{"slug":"vip-ibd","verification":{"valid":true,"entries":1,"head":"9e77f76cd4856e628f36d3959103976cd6901a0b2ca51a65441ee0e0e0af165c"},"count":1,"models":["grok/grok-4.3"],"yield":{"passes":1,"energy_spent_rows":0,"total_cost_usd":0.025834,"waste_cost_usd":0,"total_tokens":17760,"material_outputs":0,"usd_per_output":null,"models":[{"model":"grok/grok-4.3","passes":1,"cost_usd":0.025834,"tokens_total":17760,"outputs":0,"waste_passes":0,"usd_per_output":null}],"constraints":{"constitution":"/api/articles/constitution","collaborate_schema":"POST /api/protocol/collaborate","pricing_ppm":{"grok-4.3":[1.25,2.5],"grok/grok-4.3":[1.25,2.5],"grok-build-0.1":[1,2],"kimi/moonshot-v1-8k":[0.15,0.15],"gemini/gemini-2.5-flash":[0.075,0.3],"gemini/gemini-2.0-flash-lite":[0.075,0.3],"openai/gpt-4o":[2.5,10],"openai/gpt-4o-mini":[0.15,0.6],"system/reflex":[0,0],"ingest:deterministic":[0,0],"fill-slots":[0,0]}}},"contributions":[{"seq":0,"id":"k1","ts":"2026-06-29T22:29:35.771Z","model":"grok/grok-4.3","role":"writer","action":"redraft","payload":{"title":"VIP for IBD: Evidence Graded Review of Vasoactive Intestinal Peptide in Crohn's Disease and Colitis","register":"source_ledger","body":"## What's breaking down if you have IBD (Crohn's / colitis)\n\nIf your intestinal lining loses barrier integrity, immune cells over-respond and inflammation persists. Epithelial cells fail to repair quickly enough. Nerve signaling in the gut wall shifts. These layers compound: barrier leak allows more triggers, immune imbalance sustains damage, and autonomic control of motility and secretion falters. Regeneration falls behind degeneration, so the condition continues.\n\n## Why VIP might help you\n\n1. You are reading about IBD (Crohn's / colitis) — what breaks down matters before any compound name.\n2. Therefore for you: If the immune / autonomic layer is part of your problem, VIP is discussed because it targets repair (tissue) — not because it masks pain.\n\nIf immune over-activation drives your mucosal damage, VIP pathways connect to reduced pro-inflammatory signals and better epithelial recovery in studied models. If autonomic imbalance affects gut motility or secretion, VIP's natural role in those systems aligns with restoring balance rather than suppression alone.\n\n## How these fit together\n\nSingle-compound focus — if your condition profile includes a multi-peptide stack, siblings target other layers listed in the condition profile.\n- VIP → immune / autonomic\n\n## What the evidence actually shows\n\nHuman data: Observational only. One cross-sectional and prospective study of 115 adults with IBD measured VIP concentrations and found variable plasma levels that differed by disease severity (source s1). Another examined VIP nerves in Crohn's tissue and noted consistent increases and abnormal appearance in rectal samples (source s2). These show associations, not treatment effects.\n\nPreclinical data: Multiple mouse and rat studies. In TNBS-induced colitis (model sharing features with Crohn's), VIP treatment reduced clinical signs including weight loss, diarrhea, and histologic inflammation (source s3). VIP nanomedicine in DSS and TNBS mouse colitis lowered pro-inflammatory cytokines, improved histology, and supported tight junction proteins (source s4). VIP-deficient mice showed greater susceptibility to chemically induced colitis in some experiments, with exogenous VIP rescuing barrier features (source s5). Results are mixed across studies; some report exacerbation depending on model and microbiota (source s5).\n\nAnecdotal data: Limited. One Reddit thread states VIP is among the better researched compounds for Crohn's via upstream immune effects on gut lining (source s6). Other posts discuss VIP in unrelated contexts such as CIRS or Raynaud's with no IBD-specific outcomes reported.\n\n## What scientists say\n\nResearchers note VIP's immunomodulatory properties in colitis models and suggest it as a candidate for further testing in Crohn's, while highlighting inconsistent findings in knockout models and human expression data (sources s3, s5). Emphasis remains on preclinical promise rather than clinical translation.\n\n## What people say on Reddit\n\nDiscussions are sparse. Users mention VIP's anti-inflammatory profile and one notes specific research interest in Crohn's. No detailed personal outcome reports tied to IBD treatment appear in top results.\n\n## What people say on X\n\nNo relevant patient experiences or outcome reports surfaced in searches for VIP in IBD contexts.\n\n## What we do not know\n\nNo published human intervention trials test VIP administration for IBD symptom control or mucosal healing. Optimal delivery, duration, and patient selection remain untested in controlled settings. Long-term effects on human gut microbiota or barrier repair are unknown.\n\n## Safety and limits\n\nVIP is a naturally occurring peptide with documented effects in animal colitis models, but human safety data for therapeutic use in IBD do not exist in the reviewed sources. Observational human studies report no direct safety signals from measurement alone. All therapeutic claims rest on preclinical work.","claims":[{"id":"c1","text":"VIP treatment reduced clinical and histologic severity in TNBS-induced colitis in mice.","section":"What the evidence actually shows","tier":"preclinical","source_ids":["s3"],"source_status":"sourced","why_material":"Direct evidence of repair pathway effects in a Crohn's-like model.","evidence_basis":"derived_inference","weight":0.5,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"slot":null,"who_claims":"grok/grok-4.3","posted_by":{"actor":"grok/grok-4.3","channel":"protocol/draft","ts":"2026-06-29T22:29:34.913Z","model":"grok/grok-4.3","rationale":""},"extra":{}},{"id":"c2","text":"VIP nanomedicine lowered inflammation markers and improved barrier proteins in DSS and TNBS mouse colitis.","section":"What the evidence actually shows","tier":"preclinical","source_ids":["s4"],"source_status":"sourced","why_material":"Shows tissue-level repair signals beyond symptom masking.","evidence_basis":"derived_inference","weight":0.5,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"slot":null,"who_claims":"grok/grok-4.3","posted_by":{"actor":"grok/grok-4.3","channel":"protocol/draft","ts":"2026-06-29T22:29:34.913Z","model":"grok/grok-4.3","rationale":""},"extra":{}},{"id":"c3","text":"VIP plasma levels vary with IBD severity in a study of 115 patients.","section":"What the evidence actually shows","tier":"human","source_ids":["s1"],"source_status":"sourced","why_material":"Observational association only; no treatment data.","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"slot":null,"who_claims":"grok/grok-4.3","posted_by":{"actor":"grok/grok-4.3","channel":"protocol/draft","ts":"2026-06-29T22:29:34.913Z","model":"grok/grok-4.3","rationale":""},"extra":{}},{"id":"c4","text":"VIP nerve changes observed in Crohn's rectal tissue samples.","section":"What the evidence actually shows","tier":"human","source_ids":["s2"],"source_status":"sourced","why_material":"Tissue-level observation in patients.","evidence_basis":"derived_inference","weight":0.8,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"slot":null,"who_claims":"grok/grok-4.3","posted_by":{"actor":"grok/grok-4.3","channel":"protocol/draft","ts":"2026-06-29T22:29:34.913Z","model":"grok/grok-4.3","rationale":""},"extra":{}},{"id":"c5","text":"VIP-deficient mice exhibit increased susceptibility to chemically induced colitis in some models.","section":"What the evidence actually shows","tier":"preclinical","source_ids":["s5"],"source_status":"sourced","why_material":"Supports role in barrier maintenance.","evidence_basis":"derived_inference","weight":0.5,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"slot":null,"who_claims":"grok/grok-4.3","posted_by":{"actor":"grok/grok-4.3","channel":"protocol/draft","ts":"2026-06-29T22:29:34.913Z","model":"grok/grok-4.3","rationale":""},"extra":{}},{"id":"c6","text":"Reddit users note VIP research relevance to Crohn's via immune effects on gut lining.","section":"What people say on Reddit","tier":"anecdotal","source_ids":["s6"],"source_status":"sourced","why_material":"Community discussion, not outcome data.","evidence_basis":"derived_inference","weight":0.3,"status":"active","stance_scores":{"neutral":0,"pro":0,"adversary":0},"slot":null,"who_claims":"grok/grok-4.3","posted_by":{"actor":"grok/grok-4.3","channel":"protocol/draft","ts":"2026-06-29T22:29:34.913Z","model":"grok/grok-4.3","rationale":""},"extra":{}}],"sources":[{"id":"s1","type":"pubmed","url":"https://pubmed.ncbi.nlm.nih.gov/2791804/","title":"Vasoactive intestinal peptide as a laboratory supplement to clinical testing in inflammatory bowel disease","quote":"One hundred-fifteen adult IBD patients were studied cross-sectionally and prospectively, 48 with ulcerative colitis (UC) and 67 with Crohn's disease (CD).","link_status":"ok","quote_status":"verified"},{"id":"s2","type":"pubmed","url":"https://gut.bmj.com/content/25/1/57","title":"Vasoactive intestinal peptide concentrations and immunocytochemistry in the colon of patients with Crohn's disease","quote":"Immunocytochemistry revealed a consistent increase in, and abnormal appearance of, VIP nerves in patients with Crohn's disease not only those with rectal...","link_status":"http_403","quote_status":"unverified"},{"id":"s3","type":"pubmed","url":"https://www.gastrojournal.org/article/S0016-5085(03)00055-6/fulltext","title":"Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease","quote":"Treatment with VIP reduced the clinical and histopathologic severity of TNBS-induced colitis, abrogating body weight loss, diarrhea, and macroscopic and microscopic intestinal inflammation.","link_status":"http_403","quote_status":"unverified"},{"id":"s4","type":"pubmed","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC6053281/","title":"Vasoactive Intestinal Peptide Nanomedicine for the Treatment of Inflammatory Bowel Disease","quote":"We demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD.","link_status":"ok","quote_status":"verified"},{"id":"s5","type":"pubmed","url":"https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02689/full","title":"Vasoactive Intestinal Peptide Deficiency Is Associated With Dysbiosis and Altered Short-Chain Fatty Acid Levels in the Gastrointestinal Tract","quote":"In some studies, VIP knockout mice were more susceptible to chemically-induced intestinal inflammation, and human inflammatory bowel disease (IBD) patients show a reduction in VIP positive nerves proximal to severe mucosal damage.","link_status":"ok","quote_status":"verified"},{"id":"s6","type":"reddit","url":"https://www.reddit.com/r/Biohack_Blueprint/comments/1u31ihv/the_peptide_nobody_talks_about_but_everyone/","title":"The peptide nobody talks about but everyone should: VIP","quote":"VIP is actually one of the better researched compounds for Crohn's specifically. it works upstream on the immune response in the gut lining ...","link_status":"ok","quote_status":"unverified"}]},"rationale":"","tokens_in":14853,"tokens_out":2907,"cost":0.02583375,"prev_hash":"genesis","hash":"9e77f76cd4856e628f36d3959103976cd6901a0b2ca51a65441ee0e0e0af165c"}]}