Obesity is a costly and ongoing health complication in the United States and globally. Bioactive-rich foods, especially those providing polyphenols, represent an emerging and attractive strategy to address this issue. Berry-derived anthocyanins and their metabolites are of particular interest for their bioactive effects, including weight maintenance and protection from metabolic aberrations. Earlier findings from small clinical trials suggest modulation of substrate oxidation and glucose tolerance with mediation of prospective benefits attributable to the gut microbiota, but mixed results suggest appropriate anthocyanin dosing poses a challenge. The objective of this randomized, placebo-controlled study was to determine if anthocyanin-dense elderberry juice (EBJ) reproduces glucoregulatory and substrate oxidation effects observed with other berries and if this is mediated by the gut microbiota. Overweight or obese adults (BMI > 25 kg/m²) without chronic illnesses were randomized to a 5-week crossover study protocol with two 1-week periods of twice-daily EBJ or placebo (PL) separated by a washout period. Each treatment period included 4 days of controlled feeding with a 40% fat diet to allow for comparison of measurements in fecal microbiota, meal tolerance testing (MTT), and indirect calorimetry between test beverages. Eighteen study volunteers completed the study. At the phylum level, EBJ significantly increased Firmicutes and Actinobacteria, and decreased Bacteroidetes. At the genus level, EBJ increased Faecalibacterium, Ruminococcaceae, and Bifidobacterium and decreased Bacteroides and lactic acid-producing bacteria, indicating a positive response to EBJ. Supporting the changes to the microbiota, the EBJ treatment significantly reduced blood glucose following the MTT. Fat oxidation also increased significantly both during the MTT and 30 min of moderate physical activity with the EBJ treatment. Our findings confirm the bioactivity of EBJ-sourced anthocyanins on outcomes related to gut health and obesity. Follow-up investigation is needed to confirm our findings and to test for longer durations.

Microalgae, a marine-derived natural ingredient, has emerged as a rich source of bioactive compounds with the potential to modulate gut–brain axis activities. The objective of this study was to investigate whether supplementation with a microalgae extract from Tetradesmus obliquus strain Mi175.B1.a (TOME) influences gut health and reduces stress and anxiety in healthy adults experiencing mild to moderate gastrointestinal (GI) distress. Methods: Fifty-six healthy adults (age: 31.9 ± 7.7 years; body weight: 71.8 ± 12.6 kg; BMI: 24.6 ± 2.8 kg/m²) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arm clinical trial. Participants were randomly allocated to receive capsules containing either 250 mg/day of TOME or a placebo for four weeks. Primary outcomes included the assessment of GI symptoms using the Gastrointestinal Symptom Rating Scale (GSRS) and Bristol Stool Scale (BSS). Secondary outcomes focused on subjective evaluation of mood, stress, and anxiety, as well as blood pressure responses to sympathetic nervous system activation induced by the cold pressor test (CPT). In addition, stool, plasma, and saliva samples were collected to assess biomarkers associated with stress, sympathetic activation, intestinal permeability, and GI health. 16S rRNA sequencing was performed to analyze changes in gut microbial populations. Results: Daily supplementation for four weeks with TOME was safe and well tolerated in the study population. In addition, TOME significantly reduced GSRS global scores (p = 0.02), as well as constipation (p = 0.05) and indigestion (p = 0.03) subcomponent scores compared to Placebo. There was also a significant increase in Shannon’s index before FDR correction (p = 0.05; FDR = 0.12) and stool butyrate level was significantly lower in the TOME group than in Placebo after 4 weeks of supplementation (p = 0.039). Both groups showed a significant reduction in perceived stress scores, but the TOME intervention group also had reduced Negative Affect scores (p < 0.001). In addition, plasma chromogranin A, a stress biomarker, was significantly reduced after TOME intervention (p = 0.03). There were no negative effects on blood lipids or other parameters related to sympathetic activation or cardiovascular health. Conclusions: Overall, these results suggest that 4-week supplementation with T. obliquus strain Mi175.B1.a improves GI symptoms, potentially through effects on the gut microbiota, and may promote positive effects on mental health. Additional research should follow up on mental health outcomes in populations with increased stress and anxiety and investigate mechanisms underlying improvements in GI health. This trial was registered at clinicaltrials.gov as NCT06425094.