Collagen is the main protein in the extracellular matrix and is present in skin, tendons, cartilage, and bones. In recent years, collagen supplementation has gained significant interest, primarily for its potential benefits to skin and joint health. Collagen peptides have a high safety profile and have been reported to exhibit antioxidant, antihypertensive, antibacterial, anti-inflammatory, and immunomodulatory activities (Ren et al., 2024). Additionally, oral consumption of collagen peptides can affect the composition and metabolism of gut microbiota and may positively influence gastrointestinal homeostasis. This edition highlights four studies examining collagen supplementation on gut health in clinical trials, and cell and animal models. 

Effects of hydrolyzed collagen alone or in combination with fish oil on the gut microbiome in patients with major burns 

Major burns represent one of the most severe forms of trauma and physiological stress. Severe burns can disrupt gut microbiome homeostasis, increase intestinal permeability, and contribute to bacterial translocation. Collagen peptides and omega-3 fatty acids may improve wound healing and the inflammatory response; however, little is known about the restoration of the gut microbiome to improve burn-related complications. This randomized, double-blind, placebo-controlled trial investigated the effects of hydrolyzed collagen, alone or in combination with fish oil, on specific gut microbiome species in patients with major burns. A total of 57 adults aged 18-60 years with 20-45% total body surface area burned were randomized to either consume 1) 40 g of hydrolyzed collagen and 10 mL of sunflower oil; 2) 40 g of hydrolyzed collagen and 10 mL of fish oil; or 3) placebo, divided into two drinks daily, for a duration of two weeks. Gut bacteria were measured using real-time quantitative polymerase chain reaction (qPCR) method at baseline and two weeks. The mean concentration of Bifidobacterium was significantly reduced in the control and collagen groups, compared to baseline values, with no significant change observed in the collagen and omega-3 group. The Firmicutes to Bacteroidetes ratio decreased significantly in the collagen group after supplementation, compared to baseline. No significant changes in the concentration of Lactobacillus, Enterobacteriaceae, and F. prausnitzii were observed between or within the study groups. While two weeks of supplementation with collagen and omega-3 fatty acids in patients with major burns did not result in significant differences in overall bacterial concentrations, the addition of omega-3 fatty acids to collagen prevented a significant reduction in gut Bifidobacterium. Therefore, collagen peptides in combination with omega-3 fatty acids may have therapeutic potential to help prevent negative changes to the gut microbiome in patients with major burns. Future studies are warranted to further investigate the potential clinical benefits of collagen peptides and omega-3 fatty acids in the management of major burns.   

Access to the study: https://www.sciencedirect.com/science/article/abs/pii/S0305417923001699?via%3Dihub 

Reference: Salehi, S., Hosseinzadeh-Attar, M.J., Alipoor, E., Dahmardehei, M., Yaseri, M., Emami, M.R., Siadat, S.D. (2024). Effects of hydrolyzed collagen alone or in combination with fish oil on the gut microbiome in patients with major burns. Burns, 50(2):444-453. https://doi.org/10.1016/j.burns.2023.08.017 

The effects of collagen peptides on exercise-induced gastrointestinal stress: a randomized, controlled trial 

The gastrointestinal barrier serves as a critical physical boundary between the intestinal tract lumen and the body’s circulation and tissues. If the barrier is disrupted, toxins can leak into circulation and initiate a cascade of inflammatory events and gastrointestinal stress such as abdominal pain, stomach cramps, nausea, vomiting, and diarrhea. Moreover, intestinal barrier dysfunction can result from psychological or physiological stress, including strenuous exercise. This randomized, crossover trial examined the effects of collagen peptide supplementation on exercise-induced gastrointestinal stress. A total of 20 moderately well-trained participants were randomized to complete three trials: 1) non-exercise rest trial with no supplementation (REST); 2) exercise trial with 10 g/day collagen peptides; or 3) placebo control supplementation trial. Supplements were administered for a duration of 7 days prior to, and 45 minutes before, a 70-minute run at 70-90% of maximal oxygen uptake (VO2 max). Urinary lactulose and rhamnose (L/R), intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), anti-LPS antibody, monocyte-chemoattractant protein-1 (MCP-1), interleukin (IL)-6 and -8, cortisol, alkaline phosphatase (ALP) and subjective gastrointestinal symptoms were measured before, 10-minutes post, and 2 hours post exercise. There were no differences in heart rate, perceived exertion, thermal comfort, or core temperature during exercise in the collagen peptide and control trials. I-FABP was higher in collagen peptide group and control group compared to the REST group 2 hours post exercise, while LPS increased in the control group compared to the REST group 2 hours post exercise. Anti-LPS antibody decreased in control and collagen peptides compared to REST post exercise. There were no differences in MCP-1, IL-6, and IL-8 between the collagen peptide and control trials, and no differences in L/R or gastrointestinal (GI) symptoms between control and collagen peptides. Overall, collagen peptide supplementation did not modify exercise-induced changes in inflammation, gastrointestinal integrity, or subjective gastrointestinal symptoms. However, LPS levels were higher in control group 2 hours post-exercise. Future studies should explore the effects of collagen peptide supplementation on the gastrointestinal barrier in the absence of exercise and over longer supplementation periods.   

Access to the study: https://pubmed.ncbi.nlm.nih.gov/36370176/ 

Reference: Taylor, G., Leonard, A., Tang, J.C.Y., Dunn, R., Fraser, W.D., Virgilio, N., Prawitt, J., Stevenson, E., & Clifford, T. (2023). The effects of collagen peptides on exercise-induced gastrointestinal stress: a randomized, controlled trial. Eur J Nutr, 62(2):1027-1039. doi: 10.1007/s00394-022-03051-2. 

Effect of a daily collagen peptide supplement on digestive symptoms in healthy women: 2-phase mixed methods study 

Disorders of gut-brain interactions are associated with GI disorders, with irritable bowel syndrome and functional dyspepsia being among the most common disorders. While collagen supplementation has shown to be beneficial for skin, joint, bone, and muscle health, evidence supporting its effects on digestive health remains limited. This two-phase study aimed to investigate the effects of dietary collagen on managing digestive symptoms. Phase 1 of this study used a mixed methods design to explore current attitude and practice among consumers and health care practitioners regarding the use of collagen for managing digestive symptoms such as bloating, as well as perceptions of collagen’s functional benefits. The findings were then used to design Phase 2, an 8-week prospective, open-label, longitudinal, single-arm, digital study. Fourty healthy females were tracked for digestive symptoms, mood, stool, and lifestyle using an app for 2-week baseline period, followed by 8 weeks of consuming 20 g/day of collagen peptides. Participants were required to complete a web-based symptom questionnaire at baseline, Week 2, and Week 8, and participate in two scheduled video interviews. Phase 1 of the trial revealed that consumer awareness of collagen for digestive health is low. Among the dietitians prescribing collagen for patients, the most common dosage was 20 g/day, with notable effects after 6 weeks of intake. In Phase 2 of the study, only 14 of the 40 participants completed the full course of supplementation. Among those who completed the study, 93% (13/14) experienced a reduction in digestive symptoms, including bloating. Overall, the mixed-methods digital study was acceptable for collecting relevant data in real life settings. The use of 20 g/day of collagen peptide supplementation may reduce bloating and improve mild digestive symptoms in otherwise healthy female adults. A randomized, controlled trial is warranted to further evaluate the efficacy of a 6-week collagen peptides supplementation on digestive symptom reduction.   

Access to the study: https://pubmed.ncbi.nlm.nih.gov/35639457/ 

Reference: Abrahams, M., O’Grady, R., & Prawitt, J. (2022). Effect of a daily collagen peptide supplement on digestive symptoms in healthy women: 2-phase mixed methods study. JMIR Form Res, 6(5):e36339. doi: 10.2196/36339. 

Anti-inflammatory activity of collagen peptide in vitro and its effect on improving ulcerative colitis 

Ulcerative colitis (UC) is a major form of Inflammatory Bowel Disease (IBD) that results from a complex interplay among genetic, immune, microbial, and environmental factors. Clinically, UC presents with abdominal pain, distension, mucous, and bloody stools, is often accompanied by weight loss, and carries a markedly increased risk of colon cancer and other serious health complications. Recent studies on collagen peptides from cod skin have exhibited significant anti-tumor, anti-inflammatory, and immunomodulatory properties. This study investigated the anti-inflammatory effects of collagen peptides from cod skin to assess their in vitro anti-inflammatory and in vivo efficacy against UC. The in vitro anti-inflammatory activity of collagen peptides was measured using RAW264.7 cells, and a Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of collagen peptides on cell viability. Inflammation of the cells was induced by LPS, and a low-dose collagen peptide, a medium-dose collagen peptide, and a high-dose collagen peptides were added to the cells. Effects of collagen peptides on nitric oxide (NO) release, cytokine secretion, reactive oxygen species (ROS) content, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) levels, and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) from the cells were measured. Additionally, collagen peptides were examined in 50 male Babl/c mice with dextran sulfate sodium (DSS)-induced UC, and randomly divided to be a control group, a low-dose collagen group (300 mg/kg collagen peptides), high dose group (600 mg/kg collagen peptides), or a positive drug group (100 mg/kg of mesalazine). In mice, the disease activity index score (DAI) which combines body weight changes, stool consistency, and fecal bleeding, and inflammatory markers, protein expression, and intestinal microbiota were evaluated. Collagen peptides inhibited the secretion of pro-inflammatory cytokines and reduced oxidative stress in vitro. In vivo, collagen peptides significantly reduced colonic tissue damage, modulated serum cytokine balance, increased the expression of tight junction proteins, including zonula occludens-1 (ZO-1), Occludin, and Claudin-1, in colon tissue, and enhanced the abundance of beneficial bacteria while reducing harmful bacteria, and restoring microbial balance. In addition, collagen peptides ameliorated colitis in vivo by inhibiting the phosphorylation of the nuclear factor kappa-B/mitogen-activated protein kinase (NF-KB/MAPK) signaling pathway. Based on these findings, collagen peptides may serve as a potential therapeutic option for managing UC; however, further clinical trials are required to confirm these results. 

Access to the study: https://www.nature.com/articles/s41538-024-00367-7 

Reference: Xin, X., Zhou, J., Liu, G., Zhang, M., Li, X., & Wang, Y. (2025). Anti-inflammatory activity of collagen peptide in vitro and its effect on improving ulcerative colitis. Npj Science of Food, 9(1). https://doi.org/10.1038/s41538-024-00367-7 

Bottom Line 

Overall, recent studies highlight the potential of collagen to support gut health. In humans, collagen peptides combined with omega-3 fatty acids prevented reductions in Bifidobacterium in major burn patients, indicating potential therapeutic benefits for maintaining gut microbiome stability. Additionally, collagen peptide supplementation may reduce bloating and improve mild digestive symptoms in healthy participants. Studies in vitro demonstrate that collagen peptides inhibit secretion of pro-inflammatory cytokines and reduce oxidative stress, while in vivo animal models with UC, significantly reduced colonic tissue damage, modulated inflammatory markers, and enhanced abundance of beneficial bacteria. Collagen peptides offer a therapeutic approach to managing gastrointestinal disorders and improving overall gut health, however further human clinical trials are warranted to confirm these findings.  

References 

Abrahams, M., Grady, R., & Prawitt, J. (2022). Effect of a daily collagen peptide supplement on digestive symptoms in healthy women: 2-phase mixed methods study. JMIR Form Res, 6(5):e36339. doi: 10.2196/36339. 

Ren, B., Yue, K., Zhang, Y., & Fu, Y. (2024). Collagen-derived peptides as prebiotics to improve gut health. Current Opinion in Food Science, 55:101123. https://doi.org/10.1016/j.cofs.2024.101123 

Salehi, S., Hosseinzadeh-Attar, M., Alipoor, E., Dahmardehei, M., Yaseri, M., Emami, M., Siadat, S. (2024). Effects of hydrolyzed collagen alone or in combination with fish oil on the gut microbiome in patients with major burns. Burns, 50(2):444-453. https://doi.org/10.1016/j.burns.2023.08.017 

Taylor, G., Leonard, A., Tang, J., Dunn, R., Fraser, W., Virgilio, N., Prawitt, J., Stevenson, E., & Clifford, T. (2023). The effects of collagen peptides on exercise-induced gastrointestinal stress: a randomized, controlled trial. Eur J Nutr, 62(2):1027-1039. doi: 10.1007/s00394-022-03051-2. 

Xin, X., Zhou, J., Liu, G., Zhang, M., Li, X., & Wang, Y. (2025). Anti-inflammatory activity of collagen peptide in vitro and its effect on improving ulcerative colitis. Npj Science of Food, 9(1). https://doi.org/10.1038/s41538-024-00367-7