes in the microbiota. EA metabolite conjugates (dimethyl EA-glucuronide DMEAG and urolithin A-glucuronide UAG) were found in breast milk, plasma and urine from mothers and in urine of infants after 14 days of PomJ consumption. In addition, urolithin B-glucuronide (UBG) was found in breast milk, plasma and urine from two participants and urine from their infants. PomJ consumption was associated with a significant decrease in breast milk of Lactococcus, Subdoligranulum, and Acinetobacter, while the abundance of Firmicutes/Faecalibacterium increased significantly. In breast milk Escherichia/Shigella was inversely correlated to breast milk UAG. In infant stools, the abundance of Lachnoclostridium and Staphylococcus was increased. Infant stool Blautia was positively correlated to breast milk and mother plasma UBG. This pilot study demonstrates that EA and its metabolites are absorbed by the nursing infant from breast milk, excreted in urine and impact the infant gut microbiome. The concentration of EA metabolites in breast milk increased over time. Phenolic compounds in breast milk could be a way to promote neuroprotective, antioxidant and anti-inflammatory health benefits in infants.

IntroductionDevelopmental and epileptic encephalopathies (DEE) is a group of epilepsies where the epileptic activity, seizures and the underlying neurobiology contributes to cognitive and behavioral impairments. Uncovering the causes of DEE is important in order to develop guidelines for treatment and follow-up. The aim of the present study was to describe the clinical picture and to identify genetic causes in a patient cohort with DEE without known etiology, from a Norwegian regional hospital.MethodsSystematic searches of medical records were performed at Drammen Hospital, Vestre Viken Health Trust, to identify patients with epilepsy in the period 1999–2018. Medical records were reviewed to identify patients with DEE of unknown cause. In 2018, patients were also recruited consecutively from treating physicians. All patients underwent thorough clinical evaluation and updated genetic diagnostic analyses.ResultsFifty-five of 2,225 patients with epilepsy had DEE of unknown etiology. Disease-causing genetic variants were found in 15/33 (45%) included patients. Three had potentially treatable metabolic disorders (SLC2A1, COQ4 and SLC6A8). Developmental comorbidity was higher in the group with a genetic diagnosis, compared to those who remained undiagnosed. Five novel variants in known genes were found, and the patient phenotypes are described.ConclusionThe results from this study illustrate the importance of performing updated genetic investigations and/or analyses in patients with DEE of unknown etiology. A genetic cause was identified in 45% of the patients, and three of these patients had potentially treatable conditions where available targeted therapy may improve patient outcome.

We recently demonstrated that the consumption of mixed tree nuts (MTNs) as part of a hypocaloric diet decreased heart rate and increased satiety. MTNs can be categorized as a high tryptophan (Trp) food and disturbed Trp metabolism has been associated with cardiovascular disease. The fiber and polyphenol content of MTNs have been suggested to affect human health in part through the gut microbiome. Here, we aim to investigate the effect of MTNs on Trp metabolism and the gut microbiome and the link to cardiovascular markers and satiety. Stool and plasma samples at baseline, week 12 and 24 from our recent randomized, controlled, two-arm study were studied. In the study 95 overweight individuals consuming 1.5 oz. of MTNs (n = 56) or pretzel snack (n = 38) daily as part of a hypocaloric (−500 kcal) weight loss diet for 12 weeks followed by an isocaloric weight maintenance program for additional 12 weeks. Trp metabolites kynurenine (KYN), kynurenic acid (KYNA), Trp, indole sulfate (IS), indole propionate (IPA) and indole acetate (IAA) were analyzed by LC-MS and HPLC. Gut microbiota will be analyzed by 16S rRNA sequencing. At baseline, a positive correlation was observed between heart rate and serum KYN levels and KYN/Trp ratio, as well as between BMI and KYN/Trp ratio. Compared to baseline, KYN levels were significantly reduced in the MTN group at the end of 12 week weight loss phase (P = 0.04) and returned to baseline concentration after 12 weeks of isocaloric weight maintenance program (baseline vs. week 12 vs. week 24: 357 ± 124 vs. 339 + 103 vs. 362 ± 137 ng/mL), but not in pretzel group (418 + 431 vs. 347 ± 150 vs. 375 + 171 ng/mL). Other Trp metabolites evaluatedwere not changed during intervention in either groups. The gut microbiome analysis is ongoing. We identified a positive association between Try-KYN metabolism and heart rate and BMI in overweight individuals. MTN consumption may directly affect Trp-KYN metabolism. International Tree Nut Council Nutrition Research and Education Foundation.

Kombucha is an increasingly popular functional beverage that has gained attention for its unique combination of phytochemicals, metabolites, and microbes. Previous chemical and microbial composition analyses of kombucha have mainly focused on understanding their changes during fermentation. Very limited information is available regarding nutrient profiles of final kombucha products in the market. In this study, we compared the major chemicals (tea polyphenols, caffeine), antioxidant properties, microbial and metabolomic profiles of nine commercial kombucha products using shotgun metagenomics, internal transcribed spacer sequencing, untargeted metabolomics, and targeted chemical assays. All of the nine kombucha products showed similar acidity but great differences in chemicals, metabolites, microbes, and antioxidant activities. Most kombucha products are dominated by the probiotic Bacillus coagulans or bacteria capable of fermentation including Lactobacillus nagelii, Gluconacetobacter, Gluconobacter, and Komagataeibacter species. We found that all nine kombuchas also contained varying levels of enteric bacteria including Bacteroides thetaiotamicron, Escherischia coli, Enterococcus faecalis, Bacteroides fragilis, Enterobacter cloacae complex, and Akkermansia muciniphila. The fungal composition of kombucha products was characterized by predominance of fermenting yeast including Brettanomyces species and Cyberlindnera jadinii. Kombucha varied widely in chemical content assessed by global untargeted metabolomics, with metabolomic variation being significantly associated with metagenomic profiles. Variation in tea bases, bacteria/yeast starter cultures, and duration of fermentation may all contribute to the observed large differences in the microbial and chemical profiles of final kombucha products.

Mixed tree nuts (MTNs) are an excellent source of protein and healthy fat contributing to satiety. However, their relatively high caloric content might not be beneficial in a weight loss diet. The present study was designed to test whether including MTNs in a weight loss and maintenance program interferes with weight management compared to a refined carbohydrate pretzel snack (PS). We performed a randomized, controlled, two-arm study in 95 overweight individuals consuming 1.5 oz of MTNs or PS daily as part of a hypocaloric weight loss diet (−500 kcal) over 12 weeks followed by an isocaloric weight maintenance program for 12 weeks. Participants in both groups experienced significant weight loss (12 weeks: −1.6 and −1.9 and 24 weeks: −1.5 and −1.4 kg) compared to baseline in the MTN and PS groups, respectively. However, there was no difference in weight loss and other outcome parameters between the MTN and PS groups. The MTN group showed a significant increase in satiety at 24 weeks. Both groups had a decrease in diastolic blood pressure at 12 weeks. Participants in the MTN group showed significant decreases in heart rate at 4, 12, and 24 weeks. Plasma oleic acid was significantly increased at 12 and 24 weeks in the MTN group but only at 12 weeks in the PS group. Plasma MCP-1 was decreased significantly in the MTN group at 4 weeks. In summary, participants in both groups lost weight, but only the MTN intervention increased satiety at 24 weeks, enhanced retention, decreased heart rate, and increased serum oleic acid at 24 weeks.