Contents
  1. The strain at a glance
  2. Mechanism of action
  3. Composition and production
  4. Research overview
  5. Publications
  6. Contact

DSM 14241

Limosilactobacillus fermentum ME-3®

A probiotic strain of human origin with a complete glutathione system

Scientific information on the ME-3® strain for formulators and for R&D, quality and regulatory professionals: identity, mechanism of action, production and the published research.

Pale freeze-dried culture powder on a dark glass surface, close-up in soft side light
Publications
25
Human clinical studies
13
University of Tartu, Estonia
Human origin

Identity

The strain at a glance

Species
Limosilactobacillus fermentum (formerly Lactobacillus fermentum; genus reclassified in 2020)
Strain
ME-3, deposited at the DSMZ culture collection as DSM 14241
Origin
isolated in 1995 at the University of Tartu, Estonia, from the intestinal microbiota of a healthy one-year-old child
Safety
L. fermentum is on the EFSA list of microorganisms with Qualified Presumption of Safety (QPS). No transferable antibiotic resistance identified
EU regulatory status
not a novel food (VF Bioscience statement available on request)
Intellectual property
patented strain; US Patent 9,974,817; European Patent EP2943210B1; Japanese Patent 6484561
Grades
10 × 109 CFU/g for food applications; 100 × 109 CFU/g for dietary supplements; tyndallized grade available on request
Stability
24 months at room temperature in finished capsule products
Research
more than 20 publications since 2003, including randomised controlled trials in humans

Mechanism

Mechanism of action

Rod-shaped bacterial cells glowing blue on a dark background, with a small molecular model in the distance

A complete glutathione system.

ME-3 is one of the few probiotic strains in which a complete glutathione system has been described: the strain synthesises glutathione, takes it up from its environment and recycles it through glutathione peroxidase and glutathione reductase activity (Kullisaar 2010, in vitro). It also expresses manganese superoxide dismutase. In a screening study on more than 200 lactobacilli and bifidobacteria strains, ME-3 showed the highest antioxidant activity (Mikelsaar 2009, in vitro).

Antioxidant markers in humans.

In human studies, intake of ME-3 was associated with changes in blood markers of antioxidant status: total antioxidative activity and status (TAA, TAS), the glutathione redox ratio, oxidised LDL and paraoxonase activity (Kullisaar 2003; Songisepp 2005; Kullisaar 2011). After 14 days of ME-3-fermented kefir, the serum signal corresponding to glutathione increased in an uncontrolled study (Rehema 2015).

Antimicrobial activity.

ME-3 produces organic acids and showed high activity against Salmonella, Shigella sonnei and Helicobacter pylori strains in vitro (Hütt 2006; Mikelsaar 2008).

Gut survival.

ME-3 tolerates gastric acidity and bile and adheres to intestinal mucosa (Mikelsaar 2009).

Intestinal barrier.

In an intestinal epithelial cell model, ME-3 prevented the increase in paracellular permeability caused by irinotecan or bacterial lipopolysaccharide and preserved tight-junction proteins (De Gregorio 2023, in vitro).

Production

Composition and production

ME-3 is produced by controlled fermentation and freeze-drying and supplied as a powder standardised on viable count, with maltodextrin as carrier. Two concentrations are available: 10 × 109 CFU/g for food applications and 100 × 109 CFU/g for dietary supplements. A tyndallized grade is available on request. Production in an FSSC 22000-certified facility.

Stability.

In finished capsule products, ME-3 is stable for 24 months at room temperature. Storage conditions and shelf life of the powder: see technical data sheet.

ME-3 has been used in capsules, powder sachets and fermented dairy products (kefir, yoghurt, fermented goat milk). In human studies, daily intakes ranged from about 109 CFU (capsule studies) to 4 × 1010 CFU (kefir studies). Recommended daily dose for capsule products is 6 to 8 × 109 CFU/day. Technical data sheet, certificate of analysis and regulatory statements on request.

Stainless steel bioreactor in a clean room, with a sight glass in the lid, valves and piping

Research

Research overview

Studies are grouped by topic. The evidence type is given for each: human, animal or in vitro. Full references are listed under Publications.

Antioxidant status

  • Human

Controlled studies in healthy adults found higher total antioxidative activity and lower markers of lipid and lipoprotein oxidation after 3 weeks of ME-3 in fermented goat milk or capsules (Kullisaar 2003; Songisepp 2005). Comparable marker changes were measured in skin and blood in a controlled study in adults with mild-to-moderate atopic dermatitis (Kaur 2008), and with a multi-strain synbiotic containing ME-3 in adults colonised with H. pylori (Hütt 2009).

Blood lipids and lipoprotein oxidation

  • Human

In a randomised placebo-controlled trial in 100 healthy adults, kefir with ME-3 lowered postprandial oxidised LDL, triglycerides and urinary 8-isoprostanes (Kullisaar 2011). In a randomised controlled trial in 164 adults with borderline-high LDL cholesterol and/or triglycerides, 8 weeks of kefir with ME-3 (8 × 109 CFU/day) reduced LDL-C by 5%, oxidised LDL by 6% and triglycerides by 17%, with significant differences versus control (Mikelsaar 2015).

Combination product

Studies with Reg'Activ Cholesterol, a formula combining ME-3 with other ingredients, report improvements in lipid, oxidised LDL and HbA1c markers (Kullisaar 2016; Rehema 2019; Kullisaar 2019).

Gut microbiota

  • Human

In a double-blind placebo-controlled pilot, 8 weeks of kefir with ME-3 increased the richness and diversity of intestinal lactobacilli and overall microbiota diversity (Sepp 2018). Total faecal lactobacilli also increased after 3 weeks of ME-3 intake (Songisepp 2005).

Intestinal barrier and infection models

  • In vitro
  • Animal

In Caco-2 cell models, ME-3 prevented irinotecan- and LPS-induced barrier disruption and reduced pro-inflammatory cytokine release (De Gregorio 2023). In mice infected with Salmonella Typhimurium, ME-3 given alone reduced oxidative damage in the gut mucosa but not the infection itself (Truusalu 2004). Combined with the antibiotic ofloxacin, it improved pathogen clearance and reduced liver and spleen granulomas (Truusalu 2008; Truusalu 2010).

Glycation and metabolic markers

  • Animal

In diabetic db/db mice, 12 weeks of ME-3 reduced weight gain, improved glucose tolerance, lowered glycation products in kidneys and lungs and reduced liver fat accumulation (Guilbaud 2020).

Laboratory glassware and a pipette rack on a dark bench, shallow depth of field

Evidence

Publications

Human studies 13

  1. 2003

    Antioxidative probiotic fermented goats' milk decreases oxidative stress-mediated atherogenicity in human subjects

    Kullisaar T, et al. British Journal of Nutrition 90(2):449-456

    Human, controlled pilot
  2. 2005

    Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers

    Songisepp E, et al. Nutrition Journal 4:22

    Human, open placebo-controlled + RCT
  3. 2008

    Successful management of mild atopic dermatitis in adults with probiotics and emollients

    Kaur S, et al. Central European Journal of Medicine 3(2):215-220

    Human, controlled pilot
  4. 2008

    Double benefit claims for anti-microbial and anti-oxidative probiotic

    Mikelsaar M, et al. Microbial Ecology in Health and Disease 20:184-188

    In vitro + human RCT crossover (synbiotic)
  5. 2009

    Effects of a synbiotic product on blood antioxidative activity in subjects colonized with Helicobacter pylori

    Hütt P, et al. Letters in Applied Microbiology 48(6):797-800

    Human, RCT crossover (synbiotic)
  6. 2011

    An antioxidant probiotic reduces postprandial lipemia and oxidative stress

    Kullisaar T, et al. Central European Journal of Biology 6(1):32-40

    Human, RCT
  7. 2015

    Regulation of plasma lipid profile by Lactobacillus fermentum (probiotic strain ME-3 DSM14241) in a randomised controlled trial of clinically healthy adults

    Mikelsaar M, et al. BMC Nutrition 1:27

    Human, RCT
  8. 2015

    Proteomic proof that a probiotic elevates glutathione level in human serum

    Rehema A, et al. Open Life Sciences 10

    Human, uncontrolled
  9. 2016

    The use of probiotic L. fermentum ME-3 containing Reg'Activ Cholesterol supplement for 4 weeks has a positive influence on blood lipoprotein profiles and inflammatory cytokines: an open-label preliminary study

    Kullisaar T, et al. Nutrition Journal 15(1):93

    Human, open-label pilot Combination product
  10. 2018

    The effect of Lactobacillus fermentum ME-3 on the intestinal microbiota and urine polyamine content: a double-blind placebo-controlled pilot trial

    Sepp E, et al. Journal of Functional Foods 48:430-438

    Human, double-blind placebo-controlled pilot
  11. 2019

    Multi-targeted prevention of cardiovascular disease risk factors with Reg'Activ Cholesterol food supplement

    Rehema A, et al. EC Nutrition 14(11):101-110

    Human, RCT Combination product
  12. 2019

    The Reg'Activ Cholesterol positive effects in asymptomatic volunteers with borderline values of cardio-metabolic risk factors are sustainable in long-term run

    Kullisaar T Research Open - Endocrinology, Diabetes and Metabolism Journal 3(2)

    Human, long-term follow-up Combination product
  13. 2021

    Improvement of metabolic syndrome status by risk factors modifications with probiotic

    Kullisaar T, Rehema A Open Journal of Case Reports 2:123

    Human, case report Combination product

Animal studies 4

  1. 2004

    The influence of antibacterial and antioxidative probiotic lactobacilli on gut mucosa in a mouse model of Salmonella infection

    Truusalu K, et al. Microbial Ecology in Health and Disease 16:180-187

    Animal
  2. 2008

    Eradication of Salmonella Typhimurium infection in a murine model of typhoid fever with the combination of probiotic Lactobacillus fermentum ME-3 and ofloxacin

    Truusalu K, et al. BMC Microbiology 8:132

    Animal
  3. 2010

    Immunological, antioxidative, and morphological response in combined treatment of ofloxacin and Lactobacillus fermentum ME-3 probiotic in Salmonella Typhimurium murine model

    Truusalu K, et al. APMIS 118(11):864-872

    Animal
  4. 2020

    The effect of Lactobacillus fermentum ME-3 treatment on glycation and diabetes complications

    Guilbaud A, et al. Molecular Nutrition & Food Research 64

    Animal

In vitro studies 4

  1. 2001

    Characterisation and differentiation of lactobacilli by lectin typing

    Annuk H, et al. Journal of Medical Microbiology 50(12):1069-1074

    In vitro
  2. 2006

    Antagonistic activity of probiotic lactobacilli and bifidobacteria against entero- and uropathogens

    Hütt P, et al. Journal of Applied Microbiology 100(6):1324-1332

    In vitro
  3. 2010

    Complete glutathione system in probiotic Lactobacillus fermentum ME-3

    Kullisaar T, et al. Prikladnaia Biokhimiia i Mikrobiologiia 46(5):527-531 (Applied Biochemistry and Microbiology)

    In vitro, mechanistic
  4. 2023

    Protective effect of Limosilactobacillus fermentum ME-3 against the increase in paracellular permeability induced by chemotherapy or inflammatory conditions in Caco-2 cell models

    De Gregorio A, et al. International Journal of Molecular Sciences 24(7):6225

    In vitro

Reviews and background 4

  1. 1997

    Intestinal microflora of Estonian and Swedish infants

    Sepp E, et al. Acta Paediatrica 86(9):956-961

    Human, observational (background)
  2. 2008

    Probiotics, oxidative stress, inflammation and diseases

    Kullisaar T, et al. Proceedings of the 4th European Congress on Food

    Conference proceedings
  3. 2009

    Lactobacillus fermentum ME-3 - an antimicrobial and antioxidative probiotic

    Mikelsaar M, Zilmer M Microbial Ecology in Health and Disease 21(1):1-27

    Review (strain monograph)
  4. 2016

    Biodiversity of intestinal lactic acid bacteria in the healthy population

    Mikelsaar M, et al. Advances in Experimental Medicine and Biology 932:1-64

    Review

Contact

Technical documentation, samples and commercial enquiries

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