Functional GI disorders (IBS, dysmotility)

What changes during this transition

Functional GI disorders are Rome IV symptom-based diagnoses without structural or inflammatory pathology — and that diagnostic frame shapes how every peptide question gets answered. The ACG and AGA 2021 IBS guidelines, plus the Rome IV functional dyspepsia framework, anchor the standard-of-care ladder this trigger respects: dietary intervention first (low-FODMAP elimination-reintroduction has Tier 1 trial backing from Halmos 2014 Gastroenterology and successors, ideally with registered-dietitian supervision since long-term restrictive low-FODMAP carries microbiome and quality-of-life costs); enteric-coated peppermint oil for IBS-mixed and abdominal-pain-dominant; antispasmodics (hyoscine, dicyclomine) for cramping; neuromodulators at gut-directed doses (low-dose tricyclics — amitriptyline, nortriptyline — for IBS-D and visceral hypersensitivity; SSRIs for IBS-C and comorbid mood, per Ford 2014 meta-analysis); rifaximin (Xifaxan) for IBS-D and SIBO-positive cases, with the TARGET-1, TARGET-2, TARGET-3 trial program as the regulatory anchor; linaclotide, plecanatide, and lubiprostone for IBS-C; eluxadoline for IBS-D; prokinetics (metoclopramide short-term, prucalopride for chronic constipation). CBT and gut-directed hypnotherapy have Tier 1 evidence for IBS — both deserve to be in the conversation alongside any pharmacologic intervention. The peptides surfaced here are the ones with the most concrete editorial cases for functional GI specifically — and BPC-157 is the centerpiece. This is the closest BPC-157 gets to its actual research base: the Sikiric group's 30+ year published program out of Zagreb is primarily gastrointestinal, covering gastric mucosal protection, intestinal motility, and the colitis models that anchor the IBD substrate. Community framing for 'BPC for gut' tracks closer to the actual preclinical evidence than community framing for any other indication — but Rome IV functional GI is symptom-based without inflammatory pathology, and zero published human IBS or functional dyspepsia RCT of BPC-157 exists. The editorial register shifts from 'community runs ahead of evidence' to 'this is BPC's primary research domain, not extrapolation' — and the gap between rodent gastric/motility evidence and human functional-GI symptom benefit still requires honest naming. KPV carries for the mast-cell-overlap IBS-D subset — α-MSH C-terminal lineage with preclinical mast-cell-stabilization mechanism is most concrete in the MCAS-overlap and post-infectious-IBS subgroups where mucosal mast-cell hyperplasia is documented. Larazotide is the closest pharmaceutical lever to the 'leaky gut' hypothesis of IBS — the contested 9 Meters Phase 3 program in celiac matters editorially, and Rule 6 keeps celiac evidence from propagating to IBS. B12-methylcobalamin carries for the chronic-PPI, metformin, and post-bariatric subgroups where confirmed deficiency is common in functional-GI patient populations — established medicine for repletion, not treatment for functional GI per se. What's NOT surfaced as a discovery card: thymosin alpha-1. The community framing of 'immune dysregulation in post-infectious IBS' and 'SIBO-associated immune issues' is mechanism-extrapolation that runs backwards from the actual immunology — Th1-augmentation in a population with mucosal mast-cell and T-cell hyperactivity is directionally wrong, and TA-1's HBV/HCV/sepsis approval doesn't propagate per Rule 6. Substrate-only for honest answers at /ask, not surfaced as discovery. The IBD vs functional GI distinction matters editorially across this whole trigger: IBD (Crohn's, UC) is autoimmune-inflammatory disease with mucosal lesions, biologic-managed; functional GI is Rome IV symptom-based without inflammatory pathology. Evidence between the two domains does not propagate. The MCAS-overlap functional-GI subgroup is editorially distinct from the mast-cell-activation trigger (which is the broader multi-system MCAS picture). Post-Lyme GI overlap is touched in the chronic-Lyme trigger; this is primary functional GI, not infection-driven.