Irritable Bowel Syndrome (IBS)
Rome IV functional bowel disorder of brain-gut interaction — IBS-D (diarrhea predominant), IBS-C (constipation), IBS-M (mixed), IBS-U (unsubtyped) — distinct from IBD, microscopic colitis, and celiac disease. Diagnosis of exclusion: rule out organic disease (celiac serology, fecal calprotectin to distinguish from IBD, TSH, CBC, CRP, age-appropriate colonoscopy). ACG 2021 + AGA 2022 evidence-graded ladder: low-FODMAP elimination (Monash University protocol), subtype-targeted pharmacotherapy (rifaximin / Xifaxan FDA 2015 IBS-D, eluxadoline / Viberzi 2015 with pancreatitis warning in cholecystectomy patients, alosetron / Lotronex REMS-restricted; linaclotide / Linzess, plecanatide / Trulance, lubiprostone, tegaserod re-approved 2019 for women <65 for IBS-C), neuromodulator-dose TCAs/SSRIs, CBT-GI, gut-directed hypnotherapy, peppermint oil (BSG-recommended). The editorial honest answer for this trigger is that no peptide in the Juno library has a defensible discovery-card case — BPC-157 'leaky gut' community framing applies a mucosal-injury-repair mechanism to a functional brain-gut-axis disorder where the lesion isn't mucosal injury.
What changes during this transition
IBS is a Rome IV symptom-criteria diagnosis: recurrent abdominal pain associated with defecation, change in stool frequency, or change in stool form — present at least one day per week over three months. It is sub-typed by predominant stool form (IBS-D diarrhea, IBS-C constipation, IBS-M mixed, IBS-U unsubtyped) and is a diagnosis of exclusion: celiac serology (tTG-IgA + total IgA), fecal calprotectin (to distinguish from IBD), TSH, CBC, CRP, and age-appropriate colonoscopy come first. IBS is distinct from IBD (covered as the `ibd` axis), microscopic colitis, and celiac disease — the disease-boundary distinctions are editorially load-bearing because community peptide framing routinely blurs them. The established evidence-graded ladder per ACG 2021 and AGA 2022: Diet: low-FODMAP elimination + structured reintroduction (Monash University protocol), dietitian-supervised. Strongest dietary evidence in IBS. IBS-D pharmacotherapy: rifaximin (Xifaxan — FDA-approved 2015 specifically for IBS-D), eluxadoline (Viberzi 2015 — black-box pancreatitis warning in post-cholecystectomy patients), alosetron (Lotronex — REMS-restricted), neuromodulator-dose TCAs (10-25 mg amitriptyline qhs). IBS-C pharmacotherapy: linaclotide (Linzess), plecanatide (Trulance), lubiprostone (Amitiza), tegaserod (re-approved 2019 for women <65), PEG laxatives, SSRIs at neuromodulator doses for visceral pain. Mind-body (brain-gut axis): CBT-GI (gut-directed cognitive behavioral therapy) and gut-directed hypnotherapy are both AGA 2022-endorsed with strong evidence; peppermint oil is BSG-recommended. Peptides do not appear in ACG 2021 or AGA 2022. The community-most-common pitch — BPC-157 for 'leaky gut' / 'gut healing' — applies a mucosal-injury-repair mechanism to a functional bowel disorder where the lesion isn't mucosal injury. The 'leaky gut causes IBS' hypothesis is not validated — increased intestinal permeability has been observed in subsets of IBS-D patients, but causality (and whether normalizing permeability changes symptoms) is unestablished. The rodent colitis models BPC-157 is studied in (DSS, TNBS) are IBD models, not IBS models. The brain-gut axis framing is real and well-established — but the established interventions for it are CBT-GI, gut-directed hypnotherapy, and neuromodulator-dose TCAs/SSRIs, not peptides. IBS + GAD comorbidity runs 40-60% in the gastroenterology literature, which is why ACG 2021 and AGA 2022 both endorse neuromodulator-dose antidepressants and mind-body therapies. Where Juno's library fits — narrowly and with deliberate non-elevation. No peptide has a discovery-card-defensible IBS case. The five drafted substrate entries (BPC-157, KPV, Larazotide, Selank, DSIP) exist for honest /ask answers when users probe specific compounds. BPC-157's 'gut healing' framing is the largest community application but applies IBD-rodent-model mechanism work to a functional disorder. KPV's α-MSH anti-inflammatory framing is in IBD models, not IBS. Larazotide's most-developed program (CeD-LIFT in non-responsive celiac) failed Phase 3, and there is no completed IBS trial. Selank addresses the anxiety-comorbidity overlay (40-60% IBS-GAD prevalence) but CBT-GI / gut-directed hypnotherapy / neuromodulator-dose TCAs are the guideline-endorsed answers for the same overlap. DSIP gets pitched on the sleep-IBS overlap but the original sleep program never converged on a reliable effect, and low-dose amitriptyline (10-25 mg qhs) addresses sleep + IBS-D in a single intervention with guideline support.
Important caveat
IBS is gastroenterology-managed standard-of-care disease — Rome IV symptom-criteria diagnosis of exclusion is the LOAD-BEARING PRECONDITION. Rule out organic disease BEFORE accepting IBS as the diagnosis: celiac serology (tTG-IgA + total IgA, ideally on a gluten-containing diet; biopsy if seropositive), fecal calprotectin (to distinguish IBS from IBD — load-bearing because peptide-community framing routinely blurs the boundary), TSH, CBC, CRP, age-appropriate colonoscopy. No peptide substitutes for this workup. The established evidence-graded ladder per ACG 2021 and AGA 2022: structured low-FODMAP elimination + reintroduction with a GI dietitian (Monash University protocol) is the strongest dietary evidence. IBS-D pharmacotherapy: rifaximin (Xifaxan, FDA-approved 2015 for IBS-D), eluxadoline (Viberzi 2015, black-box pancreatitis warning in cholecystectomy patients — confirm gallbladder status before considering), alosetron (Lotronex, REMS-restricted), neuromodulator-dose TCAs (10-25 mg amitriptyline qhs — dual action on IBS-D and sleep is editorially efficient). IBS-C pharmacotherapy: linaclotide (Linzess), plecanatide (Trulance), lubiprostone (Amitiza), tegaserod (re-approved 2019 for women <65), PEG laxatives, SSRIs at neuromodulator doses. Mind-body (brain-gut axis): CBT-GI and gut-directed hypnotherapy are both AGA 2022-endorsed with strong evidence — these are Tier 1 for the brain side of the axis; peppermint oil is BSG-recommended. Red flags requiring colonoscopy / urgent workup before accepting IBS: age >50 with new symptoms, rectal bleeding, iron deficiency anemia, unintentional weight loss, family history of CRC or IBD, nocturnal symptoms, fever, palpable abdominal mass. No Juno library peptide is surfaced as an IBS discovery card — BPC-157, KPV, Larazotide, Selank, and DSIP are substrate-only. Rule 6 non-propagation: BPC-157's Sikiric Croatian DSS/TNBS rodent colitis corpus is in IBD models, NOT IBS — IBD and IBS are different diseases with different lesions, and rodent structural-inflammation models do NOT propagate to a functional brain-gut-axis disorder; KPV's α-MSH colitis preclinical work is also in IBD models; Larazotide's CeD-LIFT Phase 3 in celiac did NOT meet primary endpoint and does NOT propagate to IBS where there is no comparable trial; Selank's Russian GAD/neurasthenia registration does NOT propagate to IBS treatment — only to the comorbidity-overlay framing, and CBT-GI / TCAs / SSRIs are the guideline-endorsed answers; DSIP's 1970s-80s Schoenenberger/Monnier sleep work never converged on reliable effect and there is no IBS data. Brain-gut axis is real, IBS is real, and the things that move IBS reliably are in the guidelines. The 'leaky gut causes IBS' hypothesis is not validated; zonulin serum levels and lactulose-mannitol ratio are research tools, not clinical-decision-making diagnostics for IBS. SSRI/SNRI interaction warning for Selank consideration. WADA athletes: BPC-157 (S0) prohibited at all times. Pregnancy: IBS pharmacotherapy options are limited (rifaximin minimal systemic absorption; eluxadoline limited data; TCAs require maternal-fetal medicine coordination); low-FODMAP elimination is generally safe; CBT-GI and gut-directed hypnotherapy are first-line non-pharmacologic in pregnancy.
Want this list to grow? The library is editorial — if there’s a peptide you think belongs on this page with documented or mechanistically-clear evidence, send us a note with the citation and we’ll review it under the same evidence-tier discipline as every other entry.