Lactiplantibacillus plantarum 299v: A probiotic for IBS and Gut-Brain Axis Support

by Noelle Patno, PhD

L. plantarum 299v is a probiotic globally recognized for having Level 2 evidence for the improvement in severity of abdominal pain in irritable bowel syndrome and a large study preventing C. diffficile-associated diarrhea in antibiotic-treated patients.¹ A new review² on the 30-year anniversary of the isolation of this strain was recently published summarizing the current knowledge on this unique probiotic strain. This article features the main highlights of the reviewed science on probiotic strain Lactobacillus plantarum 299v. 

Characteristics of the strain: ² 

• Plant-derived. L. plantarum 299v belongs to the group of lactic acid bacteria, and these types are commonly found in sauerkraut, brined olives, capers, or sourdough. 
• Gastrointestinal tolerance and survivability. Multiple in vitro and clinical studies have shown that L. plantarum 299v has the ability to survive both the high acidity (low pH) of the stomach as well as the bile of the upper small intestine (high pH).  
• Intestinal colonization. After oral delivery, the strain has been detected in human intestinal mucosa, colonizing both the small and large intestine. One instance was 11 days after humans stopped supplementation. ³ 
• Immune modulation.  L. plantarum 299v stimulated the increase of the transcripts of mucins, which are excreted by goblet cells in the intestine. An increase in the protein MUC4, which is a major component of the glycocalyx, was observed. These glycoproteins protect the surface of the intestinal mucosa, thereby enhancing the gut-associated lymphoid tissue (GALT) innate immunity.  
• Pathogen inhibition. In vitro evidence demonstrated that L. plantarum 299v prevented pathogenic E. coli from adhering to the intestinal epithelial cells, protecting the intestinal barrier, when added before the E. coli.
• Increasing diversity of the intestinal microbiome. L. plantarum 299v consumption has been shown to modify the microbiota and increase diversity in human subjects. 
• Adherence to the intestinal wall and reduced intestinal hyperpermeability. By binding to mannose, L. plantarum 299v prevented E. coli-induced intestinal hyperpermeability in rats and reduced lipopolysaccharide (LPS) translocation into liver of rats.  

Evidence for the usage of L. plantarum 299v in IBS: 

Studies of L. plantarum 299v in irritable bowel syndrome (IBS) have established it as a probiotic for IBS based on the 2017 guidelines of the World Gastroenterology Organisation.¹ These studies include the following: 

• Reduction in gas and pain. A clinical trial of 52 patients with IBS taking 20 billion CFU per day for four weeks resulted in a reduction of flatulence and abdominal pain.⁴ 
• Significant decrease in abdominal severity and frequency in two weeks. A double-blind trial randomized 204 IBS patients to the probiotic at 10 billion CFU or placebo per day for four weeks. By the second week, patients taking the probiotic 299v experienced a significant decrease in frequency and severity of abdominal pain as compared to placebo. 78% of participants had excellent or good effects on their symptoms after consuming the probiotic while only 8% on the placebo had such improvement.⁵   
• One-week efficacy for pain. A randomized controlled trial (RCT) of 40 patients randomized to placebo or 10 billion CFU in liquid for four weeks showed that 70% of those taking L. plantarum 299v resulted in resolution of abdominal pain for all those taking L. plantarum 299v; none reported pain at the end of the four weeks. Strikingly, 95% of the patients taking L. plantarum 299v improved all IBS symptoms including bloating, while only 15% of the placebo consumers experienced improvement.⁶ 

Clostridium difficile infection incidence reduction in hospitalized patients: 

Multiple clinical studies have shown the reduction of C. difficile infections using L. plantarum 299v. The most impressive study showed that in 5,341 subjects, the incidence of C. difficile was significantly reduced during the supplementation of the probiotic strain 299v. Infection incidence was significantly increased during the one-year period after the supplementation ceased, showing the importance of maintaining probiotic supplementation to prevent C. difficile infection.²  

Gut-brain studies: 

The connection between the gut, including the microbiome, and signaling through the immune, nervous, or endocrine systems between the gut and brain, is an area of active research. This “gut-brain” axis may be involved in many disorders, including irritable bowel syndrome as well as others. 

• Cortisol (stress-response hormone) decrease. In a double-blind RCT of 41 students preparing for an upcoming school exam, consuming L. plantarum 299v for two weeks significantly reduced saliva cortisol relative to placebo.⁷ 
• Cognitive performance increase. In a double blind, placebo-controlled trial for eight weeks in subjects with major depression taking selective serotonin reuptake inhibitors, the addition of L. plantarum 299v resulted in a significant improvement in cognitive performance relative to placebo.⁸ 

Iron absorption: 

Another major section of the review article covered multiple studies showing that L. plantarum 299v improved iron status in clinical and animal studies as well as increased iron absorption in multiple clinical studies. When supplemented with iron, the group that also took L. plantarum 299v showed higher serum iron: 

• In healthy women of childbearing age, L. plantarum 299v with 10 mg sucrosomial iron and 15 mg of ascorbic acid for 7 days showed an increase in 11% relative to the group only taking iron and vitamin C, though this was a small, exploratory study without statistical power. 

• In female athletes with low iron stores, but not anemic, supplementing with 20 mg of ferrous fumarate, the group from this RCT with L. plantarum 299v experienced increased plasma ferritin levels by 70% compared to 42% without the probiotic, though not statistically significant (p=0.056).⁹ 
• In 326 healthy, nonanemic pregnant women in a multicenter RCT, 10 billion CFU of L. plantarum 299v significantly mitigated the pregnancy-associated decreases in total body iron, hemoglobin, and serum ferritin levels and showed reduced iron deficiency anemia and iron deficiency prevalence in late pregnancy.¹⁰ 

It is thought that L. plantarum 299v is active in the small intestine to support the reduction of iron and increase the availability of iron from the food matrix.  

Conclusion 

This review demonstrates that L. plantarum 299v is an endogenous intestinal bacteria as well as an effective probiotic, useful for multiple clinical applications. Globally recognized efficacy includes reducing severity of abdominal pain in irritable bowel syndrome and preventing C. diffficile-associated diarrhea in antibiotic-treated patients. While over 170 scientific publications have described L. plantarum 299v, more interesting research is yet to come. More research on its applicability to various populations including major depression and stressful life events are warranted.  

Citations  

1. World Gastroenterology Organisation (WGO). WGO Global Guidelines: Probiotics and Prebiotics. 2017. https://www.worldgastroenterology.org/guidelines/global-guidelines/probiotics-and-prebiotics/probiotics-and-prebiotics-english Accessed March 15, 2019.   
2. Nordström E et al. Benef Microbes. 2021;1–26.   
3. Johansson ML et al. Appl Environ Microbiol. 1993;59(1):15-20. 
4. Nobaek S et al. Am J Gastroenterol. 2000;95:1231-1238. 
5. Ducrotte P et al. World J Gastroenterol. 2012;18:4012-4018.  
6. Niedzielin K et al. Eur J Gastroenterol Hepatol. 2001;13:1143-1147. 
7. Andersson H et al. Int J Microbiology. 2016: 8469018.  
8. Rudzki L et al. Psychoneuroendocrinol. 2019;100: 213-222.
9. Axling U et al. Nutrients. 2020;12(5):1279.  
10. Axling U et al. AOGS. 2021;100(9):1602-1610.  

Noelle Patno, PhD received her PhD in Molecular Metabolism and Nutrition and Masters in Translational Science from the University of Chicago, studying the role of microbial components in intestinal epithelial cell survival related to inflammatory bowel disease. Prior to her graduate studies, Dr. Patno received a chemical engineering degree from Stanford University and worked as an engineer. She has personal experience and interest in preventive nutrition and nutritional therapies for chronic disease, and her current role involves researching and developing probiotics, prebiotics, and other nutritional programs for the promotion of digestive and overall health.