Peptides for Gut Health – Larazotide, Apigenin, BPC 157, KPV, Butyrate, L-Glutamine

Peptides for Gut Health – Larazotide, Apigenin, BPC 157, KPV, Butyrate, L-Glutamine

Our gut is sometimes called our second brain, and for good reason. First, our enteric nervous system (ENS), which is located throughout our gastrointestinal tract, “helps control our same chemicals and cells as the brain to help us digest and to alert the brain when something is amiss” (Ruder, 2017). Second, the gut can act independently as if it has a mind of its own: “due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system” (Fleming II et al., 2020).  The enteric nervous system is part of the autonomic nervous system, which also includes the sympathetic (flight, fright or freeze) and the parasympathetic (rest and digest) nervous systems. These autonomic nervous systems control the functions that our body does automatically, such as our heartbeat, metabolism, digestion, urinary and bowel movements, and breathing. The gut/ brain axis is the reason we get butterflies in our stomach when we see our crush, lose our appetite when we are sad, or go to the bathroom when we are nervous. We generally “trust our gut” and sometimes have to do a “gut check” to make sure that we are correct in our assumptions. When someone exhibits bravery, we say they “have guts” and when someone is upset, they are “gutted.” From being an idiom, to a second brain, or just digesting our lunch, guts are super important!

The health of our gut depends upon the food we eat, as well as our stress levels and sleep hygiene. An unhealthy gut can exhibit symptoms such as nausea, vomiting, abdominal pain, distention, constipation, diarrhea, or illnesses such as ulcers, Irritable Bowel Syndrome (IBS), Crohn’s Disease, and Ulcerative Colitis. Ways to improve gut health including eating foods that are high in fiber such as fruits, vegetables and nuts; foods with probiotics such as yogurt and fermented food like sauerkraut, and kimchi; foods with prebiotics such as garlic, onions, bananas and oats; foods high in omega-3 fatty acids such as fatty fish, chia seeds, and walnuts; healthy spices such as ginger and tumeric; and healing drinks such as bone broth and peppermint tea. However, “if we are to gain the nutritional benefits from food, they are to be properly absorbed, digested and eliminated” (Murray & Pizzorno, 2012). One way to help our gut function optimally and lessen the burden of illness is through peptides such as Larazotide, Apigenin, BPC-157, KPV, Butyrate, and L-Glutamine.

Larazotide, also known as Larazotide acetate (LA), is a synthetic peptide that is made up of “a single-chain peptide of eight amino acids that acts as a tight junction regulator to restore intestinal barrier function” (Slifer et al., 2021). Larazotide is currently being studied for illnesses of intestinal permeability and is the subject of a late-phase clinical trial for patients with celiac disease, whose intestinal barrier is compromised. The mechanism of action is due to the fact that Larazotide acts as an antagonist against zonulin, which is a protein in the small intestine that affects gut permeability. Zonulin creates spaces in the “junctions” of the gut and by tightening up these spaces, intestinal barrier function can be restored.

Apigenin is a naturally occurring flavonoid that is found in plants and taken commonly as a supplement. Flavonoids are important because they “act as free-radical scavengers and antioxidants, exhibiting anti-mutagenic, anti-inflammatory, and antiviral effects…[and] are able to reduce plasma levels of low-density lipoproteins, inhibit platelet aggregation, and reduce cell proliferation.” (Salehi, 2019). Due to their extraordinary nature, these small molecules can help prevent cancerous cells from forming as it “induces apoptosis of various cancer cell lines and has potent antiinflammatory activity by inhibiting a pathway resulting in NF-κB activation” (Arango et al., 2013). When it comes to the gut, apigenin “affects Enterococcus caccae cell wall/membrane synthesis and increases the incidence of protein misfolding… Bacteroides galacturonicus growth was also inhibited by apigenin…[and] apigenin promoted overall growth and diversity, lowered Firmicutes to Bacteroidetes ratio, and promoted production of short chain fatty acids, including butyrate, which is associated with health” (Wang et al., 2017).  The positive impact that apigenin has on the guts then is that it promotes a healthy microbiome, repairs intestinal genes, and acts as an anti-inflammatory.

BPC 157 is an acronym for “Body Protecting Compound 157” and is a naturally occurring 15-chain amino acid peptide that offers gastric protection; helps heals tissues, ligaments, bones and muscles; and is both neuroprotective and cardioprotective (Seeds, 2020). It is a “membrane stabilizer and counteracts gut-leaky syndrome…has profound cytoprotective activity…and specifically [controls] the VEGF [vascular endothelial growth factor] and NO [nitric oxide] pathways, in particular the prostaglandin pathway” (Sikiric et al, 2022). Therefore it not only helps the gut lining to function as it should, but it also repairs any previous damage and helps prevent future corruption. 

KPV, also known as Lysine-proline-valine, is “a naturally occurring tripeptide [that] has been shown to attenuate the inflammatory responses of colonic cells…[and] exerts its anti-inflammatory function inside cells, where it inactivates inflammatory pathways (Xiao et al., 2017). In clinical studies of Ulcerative Colitis, it helps both with healing the mucus lining of the colon as well as alleviating inflammation. The mechanism of action has been determined that “KPV inhibits the activation of NF-kappaB and MAP kinase inflammatory signaling pathways, and reduces pro-inflammatory cytokine secretion…acts via PepT1 expressed in immune and intestinal epithelial cells…..[and] reduces the incidence of DSS- and TNBS-induced colitis indicated by a decrease in pro-inflammatory cytokine expression” (Dalmasso et al., 2008). Additional studies suggest its potency in wound healing as well, which can further support gut health.

Butyrate or Butyric acid, is a short-chain fatty acid that your body naturally produces when it breaks down fiber. In the intestines, “butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility” (Canani et al., 2011).  Outside the intestines, “butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke” (Canani et al., 2011). The mechanisms of action for butyrate are due to the fact that it helps regulate gene expression, supports intestinal homeostasis and energy metabolism, and is an anti-inflammatory (Liu et al., 2018).

L-Glutamine, also known as Glutamine, is the most abundant amino acid in the body and a very common supplement that supports the gut microbiota and immunity. It helps the intestinal endothelium and “promotes enterocyte proliferation, regulates tight junction proteins, suppresses proinflammatory signaling pathways, and confers protection against apoptosis and cellular stresses during normal and pathological conditions” (Perna et al., 2018). L-Glutamine is well studied and one of the most beneficial amino acids that exists.  Its mechanism of action is due to the fact that it assists with “maintenance of intestinal mucosal integrity, modulation of inflammatory response, nucleotide biosynthesis, energy metabolism, and stimulation of immunity” (Perna et al., 2018). Its overall effects on the gut include regulating the GI microbiome, improving the functions of the intestines, and reducing constipation.

If a healthy diet and stress management practices such as yoga, meditation, and deep breathing exercises still leave you with gut issues, these peptides may be just what you need to help restore health and balance to your digestive system.


Arango, D., Morohashi, K., Yilmaz, A., Kuramochi, K., Parihar, A., Brahimaj, B., Grotewold, E., & Doseff, A. I. (2013). Molecular basis for the action of a dietary flavonoid revealed by the comprehensive identification of apigenin human targets. Proceedings of the National Academy of Sciences of the United States of America, 110(24), E2153–E2162.

Canani, R. B., Costanzo, M. D., Leone, L., Pedata, M., Meli, R., & Calignano, A. (2011). Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World journal of gastroenterology, 17(12), 1519–1528.

Dalmasso, G., Charrier-Hisamuddin, L., Nguyen, H. T., Yan, Y., Sitaraman, S., & Merlin, D. (2008). PepT1-mediated tripeptide KPV uptake reduces intestinal inflammation. Gastroenterology, 134(1), 166–178.

Fleming II, Ehsan, L., Moore, S. R., & Levin, D. E. (2020). The Enteric Nervous System and Its Emerging Role as a Therapeutic Target. Gastroenterology research and practice, 2020, 8024171.

Liu, H., Wang, J., He, T., Becker, S., Zhang, G., Li, D., & Ma, X. (2018). Butyrate: A Double-Edged Sword for Health?. Advances in nutrition (Bethesda, Md.), 9(1), 21–29.

Murray, M. T., &  Pizzorno, J. E., (2012). The encyclopedia of natural medicine. New York, NY: Atria Books.

Ruder , D. (2017). The gut and the brain. Harvard Medical School.,brain%20when%20something%20is%20amiss. 

Perna, S., Alalwan, T. A., Alaali, Z., Alnashaba, T., Gasparri, C., Infantino, V., Hammad, L., Riva, A., Petrangolini, G., Allegrini, P., & Rondanelli, M. (2019). The Role of Glutamine in the Complex Interaction between Gut Microbiota and Health: A Narrative Review. International journal of molecular sciences, 20(20), 5232.

Salehi, B., Venditti, A., Sharifi-Rad, M., Kręgiel, D., Sharifi-Rad, J., Durazzo, A., Lucarini, M., Santini, A., Souto, E. B., Novellino, E., Antolak, H., Azzini, E., Setzer, W. N., & Martins, N. (2019). The Therapeutic Potential of Apigenin. International journal of molecular sciences, 20(6), 1305.

Seeds, W. A. (2020). The peptide protocols: A handbook for practitioners. Spire Institute.

Sikiric, P., Skrtic, A., Gojkovic, S., Krezic, I., Zizek, H., Lovric, E., Sikiric, S., Knezevic, M., Strbe, S., Milavic, M., Kokot, A., Blagaic, A. B., & Seiwerth, S. (2022). Cytoprotective gastric pentadecapeptide BPC 157 resolves major vessel occlusion disturbances, ischemia-reperfusion injury following Pringle maneuver, and Budd-Chiari syndrome. World journal of gastroenterology, 28(1), 23–46.

Slifer, Z. M., Krishnan, B. R., Madan, J., & Blikslager, A. T. (2021). Larazotide acetate: a pharmacological peptide approach to tight junction regulation. American journal of physiology. Gastrointestinal and liver physiology, 320(6), G983–G989.

Wang, M., Firrman, J., Zhang, L., Arango-Argoty, G., Tomasula, P., Liu, L., Xiao, W., & Yam, K. (2017). Apigenin Impacts the Growth of the Gut Microbiota and Alters the Gene Expression of Enterococcus. Molecules (Basel, Switzerland), 22(8), 1292.

Xiao, B., Xu, Z., Viennois, E., Zhang, Y., Zhang, Z., Zhang, M., Han, M. K., Kang, Y., & Merlin, D. (2017). Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Molecular therapy : the journal of the American Society of Gene Therapy, 25(7), 1628–1640.

About the author: Mary Genevieve Carty, MS, MHEd holds Masters degrees in Complementary and Integrative Health as well as Higher Education and is currently a doctoral student in Health Science at George Washington University’s College of Medicine and Health Science.  She is passionate about holistic health and wellness, and has additional training in teaching, Reiki, and Tapping/ Emotional Freedom Technique. Her research interests include resiliency, psychoneuroimmunology, neuroplastic pain, placebo/ nocebo effect, and bioenergy therapies.  The views she expresses are her own, and do not reflect any affiliation.

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Medically reviewed by Dr. Stephen Matta, DO, MBA CAQSM and Mary Anne Matta, MS, MA, LAC

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