Purpose: Cancer-associated cachexia (CC) is characterized by involuntary weight loss and poor prognosis. Central nervous system (CNS) inflammation has been linked to CC symptoms. This study evaluated inflammatory mediators in the cerebrospinal fluid (CSF) of patients with CC. Methods: Volunteers were recruited in Santarém, PA, Brazil, and divided into three groups: patients undergoing herniorrhaphy or cholecystectomy (n = 43)—control; cancer without cachexia (CWC, n = 13); and CC (n = 49). Blood and CSF were collected before anesthetic injection. Results: CSF vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1) levels were reduced in CC (p < 0.0001; p 0.00017) and CWC (p = 0.0269; p = 0.0421) compared to control. CSF IP-10 was lower in CC (p = 0.0048). In CWC, CSF MCP-1 correlated with serum C reactive protein (rs = 0.78, p = 0.0098), leukocytes (rs = 0.72, p = 0.0235), lymphocytes (rs = -0.67, p = 0.0390) and monocytes (rs = -0.82, p = 0.0058). In CC, CSF interleukin (IL)-8 correlated with leukocytes (rs = 0.48, p = 0.0032) and MCP-1 with neutrophils (rs = 0.36, p = 0.0265) and eosinophils (rs = -0.37, p = 0.0218). CC patients showed lower quality of life than CWC (functional scale p = 0.0087; symptoms scale p = 0.0386). Conclusion: Cancer was related to changes in CSF cytokine levels, indicating that both tumor presence and cachexia modulate central inflammatory signaling. Correlations between CSF chemokines and blood immune cells suggest systemic interaction between peripheral immunity and the CNS.

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.