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Lactobacillus plantarum--a literature review of therapeutic benefits.


This article reviews scientific literature for evidence of the therapeutic value of Lactobacillus plantarum in treating inflammatory disease and mitigating pathogenic infection.


Connelly P. Lactobacillus plantarum--a literature review of therapeutic benefits. Journal of the Australian Traditional-Medicine Society 2008;14(2):79-82.

Keywords: Lactobacillus plantarum; Probiotic; Intestinal dysbiosis; Complementary medicine.


Inflammatory diseases of the cardiovascular system, the gut (including intestinal dysbiosis such as irritable bowel disease/syndrome (IBD/IBS), Crohn's disease and ulcerative colitis) and low immune function are becoming more common with current highly refined, processed Western diets(1). Probiotics have long been one of the first tools for nutritional treatment of intestinal dysbiosis of all types, but research is now uncovering wider applications for their use.

This paper reviews the literature for Lactobacillus plantarum 299v as a therapeutic agent in a number of conditions, including intestinal dysbiosis, inflammation and pathogenic infection. A Swedish product called Proviva (manufactured by Probi AB, Lund, Sweden) was used in many of the trials cited in the literature. This product is a fruit drink to which has been added a fermented oatmeal gruel which contains L. plantarum 299v(2). It is available in Europe, but is not well-known in Australia.


A search of PUBMED and CINAHL was carried out for papers covering the period 1995 to 2008 reviewing the effects of Lactobacillus plantarum in humans. Murine studies were only considered if the research had strong application to humans, but in general these studies were excluded, along with the studies of L. plantarum use or effects in animals and agriculture. With one exception, full texts of all of the articles were obtained. One paper published in 1993 was included because it was cited as an important reference by many other papers. In all, 29 papers were selected for review. The majority of these studies revealed their funding sources, most of which were from government and educational/research bodies, but eight investigations also disclosed a commercial source of funding, including Probi AB (Lund, Sweden) which provided sources of L. plantarum for two studies. The Danish Dairy Board and the New Zealand Dairy Board were also involved in funding some investigations.


It is clear from clinical research over the last few decades that particular strains of Lactobacillus and Bifidus bacteria have different effects, which can be suited to various disease states(3-7). L. plantarum appears to be an extremely adaptable and useful strain of Lactobacillus that has many modes of operation. In one review article, the authors stated that L. plantarum was the first of the Lactobacillus to have its genome sequenced(8). They reviewed its considerable adaptability within a variety of habitats, such as foods, oral mucosa and the GI tract, and found it capable of synthesising most amino acids de novo via its elaborate proteolytic system.


Like most lactobacilli, L. plantarum is found in a number of strains. One which is commonly used in therapeutic tests and products is L. plantarum 299v, however, research continues into other potentially therapeutic strains of L. plantarum such as LA318 and DSM9843. This paper specifies which strain was used whenever possible, but this information was not always given.

Therapeutic Benefits

Relief from Inflammation and Pain

Beneficial effects of probiotics fall into two categories: recolonisation of the gut with friendly bacteria, or enhancement of the immune system from greater numbers of beneficial bacteria in the gut. In IBD, the mechanisms of action include competition with microbes for receptors on the epithelium; stimulation of gut-associated lymphoid tissue (GALT) and other immune tissues; suppression of pathogenic growth through production of an acid environment; enhancement of the mucosal barrier function and induction of T-cell apoptosis in the lamina propria(9).

There are a number of species of lactobacillus that have beneficial effects on the gut. L. plantarum is one which has showed particular promise in a number of studies. A doubleblind, randomised study of 40 patients who took Proviva for four weeks showed that all of the study group obtained relief from IBS symptoms, with a trend to normalisation of stool frequency in constipation. The authors postulated that these beneficial effects could be due to the unique ability of L. plantarum to catabolise arginine and generate nitric oxide (NO) which may have a positive effect on the motility of the intestines(10).

Similarly, significant findings of reduced pain and flatulence in IBS sufferers were found in another study of 60 patients who also received Proviva for four weeks, though the authors could not offer any real explanation for the improvement(11). Both studies concluded that further research on larger cohorts is required.

Some studies revealed conflicting findings. For example, one uncontrolled, non-blinded, four week clinical trial of 12 patients found that L. plantarum 299v did not improve symptoms in patients with IBS(12). Hydrogen production on the breath was just one of several parameters measured by end expiratory breath samples. Their findings for L. plantarum were not statistically significant compared to placebo.

Regulation of the Mucosal Immune System

An in vitro study in 2004 of inflamed human bowel tissue, gathered from seven patients during resection and treated with L. plantarum 299v, showed production of interleukin-10 (IL-10). The authors found that the ability of L. plantarum to induce human mononuclear lamina propria cells to produce cytokines such as IL-10 may provide this probiotic with a mechanism for reducing excessive inflammation at a mucosal level(13).

More recently, a study of the effects of L. plantarum on Caco-2 cells incubated with tumor necrosis factor-alpha (TNF-alpha) was completed. This study found that induction of epithelial barrier dysfunction and interleukin-8 (IL-8) secretion by TNF-alpha was inhibited by L. plantarum(14).

A study by Naruszewicz is also relevant. The six week study specifically studied the effects of L. plantarum 299v on cardiovascular risks in 36 smokers with no obvious disease symptoms(15). The authors linked the anti-inflammatory effect of L. plantarum with propionic acid, also found in pharmaceutical non-steroidal anti-inflammatory drugs(16), which they found was generated from fermentation of dietary fibre in the colon. In this process, succinate is an intermediate product which is a precursor of propionate(17).

Decreases Fibrinogen and Lipid Levels

A 1997 study of diet supplementation with L. plantarum (Proviva) in 30 male subjects with elevated cholesterol found a statistically significant drop in fibrinogen levels after six weeks, but not the placebo group(18). Cholesterol levels were also lowered in the study group.

The mechanism for lowering fibrinogen appears to be the modulation of immune response, which decreases synthesis of fibrinogen (an acute phase protein). No mechanism was discussed for the drop in cholesterol levels. While the findings are very important to cardiovascular disease, they are also relevant to inflammatory bowel conditions in dysbiosis, as minimisation of inflammation is one of the naturopathic treatments of first choice.

Rapid Inhibition of Many Pathogenic Microbes

L. plantarum's actions have been studied in vitro. It was found that L. plantarum produced antimicrobial compounds which were natural preservatives of very broad applications to the food and agriculture industries(19).

Some in vitro studies had positive findings for treatment of peptic ulcers. Rokka tested seven strains of the L. plantarum group which showed strong anti-Helicobacter pylori activity(20). Another in vitro study tested a group of lactobacilli, including L. plantarum 299v, against six target pathogens which again showed strong anti-Helicobacter activity(21).

Listeria monocytogenes is a food-borne pathogen which is of concern because it grows in various foods at refrigeration temperatures, and in an acid pH environment. A study of the effect of L. plantarum on L. monocytogenes found that L. plantarum produces a bacteriocin which inhibits the pathogen.

The bacteriocin was inactivated by proteolytic enzymes, resistant to heat and stable over a wide pH range. As L. plantarum is produced naturally in many fermented foods, this finding has implications in prevention of food poisoning, and in the natural preservation of foods, particularly in the tropics(22).

Diarrhoea is often caused by Clostridium difficile infection, and can be recurrent due to overgrowth of the pathogen in the gut, particularly after prolonged antibiotic use. L. plantarum 299v, in a randomised, controlled trial for its effects on enhancing short chain fatty acids (SCFAs) in the gut, inhibited C. difficile.

Both groups began with C. difficile-associated diarrhoea. Ten patients received ongoing antibiotics with L. plantarum in a fruit drink, while nine were given the antibiotics and a placebo drink. The treatment group had higher levels of SCFAs and butyrate with no diarrhoea, compared to the placebo group who had a decreasing level of butyrate and continuing recurrence of diarrhoea(17).

Bacterial Translocation Risks Lowered

A prospective randomised trial of 172 patients following major abdominal surgery found that L. plantarum 299v was effective in reducing bacterial translocation(23). Further positive findings showed in an Italian study of pancreatic necrosis in animals, where L. plantarum 299v was effective in reducing microbial translocation in experimental pancreatitis. Treatment with probiotic bacteria seems to be a promising alternative to antibiotic therapy(24).

Excellent Adhesion Characteristics

Studies have shown that L. plantarum is able to adhere to various surfaces where other probiotics do not. L. plantarum has been isolated from jejunal and rectal biopsies as long as 11 days after administration, indicating that this strain may be very well adapted to the human intestine(25,26).

Kinoshita carried out a Biacore analysis of human tissue for adhesion of various lactobacillus strains. Biacore is a Swedish company with technology to measure the binding and adhesion affinity of proteins and other molecules, based on the ability of the biomolecule of interest to interact with a specific binding partner. Of the various strains, L. plantarum LA318 showed the highest adhesion to human colonic mucin(27).

L. plantarum 299v also adheres to gut mucosa. While it adheres in healthy patients, a study of critically ill patients who had undergone antibiotic treatment showed promising results(25). A total of 15 patients completed the controlled study, with 240 cultures performed from biopsies. In the treatment group, no bacterial growth was found, while the control group had growth in five of 32 samples. The study found that repeated administration was required, but that the adherence of L. plantarum to gut mucosa was effective(28).

Adherence to the oral mucosa was also demonstrated. Stjernquist-Desatnik measured the persistence of L. plantarum DSM9843 on the human tonsillar surface, and found that this strain does adhere well to the tonsillar mucosa. This has implications for the treatment of tonsillitis and the control of pathogenic organisms in the oral cavity(29). Recent murine studies have also demonstrated similar effects which may have application to oral peptide delivery(30).

Increased Bioavailability of Iron

L. plantarum has also been found to increase absorption of iron (Fe) from normally low iron bioavailability meals. A study by Bering ran a cross-over trial of 24 healthy women and concluded that L. plantarum 299v increased non-haem Fe absorption from a phytate-rich meal in young women(31). This indicated a specific effect of live L. plantarum 299v and not only an effect of the organic acids.

Their discussion explored the idea that colonisation of the duodenal mucosa by L. plantarum would create a greater concentration of lactic and other organic acids, decreasing pH and the chelation of iron, leading to increased absorption.


L. plantarum has the ability to adhere to the epithelial tissue and the mucosa, to generate anti-inflammatory substances such as propionic acid, to increase IL-10 synthesis and reduce pathogenic infections.

While more research is needed on this and other useful Lactobacillus strains, it is possible to conclude from current and past research that L. plantarum would be a safe and efficacious treatment for various types of intestinal dysbiosis, with beneficial effects to the immune and cardiovascular systems, with promise as a delivery mechanism for other therapeutic substances.


(1) Lopez-Garcia E, Schulze MB, Fung TT, Meigs JB, Rifai N, Manson JE, Hu FB. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. American Journal of Clinical Nutrition 2004;80:1029-1035.

(2) Swedish Nutrition Foundation. Statement concerning evaluation of the scientific documentation behind a product specific health claim: Proviva Fruit Drink with Lactobacillus plantarum 299v. Available from: pdf. Accessed on 17 February 2008.

(3) Shieh Y-H, Chiang B-L, Wang L-H, Liao CK, Gill HS. (2001) Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001. Journal of the American College of Nutrition 2002: 20(2):149-156.

(4) Gill HS, Rutherford KJ, Cross ML. Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes. Journal of Clinical Immunology 2001;21:4.

(5) Gill HS, Rutherford KJ, Cross ML, Gopal PK. Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN0191-3. American Journal of Clinical Nutrition 2001;74:833-839.

(6) Di Marzio L, Russo FP, D'Alo S, Biordi L, Ulisse S, Amicosante G, De Simone C, Grazia Cifone M. Apoptotic effects of selected strains of lactic acid bacteria on a human T leukemia cell line are associated with bacterial arginine deiminase and/or sphingomyelinase activities. Nutrition and Cancer 2001;40(2):185-196.

(7) Liong M-T. Probiotics: a critical review of their potential role as antihypertensives, immune modulators, hypocholesterolemics and perimenopausal treatments. Nutrition Reviews 2007;65(7):316-328.

(8) Claesson MJ, van Sinderen D, O'Toole PW. The genus Lactobacillus--a genomic basis for understanding its diversity. FEMS Microbiology Letters 2007;269:22-28.

(9) Fedorak RN, Madsen KL. Probiotics and the management of inflammatory bowel disease. Inflammatory Bowel Disease 2004;10(3):286-299.

(10) Niedzielen K, Kordecki H, Birkenfeld B. A controlled, doubleblind, randomized study on the efficacy of Lactobacillus plantarus 299V in patients with irritable bowel syndrome. European Journal of Gastroenterology & Hepatology 2001;13:1143-1147.

(11) Nobaek S, Johansson M-L, Molin G, Ahrne S, Jeppsson B. Alteration of intestinal microflora is associated with reduction in abdominal bloating and pain in patients with Irritable Bowel Syndrome. American Journal of Gastroenterology 2000;95(5):1231-1237.

(12) Sen S, Mullan MM, Parker TJ, Woolner JT, Tarry SA, Hunter JO. Effect of Lactobacillus plantarum 299v on colonic fermentation and symptoms of Irritable Bowel Syndrome. Digestive Diseases and Sciences 2002;47(11):2615-2620.

(13) Pathmakantham S, Li CKF, Cowie J, Hawkey CJ. Lactobacillus plantarum 299: beneficial in vitro immunomodulation in cells extracted from inflamed human colon. Journal of Gastroenterology and Hepatology 2004;19:166-173.

(14) Ko JS, Yang JR, Chang JY, Seo JK. Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis facto-a. World Journal of Gastroenterology 2007;13(13):1962-1965.

(15) Naruszewicz M, Johansson M-L, Zapolska-Downar D, Bukowska H. Effect of Lactobacillus plantarum 299v on cardiovascular disease risk factors in smokers. American Journal of Clinical Nutrition 2002;76:1249-1255.

(16) NCI Drug Dictionary: Flurbiprofen. U.S. National Institutes of Health. National Cancer Institute (Accessed 17 Feb 2008). Available from: aspx?CdrID=39245.

(17) Wullt M, Johansson M-L, Odenholt I, Berggren A. Lactobacillus plantarum 299v enhances the concentrations of fecal short-chainfatty acids in patients with recurrent Clostridium difficile-associated diarrhea. Digestive Diseases and Sciences 2007;52: 2082-2086.

(18) Bukowska H, Pieczul-Mroz J, Jastrzebska M, Chelstowski K, Naruszewicz M. Decrease in fibrinogen and LDL-cholesterol levels upon supplementation of diet with Lactobacillus plantarum in subjects with moderately elevated cholesterol. Atherosclerosis 1997;137:437-438.

(19) Niku-Paavola M-L, Laitila A, Mattila-Sandholm T, Haikara A. New types of antimicrobial compounds produced by Lactobacillus plantarum. Journal of Applied Microbiology 1999;86:29-35.

(20) Rokka S, Pihlanto A, Korhonen H, Joutsjoki V. In vitro growth inhibition of Helicobacter pylori by lactobacilli belonging to the Lactobacillus plantarum group. Letters in Applied Microbiology 2006;43:508-513.

(21) Hutt P, Shchepetova J, Loivukene K, Kullisaar T, Mikelsaar M. Antagonistic activity of probiotic lactobacilli and bifidobacteria against entero- and uropathogens. Journal of Applied Microbiology 2006;100:1324-1332.

(22) Olasupo NA. Inhibition of Listeria monocytogenes by Plantaricin NA, an antibacterial substance from Lactobacillus plantarum. Folia Microbiologica 1998;43: 151-155.

(23) Rayes N, Seehover D, Muller AR, Hansen S, Bengmark S, Neuhaus P. Influence of probiotics and fibre on the incidence of bacterial infections following major abdominal surgery--results of a prospective trial. (Translated abstract of article in German). Z. Gastroenterol 2002;40(10):869-876.

(24) Mangiante G, Colucci G, Canepari P, Bassi C, Nicoli N, Casaril A, Marinello P, Signoretto C, Bengmark S. Lactobacillus plantarum reduces infection of pancreatic necrosis in experimental acute pancreatitis. Digestive Surgery 2001;18(1): 47-50.

(25) Johansson M-L, Molin G, Jeppsson B, Nobaek S, Ahrne S, Bengmark S. Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora. Applied and Environmental Microbiology 1993;59(1):15-20.

(26) Ahrne S, Nobaek S, Jeppsson B, Adlerberth I, Wold AE, Molin G. The normal Lactobacillus flora of healthy human rectal and oral mucosa. Journal of Applied Microbiology 1998;85:88-94.

(27) Kinoshita H, Uchida H, Kawai H, Miura K, Shiiba K, Horii A, Saito T. Quantitative evaluation of adhesion of lactobacilli isolated from human intestinal tissues to human colonic mucin using surface plasmon resonance (Biacore assay). Journal of Applied Microbiology 2006;102:116-123.

(28) Klarin B, Johansson M-L, Molin G, Larsson A, Jeppsson B. Adhesion of the probiotic bacterium Lactobacillus plantarum 299v onto the gut mucosa in critically ill patients: a randomised open trial. Critical Care 2005;9:R285-R293.

(29) Stjernquist-Desatnik A, Warfving H, Johansson M-L. Persistence of Lactobacillus plantarum DSM 9843 on human tonsillar surface after oral administration in fermented oatmeal gruel: a pilot study. Acta Otolaryngol Supplt 2000;543:215-219.

(30) Oh Y, Varmanen P, Han XY, Bennett G, Xu Z, Lu T, Palva A. Lactobacillus plantarum for oral peptide delivery. Oral Microbiology and Immunology 2007;22:140-144.

(31) Bering S, Suchdev S, Sjoltov L, Berggren A, Tetens I, Bukhave K. A lactic acid-fermented oat gruel increases non-haem iron absorption from a phytate-rich meal in healthy women of childbearing age. British Journal of Nutrition 2006;96:80-85.

Patrice Connelly B Nat Therapies (SCU), Dip Nutrition is a nutritionist, energetic healer and musician practising in Kilcoy, Qld. PO Box 272, Kilcoy QLD 4515. Telephone (07) 5422 0806,
Summary of the Therapeutic Benefits of Lactobacillus plantarum.

 Action/Mechanism of
 Therapeutic Uses Lactobacillus plantarum

 Benefits immune Stimulates GALT and other lymphoid
 function tissues.

 Creates an acidic environment in the gut
 which is unfriendly to many pathogens.

 Enhances mucosal barrier function.

 Induces T-cell apoptosis in the lamina

 Relief from IBS/IBD Catabolises arginine and generates
 symptoms nitrogen oxide to assist motility of

 Inhibits inflammatory Induces production of IL-10.
 Inhibits epithelial barrier dysfunction.

 Generates propionic acid, a powerful
 anti-inflammatory by fermenting
 dietary fibre in the colon.

 Decreases fibrinogen Modulates immune response so that
 levels production of acute phase proteins is
 not stimulated.

 Rapid inhibition of Competes with pathogens for receptor
 pathogens space on epithelial tissue, depleting the
 space for pathogens to grow.

 Shows strong anti-Helicobacter pylori

 Produces a bacteriocin which inhibits
 Listeria monocytogenes.

 Reduces Clostridium difficile-associat-
 ed diarrhoea by stimulating butyrate
 and short chain fatty acid production.

 Lowers risks of bacterial Competes with pathogens for receptor
 translocation space on epithelial tissue, depleting the
 space for pathogens to grow.

 Potential delivery Strong ability to adhere to various bod-
 mechanism for ily surfaces including oral and gut
 therapeutic mucosa.

 Increases absorption of Colonisation of duodenum increases
 iron from low Fe- lactic and organic acids and decreases
 bioavailability meals Fe chelation to assist absorption of iron.
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Author:Connelly, Patrice
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Geographic Code:8AUST
Date:Jun 1, 2008
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