The use of natural products and derivatives for the prevention and control of non-communicable chronic diseases, such as type-2 diabetes (T2D), obesity, and hepatic steatosis is a way to achieve homeostasis through different metabolic pathways. Thus, male C57BL/6 mice were divided into the following groups: high-fat diet (HFD) vehicle, HFD + Supplemented, HFD + Supplemented_S, and isolated compounds. The vehicle and experimental formulations were administered orally by gavage once a day over the four weeks of the diet (28 consecutive days). We evaluated the energy homeostasis, cytokines, and mitochondrial gene expression in these groups of mice. After four weeks of supplementation, only the new nutraceutical group (HFD + Supplemented) experienced reduced fasting glycemia, insulin, HOMA index, HOMA-β, dyslipidemia, ectopic fat deposition, and hepatic fibrosis levels. Additionally, the PPARγ coactivator 1 α (Pgc-1α), interleukin-6 (Il-6), and interleukin-10 (Il-10) gene expression were augmented, while hepatic steatosis decreased and liver parenchyma was recovered. The glutathione-S-transferase activity status was found to be modulated by the supplement. We discovered that the new nutraceutical was able to improve insulin resistance and hepatic steatosis mainly by regulating IL-6, IL-10, and Pgc-1α gene expression.

Stress, unhealthy lifestyle, and sleep disturbance worsen cognitive function in mood disorders, prompting a rise in the development of integrative health approaches. The recent investigations in the gut–brain axis field highlight the strong interplay among microbiota, inflammation, and mental health. Thus, this study aimed to investigate a new nutraceutical formulation comprising prebiotics, minerals, and silymarin’s impact on microbiota, inflammation, mood, and sleep quality. The study evaluated the LL1 + silymarin capsule supplementation over 180 days in overweight adults. We analyzed the fecal gut microbiota using partial 16S rRNA sequences, measured cytokine expression via CBA, collected anthropometric data, quality of life, and sleep questionnaire responses, and obtained plasma samples for metabolic and hormonal analysis at baseline (T0) and 180 days (T180) post-supplementation. Our findings revealed significant reshaping in gut microbiota composition at the phylum, genus, and species levels, especially in the butyrate-producer bacteria post-supplementation. These changes in gut microbiota were linked to enhancements in sleep quality, mood perception, cytokine expression, and anthropometric measures which microbiota-derived short-chain fatty acids might enhance. The supplementation tested in this study seems to be able to improve microbiota composition, reflecting anthropometrics and inflammation, as well as sleep quality and mood improvement.

Background/Objectives: Long-term evidence on microbiome-targeted nutraceuticals in inflammatory bowel disease (IBD) is limited; we evaluated two regimens over 12 months. Methods: In this single-center, double-blind, nonrandomized, two-arm pilot trial, patients with ulcerative colitis (UC) or Crohn’s disease (CD) on stable standard-of-care therapy received fructooligosaccharides, galactooligosaccharides, yeast β-glucan, and minerals, alone (Suppl) or with silymarin (Suppl Plus), and were assessed at baseline, 6, and 12 months. The primary outcome was remission or mild activity at 12 months (UC, Mayo endoscopic subscore; CD, Simple Endoscopic Score for Crohn’s Disease). Secondary outcomes included fecal calprotectin, C-reactive protein (CRP), 16S rRNA gene profiles, and fecal nuclear magnetic resonance metabolomics. Registration: Brazilian Registry of Clinical Trials, RBR-7hvd26h. Results: Of 87 participants enrolled, 75 completed follow-up (UC, n=50; CD, n=25); four died. In UC, remission or mild activity increased from 44.0% to 82.0% (p<0.001), and median calprotectin declined from 406 to 286 µg/g (p=0.046); CRP was unchanged. In CD, it remained 88.0% (p=1.000), without calprotectin change (p=0.968). Remission did not differ between arms (UC, p=1.000; CD, p=0.593). Among completers, gastrointestinal adverse effects were self-limited; flatulence increased from 2.7% to 16.0% (p=0.009). Genus-level α-diversity increased, and Dorea and Blautia were enriched in UC at 6 months; community structure did not differ between arms. In UC, fecal xanthine (+139%), 4-pyridoxate (+130%), and nicotinate (+105%) increased. Conclusions: In this nonrandomized, single-center pilot without placebo, 12-month supplementation was associated with increased remission and reduced fecal calprotectin in UC; silymarin conferred no significant advantage. Randomized, placebo-controlled, multicenter trials are warranted.