IBD / leaky gut
Barrier breakdown with mucosal inflammation; rebuild barrier, dampen flare.
Decision support, not prescription. You decide.
Candidate agents
6 agents · tap to expand▶LarazotideLeadEmergingLarazotide is an oral, gut-restricted zonulin antagonist aimed at the 'leaky gut' half of the IBD problem; the barrier mechanism is well-supported and there is genuine human RCT data in celiac disease, but there is no IBD trial at all, so for IBD it is a preclinical/extrapolated concept rather than proven therapy.expand
Larazotide is an oral, gut-restricted zonulin antagonist aimed at the 'leaky gut' half of the IBD problem; the barrier mechanism is well-supported and there is genuine human RCT data in celiac disease, but there is no IBD trial at all, so for IBD it is a preclinical/extrapolated concept rather than proven therapy.
▸Full clinical story
It is an octapeptide that antagonizes zonulin signaling and promotes tight-junction (ZO-1/occludin) reassembly, reducing paracellular permeability at the epithelial barrier. Because barrier breakdown and antigen leak drive the mucosal inflammatory loop in IBD, tightening junctions is a rational upstream lever, but larazotide targets permeability, not the established inflammatory cascade.
The only human efficacy data are in celiac disease, not IBD: a 342-patient phase 2 double-blind RCT found the 0.5 mg dose reduced symptoms in patients still symptomatic on a gluten-free diet (higher doses failed). Barrier-tightening and reversal of zonulin-driven permeability are confirmed in animal/mechanistic work (e.g., a lupus-microbiome mouse model where oral larazotide fully reversed gut permeability), and reviews position zonulin as a druggable barrier target. There is no completed IBD/leaky-gut clinical trial, and the only condition-relevant efficacy data are animal/mechanistic, so for IBD the honest grade is preclinical — the celiac RCT is supportive but indirect human evidence in a different indication, not IBD evidence.
Anecdotal community signal only: larazotide is discussed in 'leaky gut' and functional-GI circles, but it is not an approved or readily compounded product, so real-world off-label use is limited compared with peptides like BPC-157 or LDN. Reports are sparse and should not be read as efficacy.
Context, not a protocol: the celiac RCT signal was at 0.5 mg three times daily taken before meals, with the counterintuitive finding that higher doses (1-2 mg) lost benefit. No IBD-specific dosing is established.
Being gut-restricted with minimal systemic absorption, it has a clean interaction profile, but the flat/inverted dose-response means 'more' is not better. It addresses permeability only and would not substitute for anti-inflammatory or biologic control of active IBD; supply/availability is a practical limitation since development has been uneven.
A mechanistically attractive barrier-repair candidate with real human RCT data in celiac disease but zero IBD trials and only animal-level evidence for gut permeability in IBD-adjacent models; reasonable to watch as an adjunct concept, not something to position as an IBD treatment today.
- Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. ↗
- Sex-dependent Lupus strain induction of zonulin-mediated intestinal permeability and autoimmunity. ↗
- Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions. ↗
▶BPC-157PreclinicalBPC-157 is a synthetic gastric pentadecapeptide with broad cytoprotective and mucosal-healing effects in rodent GI-injury and colitis models, but human IBD trial data do not exist — it is preclinical, and much of the literature comes from a single research group.expand
BPC-157 is a synthetic gastric pentadecapeptide with broad cytoprotective and mucosal-healing effects in rodent GI-injury and colitis models, but human IBD trial data do not exist — it is preclinical, and much of the literature comes from a single research group.
▸Full clinical story
It is reported to promote angiogenesis and granulation-tissue/epithelial healing, upregulate growth-factor and VEGF pathways, and modulate the NO system and gut-brain axis, which maps onto the barrier-repair arm of the lever. In colitis specifically it is described as cytoprotective and pro-healing across mucosal injury.
Evidence is preclinical: a broad review documents mucosal-protective and healing effects across gastrointestinal injury and ulcerative-colitis rodent models and asserts stability in human gastric juice, but the human 'trials' referenced are limited and largely from the originating group, and no controlled IBD trial exists. Interpret with caution given single-lab dominance and enthusiastic framing; preclinical is the correct grade.
Anecdotal community signal: BPC-157 is among the most widely used gray-market gut-repair peptides, taken orally for GI/IBD complaints and by subcutaneous injection for systemic/tendon indications, with many users reporting symptom relief. This is uncontrolled self-report from unregulated product and is not evidence of efficacy or safety.
Context, not a protocol: community use commonly cites roughly 250-500 mcg once or twice daily, oral for GI targets; there is no validated human dose, purity standard, or long-term safety dataset.
No regulatory approval, no human safety data at scale, and unverified compounding purity are the main flags; the angiogenic/growth-promoting mechanism warrants theoretical caution and it should never replace proven anti-inflammatory therapy in active IBD. Be wary of the promotional tone of much of the primary literature.
Heavy rodent healing signal and huge community enthusiasm, but zero controlled human IBD data and a thin, single-source evidence base — a candidate to watch, clearly labeled experimental.
▶KPVPreclinicalKPV is an alpha-MSH-derived tripeptide with an appealing dual anti-inflammatory/mucosal-healing profile in colitis models, but all supporting data are animal/in-vitro — it is a preclinical candidate, not a validated IBD therapy.expand
KPV is an alpha-MSH-derived tripeptide with an appealing dual anti-inflammatory/mucosal-healing profile in colitis models, but all supporting data are animal/in-vitro — it is a preclinical candidate, not a validated IBD therapy.
▸Full clinical story
As the C-terminal fragment of alpha-MSH, KPV is taken up by intestinal epithelial cells and macrophages (partly via PepT1) where it downregulates NF-kB-driven cytokines such as TNF-alpha and dampens the mucosal inflammatory response. Mechanistically it addresses the inflammation arm of the lever and, in delivery studies, accelerated mucosal healing.
Evidence is preclinical: in a mouse ulcerative colitis model, orally delivered KPV (hyaluronic-acid-functionalized nanoparticles targeting colonic epithelium and macrophages) both accelerated mucosal healing and reduced TNF-alpha, outperforming free/less-targeted formulations. A melanocortin-system review reinforces the biologic rationale but adds no human IBD data. No clinical trials exist, so preclinical is the honest grade.
Anecdotal community signal: KPV appears in peptide-user and functional-medicine gut-repair discussions, sometimes oral and sometimes combined with BPC-157, with users reporting reduced GI inflammation. This is uncontrolled self-report from an unregulated supply and should not be read as efficacy.
Context, not a protocol: no established human dose. Community use centers on oral capsules in the low-milligram range; the animal efficacy hinged heavily on the targeted nanoparticle delivery system, which does not translate to over-the-counter peptide products.
Oral bioavailability and colonic delivery are the central unknowns — the rodent benefit depended on an engineered carrier, not free peptide. Source purity is unverified in the gray market; it should not displace evidence-based IBD control.
A biologically coherent, promising anti-inflammatory tripeptide stuck at the animal-model stage; interesting to track but not something to present to patients as an established IBD treatment.
▶LL-37PreclinicalLL-37 is the human cathelicidin antimicrobial peptide with dual anti-inflammatory and microbiome-normalizing effects in colitis models; the data are entirely preclinical, making it a candidate concept rather than an IBD therapy.expand
LL-37 is the human cathelicidin antimicrobial peptide with dual anti-inflammatory and microbiome-normalizing effects in colitis models; the data are entirely preclinical, making it a candidate concept rather than an IBD therapy.
▸Full clinical story
As an endogenous host-defense peptide, LL-37 (and its active fragment KR-12) has antibacterial activity plus immunomodulatory effects that reduce mucosal inflammation, and it can shift dysbiotic colonic microbiota — addressing both the inflammatory and microbial contributors to barrier breakdown in IBD.
Evidence is preclinical: LL-37 and KR-12 reduced inflammation (lower macroscopic/ulcer scores and myeloperoxidase) and normalized colonic microbiota, including reductions in E. coli, across TNBS- and DSS-induced mouse colitis models. No human IBD trials exist, so preclinical is the honest grade. Note a nuance — cathelicidin biology in IBD is context-dependent and not uniformly protective in all reports.
Anecdotal community signal: LL-37 is used in some peptide/antimicrobial communities largely for chronic infection and biofilm contexts, with limited direct use for IBD; gut-specific self-reports are sparse. Uncontrolled and not evidence of efficacy.
Context, not a protocol: no established human IBD dose; animal work used intraperitoneal LL-37/KR-12 in the ~1-5 mg/kg range, which does not translate to a human oral or luminal protocol.
LL-37 has concentration-dependent, sometimes pro-inflammatory or cytotoxic effects and its role in IBD tissue is not uniformly beneficial, so more is not necessarily better. Injectable gray-market use for a gut indication has no safety basis; it should not replace evidence-based IBD therapy.
A mechanistically interesting antimicrobial/immunomodulatory peptide with consistent mouse-colitis benefit but no human data and a genuinely double-edged biology; a preclinical concept to monitor, not a treatment to recommend.
▶Low-Dose NaltrexoneEmergingLow-dose naltrexone is a cheap, generally well-tolerated oral option with the most human IBD evidence of any agent on this list, but that evidence is small and mixed, so it sits as a reasonable adjunct in refractory disease rather than a first-line therapy.expand
Low-dose naltrexone is a cheap, generally well-tolerated oral option with the most human IBD evidence of any agent on this list, but that evidence is small and mixed, so it sits as a reasonable adjunct in refractory disease rather than a first-line therapy.
▸Full clinical story
At low doses naltrexone transiently blocks opioid receptors, triggering compensatory endorphin/enkephalin upregulation, and also antagonizes TLR4 on immune cells to blunt inflammatory signaling. Distinct to IBD, it directly accelerates epithelial wound healing and lowers mucosal endoplasmic-reticulum (ER) stress, hitting both the barrier-repair and inflammation arms of the lever.
A prospective open-label study of 47 therapy-refractory IBD patients reported clinical improvement in ~75% and remission in ~26% over 12 weeks, with mechanistic confirmation that naltrexone improved wound healing and reduced ER stress in cells, organoids, and patient mucosa. A Cochrane systematic review of the two randomized trials (46 patients total) found LDN improved clinical and endoscopic RESPONSE versus placebo in adult Crohn's, but clinical/endoscopic REMISSION differences were not statistically significant and overall evidence quality was low due to sparse data. Honest grade: emerging — small controlled human data plus a plausible mechanism, but underpowered.
Anecdotal community signal: LDN has a large, active off-label following in Crohn's/UC and autoimmune circles, typically compounded as capsules or liquid and taken at bedtime, with users reporting reduced flares, less pain, and steroid-sparing; some report sleep disturbance or vivid dreams early on. Widely used, but self-reported and not a substitute for controlled data.
Context, not a protocol: the commonly cited range is 1.5-4.5 mg once daily (often titrated up, frequently dosed at night); pediatric trial work used ~0.1 mg/kg up to 4.5 mg. Requires compounding since commercial naltrexone is 50 mg.
Contraindicated with concurrent opioid analgesics (precipitates withdrawal / blocks analgesia) — a real issue in IBD patients on narcotics for pain. Use caution in significant hepatic impairment; it is an adjunct and should not delay effective anti-inflammatory or biologic therapy in active disease.
The best-evidenced agent here for IBD, yet still only small open-label and underpowered RCT data; a low-risk, low-cost adjunct worth considering in refractory or steroid-dependent patients while setting expectations that remission-level proof is not yet established.
▶alpha-MSHPreclinicalalpha-MSH is the parent melanocortin peptide behind the anti-inflammatory rationale for KPV and melanocortin agonism in IBD; the biology is coherent but support is preclinical, so it is a mechanistic strategy rather than a therapy.expand
alpha-MSH is the parent melanocortin peptide behind the anti-inflammatory rationale for KPV and melanocortin agonism in IBD; the biology is coherent but support is preclinical, so it is a mechanistic strategy rather than a therapy.
▸Full clinical story
Acting through melanocortin receptors (notably MC1R/MC3R) on immune and epithelial cells, alpha-MSH suppresses NF-kB signaling and pro-inflammatory cytokines while rebalancing the cytokine milieu, targeting the inflammatory arm of the lever in the intestinal microenvironment.
Evidence is preclinical: a dedicated melanocortin-system review summarizes multiple mouse colitis models in which alpha-MSH and melanocortin agonism counteract inflammation and cytokine imbalance, and frames melanocortin-interfering molecules as candidate IBD drugs. No human IBD trials of alpha-MSH exist; preclinical is the honest grade.
Anecdotal community signal: alpha-MSH itself is rarely used directly for gut issues; related melanocortin analogs (e.g., melanotan-type peptides) circulate in peptide communities mainly for pigmentation/libido, not IBD. There is minimal condition-specific community use to report, and none of it is evidence of efficacy.
Context, not a protocol: no established human IBD dose for alpha-MSH. Its very short half-life is a key reason downstream fragments (KPV) and stable analogs are pursued instead.
Native alpha-MSH is unstable with a short half-life, limiting practical use, and broad melanocortin activation carries off-target effects (pigmentation, cardiovascular, appetite) that make systemic agonism non-trivial. It is a research strategy, not a treatment, and should not be positioned as clinical care.
The foundational anti-inflammatory melanocortin concept for IBD with solid animal support but no human data; valuable as the rationale for melanocortin-directed agents, not as a deliverable therapy itself.
Matching protocol templates
Browse all →Body recomposition, injury recovery, fat trimming
Skin tightening, collagen repair, wound healing
Gut healing, barrier repair, anti-inflammatory
The platform surfaces evidence, community signal and peer outcomes with enforced cautions. It never decides treatment — the licensed clinician orders labs, writes notes, and prescribes.