Last Updated December 11, 2023

 December 11, 2023

Looking to dive deeper into the data on research peptides for gut health? Then keep reading to find out the science behind these potent compounds.

This comprehensive guide ventures into the latest research on peptides with potential benefits for gut health, including:

  • Reducing gut inflammation
  • Improving gut healing and regeneration
  • Protecting against ulcers

Dive into the domains of gut health and peptide research as this article unravels the mechanisms, therapeutic potential, and safety considerations of the most notable peptide-based compounds.

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Top 3 Peptides For Gut Health

Before we get started, let’s review three of the most notable research peptides for gut health.

1. BPC-157

BPC-157 is a synthetic pentadecapeptide formulated in the 1990s and is noted for fostering healing in various tissues, including the gastrointestinal system [1]. It does so by interacting with vasodilators, growth factors, vascularization, and neurotransmitter receptors [2, 3, 4]. BPC-157 has been shown to improve healing post-gastrointestinal surgery (anastomosis healing), ameliorate short bowel syndrome, and protect against ulcers [5, 6].

2. KPV

KPV (lysine-proline-valine) is a C-terminal fragment of alpha-melanocyte-stimulating hormone (alpha-MSH). It may possess anti-inflammatory effects in various tissues, including intestinal cell cultures and models of murine colitis. It is believed to work by reducing immune cell proliferation and inflammatory mediator synthesis. Studies suggest reduced inflammation in models of inflammatory bowel disease (IBD) such as ulcerative colitis [7, 8, 9].

3. VIP

Vasoactive Intestinal Peptide (VIP), a naturally occurring 28-residue peptide of the secretin/glucagon family, is considered to be a neurotransmitter that regulates gut functions like acid secretion and motility. Identified in 1970, it's produced by nerve and immune cells, affecting the gut tract and beyond. Its anti-inflammatory action makes it a potential therapeutic agent in colitis [10].

Peptides For Gut Health

What are Research Peptides?

Peptides are essential organic molecules found in all living organisms, consisting of up to approximately 50 amino acids linked by peptide bonds, usually in a linear arrangement [11].

Peptides may be seen as small proteins, with proteins having longer chains of amino acids [12].

Despite their smaller size, peptides play crucial roles in various physiological processes. Their ability to specifically target receptors has made them a key area of focus in medical research and drug development.

Advances in peptide synthesis have aimed to create analogs of endogenous molecules while improving their stability, selectivity, and efficacy.

There are currently around 60 peptides approved by the United States Food and Drug Administration (FDA) for therapeutic use [13].

In fact, several peptide-based compounds have already been approved by the FDA for therapy in gut-related conditions, such as [14]:

  • Teduglutide, a glucagon-like peptide 2 (GLP-2) receptor agonist approved since 2012 for the treatment of short bowel syndrome and malabsorption.
  • Linaclotide, a guanylate cyclase-2C receptor agonist approved since 2012 for the treatment of irritable bowel syndrome (IBS) with constipation and chronic idiopathic constipation.
  • Plecanatide, a guanylate cyclase-C agonist approved since 2017 for the treatment of chronic idiopathic constipation.

Many more research peptides are under investigation for other indications related to gut health, such as ulcers, inflammation, and healing. Keep reading to find out the most notable ones based on the available data.

Understanding Peptides and Gut Health

Research peptides may have potential to ameliorate various inflammatory conditions that affect the gastrointestinal (GI) tract, ranging from gastritis to ulcerative colitis.

Further, some compounds may also speed up healing at various parts of the GI tract, such as the small intestine (following surgical resection).

Here is a list of potential mechanisms via which peptides may help to improve the aforementioned conditions:

  • Healing peptides such as BPC-157 have been suggested to improve healing of the esophagus/stomach by modulating NO levels. NO is a vasodilator that improves blood flow and upregulates the formation of new blood vessels [2].
  • BPC-157 also appears to help prevent stomach ulcers by interacting with dopamine and adrenaline signaling [4].
  • The anti-inflammatory tripeptide KPV helps reduce inflammation in the digestive system, especially the large intestine (in models of ulcerative colitis), by reducing expression of interleukin-6 (IL-6), IL-12, tumor-necrotizing factor-alpha (TNF-alpha), and interferon-gamma [8].
  • Another peptide called ARA-290 may also exert anti-inflammatory effects on models of colitis by lowering the levels of TNF-alpha [15].

Is Peptide Therapy for Gut Healing Beneficial?

Unfortunately, there is not a great deal of clinical data on whether research peptides are beneficial for gut healing.

As of writing, of the aforementioned compounds, only BPC-157 has entered phase 1 trials as an anti-ulcerative agent in IBD patients; however, the results were never published [16].

Nevertheless, the available preclinical data suggest that peptide therapy may help in several settings, including:

  • Healing of various gastrointestinal anastomoses (surgical resection followed by connecting two segments of the GI tract), including esophagogastric, jejunoileal, colo-colonic, ileoileal, esophagojejunal, esophagoduodenal, and gastrojejunal anastomosis [17].
  • Prevention of gastric ulcers by ameliorating the negative effects of ulcer-inducing agents such as nonsteroidal anti-inflammatory medications (NSAIDs) and potentially suppressing the growth of ulcer-inducing bacteria (Helicobacter pylori) [17, 18].
  • Reducing inflammation in autoimmune conditions such as IBD. For example, several peptides have shown potential for reducing inflammation in ulcerative colitis models [15, 19].

Peptides For Gut Health

Best Peptides For Gut Health and Healing

Below, we outline the most promising peptides for gut health and healing based on the available scientific evidence.


BPC-157, also referred to as Body Protection Compound-157, PL-10, PL 14736, or Bepecin, is a pentadecapeptide developed in the 1990s. It was isolated from a protein present in stomach secretions, but interestingly lacks any similarity to peptide sequences recognized in humans [1].

The peptide is primarily researched for its potential in stimulating healing in various tissues, including the GI tract. This potential is thought to be due to various mechanisms such as modulating vasodilator levels (NO), increasing vascularization, and interacting with neuroreceptors of the alpha-adrenergic and dopaminergic systems [2, 4].

The potential gut healing properties of the peptide have been tested in several preclinical models for a wide range of uses, including:

  • Healing of anastomosis in rats: One study showed improved healing, increased blood supply, and reduced adhesions over 14 days of BPC-157 administration to a murine model of small intestinal anastomosis [20].
  • Improving gut function in short-bowel syndrome: When administered orally and intraperitoneally for four weeks to rats with short-bowel syndrome (after surgical resection), there was an immediate weight gain and increased villus height, crypt depth, and muscle thickness [21].
  • Reducing the risk of gastric ulcers: According to research, BPC-157 may protect stomach cells from ulcers and maintain the integrity of gastric mucosa during exposure to harmful substances such as NSAIDs, haloperidol, and cyclophosphamide [17, 22, 23].

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KPV, aka lysine-proline-valine, is a fragment of the alpha-MSH hormone—more specifically, its C-terminus (alpha-MSH 11-13). Alpha-MSH is a naturally occurring hormone that influences melanogenesis, appetite, sexual desire, and more.

It also appears to have anti-inflammatory properties, specifically attributed to its C-terminus [7].

KPV, in particular, has also been suggested to play a pivotal role in regulating various inflammatory responses such as NF-kB activation, T-cell proliferation, the expression of adhesion molecules, and chemokine receptors [8].

These anti-inflammatory effects have been suggested as beneficial in several laboratory animal models of GI problems. Here’s a breakdown:

  • One murine study reported that KPV improved experimentally-induced ulcerative colitis by targeting inflamed cells, accelerating mucosal healing, and reducing TNF-α levels more effectively than placebo [19].
  • The peptide has demonstrated significant anti-inflammatory effects in two murine IBD models, improving weight recovery and reducing colon inflammation and myeloperoxidase activity independently of melanocortin signaling [24].
  • In two models of mice colitis, KPV was shown to reduce inflammation in gut health by inhibiting NF-kB and MAP kinase pathways via the PepT1 transporter. This led to lower cytokine levels in mice with induced colitis, indicating its potential for treating IBD [9].

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VIP is a 28-residue amino acid peptide that was isolated from porcine duodenum and first characterized in 1970 [10].

VIP is produced by nerve and immune cells and belongs to the secretin/glucagon hormone superfamily. It is widely distributed both inside the GI tract and other organs.

Its physiological roles in gut health include regulating gastric acid secretion, enzyme release from the pancreas, cellular motility, vasodilation, and intestinal contractility.

The therapeutic potential of VIP for gut health includes [10]:

  • In inflammatory bowel diseases (IBD), VIP has been proposed as a biomarker, and its anti-inflammatory properties suggest it may be a therapeutic target.
  • VIP administration has shown both anti-inflammatory and pro-inflammatory effects in laboratory animal models of colitis, depending on dose and context.

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LL-37, also known as human cationic antimicrobial peptide 18 (hCAP18), is the sole human cathelicidin, comprising 37 amino acids.

Originating from the CAMP gene, it is a component of the innate immune response. LL-37 exhibits broad-spectrum antimicrobial properties against bacteria by disrupting their cell membranes [25].

In the gut, LL-37 contributes to mucosal defense. It is expressed in normal gastric tissue and upregulated in response to infections such as Helicobacter pylori, an indication of its role in gastrointestinal immunity.

The peptide's bactericidal action against H. pylori highlights its therapeutic potential, as it could aid in managing infections and associated conditions like gastritis and ulcers.

Given its specificity and increased expression during infection, LL-37 is a promising candidate for targeted therapies aimed at bolstering the gut's defense mechanisms against pathogens [18].

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ARA-290, also known as Cibinetide and helix B surface peptide (HBSP), is a synthetic 11-amino acid peptide. It is designed to replicate a segment of erythropoietin (EPO)—specifically, the helix B region that engages with the innate repair receptor (IRR). Distinct from EPO, the peptide shows a selective affinity for the IRR, activating it without inducing erythropoiesis [26].

Phase 2 studies have put ARA-290 through extensive clinical testing, revealing its safety and effectiveness in ameliorating type 2 diabetes-related complications and alleviating small fiber neuropathy in sarcoidosis [27, 28].

Preclinical studies utilizing mouse models of colonic inflammation have shown that it can suppress macrophage activation and curtail the secretion of inflammatory cytokines like TNF-alpha and IL-1beta [15].

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Peptides Side Effects and Safety

Although some compounds may also be available as oral formulations, peptides for gut health are usually administered as subcutaneous injections. Thus, researchers should keep in mind the common risks associated with injections, such as:

  • Local inflammation
  • Redness at the injection site
  • Pain and swelling

Comprehensive human trials are lacking for the majority of peptides with the potential for gut healing, including BPC-157, KPV, VIP, and LL-37.

Thus, specific information regarding the safety of these compounds is derived primarily from animal studies and preclinical experiments. Nevertheless, the available preclinical research does not report any potential side effects with peptides like BPC-157 and KPV [19, 29].

Moreover, peptides such as VIP and LL-37 are already produced naturally in various parts of the body, namely the gastrointestinal system. Thus, they are not expected to cause any significant side effects.

In short, given the lack of research on peptides for gut health, researchers should stay vigilant for potential unexpected side effects when incorporating these compounds into their work.

Can Peptides Help With Inflammatory Bowel Diseases?

IBS is a term primarily encompassing two chronic conditions: Crohn disease and ulcerative colitis. Both conditions are characterized by prolonged inflammation of the gastrointestinal tract.

Symptoms of IBD can include severe diarrhea, pain, fatigue, and weight loss, and these adverse effects can significantly affect an individual's quality of life.

The exact cause of IBD is not fully understood, but it is thought to involve a combination of genetic predisposition, environmental factors, and an abnormal autoimmune response [30].

Several research peptides are under active investigation for their potential in the management of IBD. For example:

  • BPC-157 is investigated as a potential tool to increase vascularization, improve healing, and reduce malabsorption in IBD [21, 31].
  • KPV, VIP, and ARA-290 may have the potential to reduce inflammation in IBD, which can help ameliorate the damage caused by the autoimmune reaction of the immune system against the GI tract [10, 15, 19].

Gut Health and Research Peptides | Overall

Peptides have emerged as a compelling area of study in the pursuit of advancing gut health. Compounds like BPC-157, KPV, VIP, and LL-37 demonstrate a diverse range of bioactive properties, contributing to the integrity and repair of the gastrointestinal tract.

The scientific exploration of these peptides is an ongoing journey, and acquiring research-grade peptides is a necessity for professionals seeking to unravel the complexities of gut health and develop novel treatments.

Investigators looking to delve into the intricate interactions of peptides and gut health are encouraged to visit our top recommended vendor of research-grade reference materials.


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Scientifically Fact Checked by:

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